Instruction: Extract chemical and disease entities from the following text.

Input: Naloxone reverses the antihypertensive effect of clonidine. In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.

Output: Chemical/Disease Entities: Naloxone (Chemical), clonidine (Chemical), hypertensive (Disease), clonidine (Chemical), nalozone (Chemical), hypotensive (Disease), alpha-methyldopa (Chemical), naloxone (Chemical), Naloxone (Chemical), hypertensive (Disease), clonidine (Chemical), [3H]-naloxone (Chemical), naloxone (Chemical), clonidine (Chemical), [3H]-dihydroergocryptine (Chemical), hypertensive (Disease), naloxone (Chemical), clonidine (Chemical), clonidine (Chemical), alpha-methyldopa (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Lidocaine-induced cardiac asystole. Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.

Output: Chemical/Disease Entities: Lidocaine (Chemical), cardiac asystole (Disease), lidocaine (Chemical), depression (Disease), bradyarrhythmias (Disease), lidocaine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Suxamethonium infusion rate and observed fasciculations. A dose-response study. Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.

Output: Chemical/Disease Entities: Suxamethonium (Chemical), fasciculations (Disease), Suxamethonium chloride (Chemical), Sch (Chemical), tetanic (Disease), Sch (Chemical), Fasciculations (Disease), fasciculation (Disease), fasciculation (Disease), twitch (Disease), tetanus (Disease), Fasciculations (Disease), fasciculation (Disease), fasciculation (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine). Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.

Output: Chemical/Disease Entities: Galanthamine hydrobromide (Chemical), scopolamine (Chemical), Hyoscine (Chemical), Galanthamine hydrobromide (Chemical), scopolamine (Chemical), hyoscine (Chemical), overdosage (Disease), physostigmine (Chemical), scopolamine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats. Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Output: Chemical/Disease Entities: lithium (Chemical), chronic renal failure (Disease), lithium (Chemical), nephropathy (Disease), renal failure (Disease), lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), lithium (Chemical), Li (Chemical), Lithium (Chemical), proteinuria (Disease), hypertension (Disease), glomerulosclerosis (Disease), renal failure (Disease), creatinine (Chemical), lithium (Chemical), Li (Chemical), Li (Chemical), nephropathy (Disease), proteinuria (Disease), hypertension (Disease), chronic renal failure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin. Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.

Output: Chemical/Disease Entities: Crohn's disease (Disease), fusidic acid (Chemical), cyclosporin (Chemical), cyclosporin (Chemical), Crohn's disease (Disease), fusidic acid (Chemical), Crohn's disease (Disease), Fusidic acid (Chemical), fusidic acid (Chemical), nausea (Disease), fusidic acid (Chemical), Crohn's disease (Disease), fusidic acid (Chemical), inflammatory bowel disease (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers. The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.

Output: Chemical/Disease Entities: myocardial injury (Disease), cocaine (Chemical), cocaine (Chemical), schizophrenic (Disease), cocaine (Chemical), myocardial injury (Disease), myocardial infarction (Disease), ischemia (Disease), bundle branch block (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Sulpiride-induced tardive dystonia. Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.

Output: Chemical/Disease Entities: Sulpiride (Chemical), tardive dystonia (Disease), Sulpiride (Chemical), antidepressant (Chemical), sulpiride (Chemical), tardive dyskinesia (Disease), parkinsonism (Disease), dystonia (Disease), sulpiride (Chemical), sulpiride (Chemical), tardive dystonia (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine. During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.

Output: Chemical/Disease Entities: desferrioxamine (Chemical), desferrioxamine (Chemical), audiovisual toxicity (Disease), Visual toxicity (Disease), dyschromatopsy (Disease), a loss of visual acuity (Disease), pigmentary retinal deposits (Disease), Auditory toxicity (Disease), neurosensorial hearing loss (Disease), Desferrioxamine (Chemical), hearing loss (Disease), toxicity (Disease), desferrioxamine (Chemical), aluminium (Chemical), audiovisual toxicity (Disease), desferrioxamine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Myasthenia gravis presenting as weakness after magnesium administration. We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.

Output: Chemical/Disease Entities: Myasthenia gravis (Disease), magnesium (Chemical), neuromuscular disease (Disease), quadriplegic (Disease), magnesium (Chemical), preeclampsia (Disease), magnesium (Chemical), magnesium (Chemical), postsynaptic neuromuscular blockade (Disease), acetylcholine (Chemical), paralysis (Disease), magnesium (Chemical), myasthenia gravis (Disease), magnesium (Chemical), disorder of neuromuscular transmission (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication. Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.

Output: Chemical/Disease Entities: Chloroacetaldehyde (Chemical), cyclophosphamide (Chemical), ifosfamide (Chemical), chloroacetaldehyde (Chemical), CAA (Chemical), CAA (Chemical), CAA (Chemical), bladder damage (Disease), CAA (Chemical), mesna (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Source of pain and primitive dysfunction in migraine: an identical site? Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.

Output: Chemical/Disease Entities: pain (Disease), migraine (Disease), migraine (Disease), nitroglycerin (Chemical), migraine (Disease), nitroglycerin (Chemical), migraine (Disease), nitroglycerin (Chemical), migraine (Disease), migraine (Disease), nitroglycerin (Chemical), pain (Disease), migraine (Disease), migraine (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Clotiazepam-induced acute hepatitis. We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.

Output: Chemical/Disease Entities: Clotiazepam (Chemical), hepatitis (Disease), hepatitis (Disease), extensive hepatocellular necrosis (Disease), clotiazepam (Chemical), thienodiazepine (Chemical), Clotiazepam (Chemical), benzodiazepines (Chemical), clotiazepam (Chemical), hepatitis (Disease), clotiazepam (Chemical), hepatitis (Disease), hepatotoxicity (Disease), clotiazepam (Chemical), benzodiazepines (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Arterial hypertension as a complication of prolonged ketoconazole treatment. Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.

Output: Chemical/Disease Entities: hypertension (Disease), ketoconazole (Chemical), Cushing's syndrome (Disease), ketoconazole (Chemical), hypertension (Disease), cortisol (Chemical), ketoconazole (Chemical), hypertension (Disease), deoxycorticosterone (Chemical), 11-deoxycortisol (Chemical), deoxycorticosterone (Chemical), 11-deoxycortisol (Chemical), aldosterone (Chemical), ketoconazole (Chemical), hypertension (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat. Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.

Output: Chemical/Disease Entities: angiotensin (Chemical), Captopril (Chemical), intravascular coagulation (Disease), intravascular coagulation (Disease), tranexamic acid (Chemical), AMCA (Chemical), trauma (Disease), sepsis (Disease), Captopril (Chemical), angiotensin (Chemical), Captopril (Chemical), Renal damage (Disease), urea (Chemical), Captopril (Chemical), AMCA (Chemical), Captopril (Chemical), Angiotension II (Chemical), prostacyclin (Chemical), bradykinin (Chemical), Captopril (Chemical), kidney damage (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: A randomized comparison of labetalol and nitroprusside for induced hypotension. In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.

Output: Chemical/Disease Entities: labetalol (Chemical), nitroprusside (Chemical), hypotension (Disease), labetalol (Chemical), hypotension (Disease), nitroprusside (Chemical), hypotension (Disease), reductions in mean arterial blood pressure (Disease), increase in heart rate and cardiac output (Disease), hypertension (Disease), nitroprusside (Chemical), Labetalol (Chemical), PO2 (Chemical), labetalol (Chemical), nitroprusside (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations. Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.

Output: Chemical/Disease Entities: carbamazepine (Chemical), toxicity (Disease), folate (Chemical), Folate (Chemical), Carbamazepine (Chemical), CBZ (Chemical), CBZ (Chemical), folate (Chemical), propylene glycol (Chemical), seizures (Disease), weight gain (Disease), Seizures (Disease), hexafluorodiethyl ether (Chemical), HFDE (Chemical), CBZ (Chemical), seizures (Disease), CBZ (Chemical), HFDE (Chemical), seizures (Disease), weight gain (Disease), CBZ (Chemical), CBZ (Chemical), folate (Chemical), folate (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs. In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Output: Chemical/Disease Entities: sodium (Chemical), norepinephrine (Chemical), epinephrine (Chemical), tachycardia (Disease), norepinephrine (Chemical), hypotension (Disease), hydralazine (Chemical), nitroglycerin (Chemical), epinephrine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Death from chemotherapy in gestational trophoblastic disease. Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)

Output: Chemical/Disease Entities: Death (Disease), gestational trophoblastic disease (Disease), choriocarcinoma (Disease), Etoposide (Chemical), Methotrexate (Chemical), Cyclophosphamide (Chemical), Actomycin-D (Chemical), Cisplatin (Chemical), Methotrexate (Chemical), Etoposide (Chemical), Cyclophosphamide (Chemical), pulmonary obstruction (Disease), tumor (Disease), necrosis (Disease), tumor (Disease), tumor (Disease), tumor (Disease), embolism (Disease), necrosis (Disease), pelvic tumor (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Sexual dysfunction among patients with arthritis. The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.

Output: Chemical/Disease Entities: Sexual dysfunction (Disease), arthritis (Disease), arthritis (Disease), sexual dysfunction (Disease), rheumatoid arthritis (Disease), osteoarthritis (Disease), spondyloarthropathy (Disease), depressed mood (Disease), Sexual dysfunctions (Disease), Impotence (Disease), methotrexate (Chemical), Depressed mood (Disease), impotence (Disease), arthritis (Disease), sexual dysfunction (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Does paracetamol cause urothelial cancer or renal papillary necrosis? The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.

Output: Chemical/Disease Entities: paracetamol (Chemical), urothelial cancer (Disease), renal papillary necrosis (Disease), renal papillary necrosis (Disease), phenacetin (Chemical), paracetamol (Chemical), renal papillary necrosis (Disease), phenacetin (Chemical), ureteric cancer (Disease), paracetamol (Chemical), renal papillary necrosis (Disease), cancers (Disease), cancer of the ureter (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait. A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.

Output: Chemical/Disease Entities: Dapsone (Chemical), hemolytic anemia (Disease), leprosy (Disease), hemolytic anemia (Disease), dapsone (Chemical), hemolysis (Disease), glutathione (Chemical), GSH (Chemical), GSH (Chemical), pentose phosphate (Chemical), dapsone (Chemical), dapsone (Chemical), GSH (Chemical), GSH (Chemical), pentose phosphate (Chemical), dapsone (Chemical), dapsone (Chemical), hemolytic anemia (Disease), infection (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine. A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.

Output: Chemical/Disease Entities: metoprolol (Chemical), propafenone (Chemical), diltiazem (Chemical), sparteine (Chemical), coronary artery disease (Disease), shock (Disease), AV block (Disease), hypotension (Disease), impairment of ventricular function (Disease), metoprolol (Chemical), diltiazem (Chemical), metoprolol (Chemical), diltiazem (Chemical), metoprolol (Chemical), diltiazem (Chemical), propafenone (Chemical), sparteine (Chemical), debrisoquine (Chemical), sparteine (Chemical), sparteine (Chemical), debrisoquine (Chemical), adverse drug reactions (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Triazolam-induced brief episodes of secondary mania in a depressed patient. Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.

Output: Chemical/Disease Entities: Triazolam (Chemical), mania (Disease), depressed (Disease), triazolam (Chemical), mania (Disease), depressed (Disease), organic mental disorder (Disease), delirium (Disease), Manic (Disease), triazolam (Chemical), triazolo (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats. The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.

Output: Chemical/Disease Entities: muscular rigidity (Disease), morphine (Chemical), muscular rigidity (Disease), morphine (Chemical), morphine (Chemical), rigidity (Disease), morphine (Chemical), rigidity (Disease), morphine (Chemical), akinetic (Disease), rigidity (Disease), akinetic (Disease), hyperkinetic (Disease), rigidity (Disease), haloperidol (Chemical), rigidity (Disease), Haloperidol (Chemical), rigidity (Disease), rigidity (Disease), morphine (Chemical), rigidity (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy. Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function.

Output: Chemical/Disease Entities: pentazocine (Chemical), fibrous myopathy (Disease), Fibrous myopathy (Disease), pentazocine (Chemical), compression neuropathy (Disease), pentazocine (Chemical), myopathy (Disease), pentazocine (Chemical), fibrous myopathy (Disease), fibrous myopathy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Recurrent reversible acute renal failure from amphotericin. A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.

Output: Chemical/Disease Entities: acute renal failure (Disease), amphotericin (Chemical), cirrhosis (Disease), sporotrichosis (Disease), acute renal failure (Disease), amphotericin B (Chemical), renal failure (Disease), renal dysfunction (Disease), amphotericin (Chemical), acute renal failure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy. A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.

Output: Chemical/Disease Entities: neuropathy (Disease), amiodarone (Chemical), sinuatrial disease (Disease), amiodarone (Chemical), supraventricular tachyarrhythmias (Disease), pneumonitis (Disease), proximal motor neuropathy (Disease), amiodarone (Chemical), prednisolone (Chemical), amiodarone (Chemical), pneumonitis (Disease), amiodarone (Chemical), steroid (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Indomethacin-induced renal insufficiency: recurrence on rechallenge. We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.

Output: Chemical/Disease Entities: Indomethacin (Chemical), renal insufficiency (Disease), renal failure (Disease), hyperkalemia (Disease), cirrhosis (Disease), ascites (Disease), cor pulmonale (Disease), indomethacin (Chemical), indomethacin (Chemical), oliguria (Disease), prostaglandins (Chemical), acute renal failure (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers. Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.

Output: Chemical/Disease Entities: flunitrazepam (Chemical), Flunitrazepam (Chemical), Dizziness (Disease), pain (Disease), flunitrazepam (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Changes in heart size during long-term timolol treatment after myocardial infarction. The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.

Output: Chemical/Disease Entities: timolol (Chemical), myocardial infarction (Disease), timolol (Chemical), myocardial infarction (Disease), timolol (Chemical), timolol (Chemical), timolol (Chemical), bradycardia (Disease), timolol (Chemical), cardiomegaly (Disease), infarction (Disease), timolol (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Vitamin D3 toxicity in dairy cows. Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.

Output: Chemical/Disease Entities: Vitamin D3 (Chemical), toxicity (Disease), vitamin D3 (Chemical), vitamin D3 (Chemical), hypercalcemia (Disease), hyperphosphatemia (Disease), vitamin D3 (Chemical), Calcium (Chemical), vitamin D3 (Chemical), vitamin D3 (Chemical), milk fever (Disease), milk fever (Disease), vitamin D3 (Chemical), toxicity (Disease), vitamin D3 (Chemical), toxicity (Disease), toxicity (Disease), vitamin D3 (Chemical), vitamin D3 (Chemical), milk fever (Disease), milk fever (Disease), vitamin D3 (Chemical), milk fever (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Diseases of peripheral nerves as seen in the Nigerian African. The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.

Output: Chemical/Disease Entities: Diseases of peripheral nerves (Disease), peripheral nerve disease (Disease), Sensori-motor neuropathy (Disease), Guillain-Barr   syndrome (Disease), motor neuropathy (Disease), Peripheral neuropathy (Disease), nutritional deficiency (Disease), thiamine (Chemical), riboflavin (Chemical), sensori-motor neuropathy (Disease), Diabetes mellitus (Disease), autonomic neuropathy (Disease), Isoniazid (Chemical), neuropathy (Disease), Migraine (Disease), cranial neuropathy (Disease), malignancies (Disease), neuropathy (Disease), connective tissue disorders (Disease), neuropathies (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder. In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.

Output: Chemical/Disease Entities: dothiepin hydrochloride (Chemical), depressive disorder (Disease), dothiepin (Chemical), amitriptyline (Chemical), depressed (Disease), Dothiepin (Chemical), amitriptyline (Chemical), depressive illness (Disease), blurred vision (Disease), dry mouth (Disease), dothiepin (Chemical), amitriptyline (Chemical), Dothiepin (Chemical), Dothiepin (Chemical), antidepressant (Chemical), amitriptyline (Chemical), depressed (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia. The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.

Output: Chemical/Disease Entities: diazepam (Chemical), propranolol (Chemical), panic disorder (Disease), agoraphobia (Disease), diazepam (Chemical), propranolol (Chemical), panic disorders (Disease), agoraphobia (Disease), impaired immediate free recall (Disease), diazepam (Chemical), propranolol (Chemical), Delayed free recall was also impaired (Disease), propranolol (Chemical), diazepam (Chemical), diazepam (Chemical), propranolol (Chemical), behavioral impairment (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat. The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.

Output: Chemical/Disease Entities: aspirin (Chemical), N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (Chemical), aspirin (Chemical), N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (Chemical), FANFT (Chemical), FANFT (Chemical), bladder carcinomas (Disease), forestomach tumors (Disease), FANFT (Chemical), aspirin (Chemical), aspirin (Chemical), FANFT (Chemical), FANFT (Chemical), aspirin (Chemical), aspirin (Chemical), FANFT (Chemical), FANFT (Chemical), carcinogenesis (Disease), aspirin (Chemical), FANFT (Chemical), aspirin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy? The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.

Output: Chemical/Disease Entities: hypotension (Disease), nitroglycerin (Chemical), diabetic autonomic neuropathy (Disease), nitroglycerin (Chemical), diabetic (Disease), autonomic neuropathy (Disease), diabetic (Disease), autonomic neuropathy (Disease), nitroglycerin (Chemical), diabetic (Disease), autonomic neuropathy (Disease), diabetic (Disease), autonomic neuropathy (Disease), diabetic (Disease), autonomic neuropathy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat. Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.

Output: Chemical/Disease Entities: estrogen (Chemical), adenohypophyseal tumors (Disease), Pituitary tumors (Disease), diethylstilbestrol (Chemical), DES (Chemical), DES (Chemical), DES (Chemical), acriflavine (Chemical), DES (Chemical), DES (Chemical), DES (Chemical), DES (Chemical), DES (Chemical), tumor (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Triamterene nephrolithiasis complicating dyazide therapy. A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.

Output: Chemical/Disease Entities: Triamterene (Chemical), nephrolithiasis (Disease), dyazide (Chemical), triamterene (Chemical), nephrolithiasis (Disease), hydrochlorothiazide-triamterene (Chemical), hypertension (Disease), triamterene (Chemical), uric acid salts (Chemical), triamterene (Chemical), nephrolithiasis (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Metabolic involvement in adriamycin cardiotoxicity. The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.

Output: Chemical/Disease Entities: adriamycin (Chemical), cardiotoxicity (Disease), cardiotoxic (Disease), adriamycin (Chemical), Adriamycin (Chemical), phosphorylcreatine (Chemical), adriamycin (Chemical), phophorylcreatine (Chemical), creatine (Chemical), adenosine (Chemical), ATP (Chemical), ATP (Chemical), adriamycin (Chemical), adenosine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin. Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.

Output: Chemical/Disease Entities: neurotoxic (Disease), streptomycin (Chemical), Streptomycin (Chemical), Abnormal movements (Disease), deafness (Disease), streptomycin (Chemical), dyskinesias (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis. This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.

Output: Chemical/Disease Entities: glomerulonephritis (Disease), rifampin (Chemical), pulmonary tuberculosis (Disease), glomerulonephritis (Disease), rifampin (Chemical), rifampin (Chemical), isoniazid (Chemical), pulmonary tuberculosis (Disease), renal failure (Disease), glomerulonephritis (Disease), glomerulonephritis (Disease), glomerulonephritis (Disease), glomerulonephritis (Disease), rifampin (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy. Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.

Output: Chemical/Disease Entities: puromycin aminonucleoside (Chemical), nephropathy (Disease), oxygen (Chemical), puromycin aminonucleoside (Chemical), PAN (Chemical), nephropathy (Disease), proteinuria (Disease), proteinuria (Disease), puromycin aminonucleoside (Chemical), PAN (Chemical), thiobarbituric acid (Chemical), Proteinuria (Disease), proteinuric injury (Disease), PAN (Chemical), nephropathy (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action. The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +/- 19% vs 34 +/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.

Output: Chemical/Disease Entities: Clomipramine (Chemical), sleep disturbance (Disease), sleep disturbance (Disease), clomipramine (Chemical), clomipramine (Chemical), clomipramine (Chemical), sleep disturbance (Disease), clomipramine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Angioedema following the intravenous administration of metoprolol. A 72-year-old woman was admitted to the hospital with "flash" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.

Output: Chemical/Disease Entities: Angioedema (Disease), metoprolol (Chemical), pulmonary edema (Disease), chest pain (Disease), coronary artery disease (Disease), myocardial infarctions (Disease), hypertension (Disease), diabetes mellitus (Disease), angioedema (Disease), lisinopril (Chemical), angiotensin (Chemical), metoprolol (Chemical), angioedema (Disease), angioedema (Disease), steroids (Chemical), diphenhydramine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effect of coniine on the developing chick embryo. Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.

Output: Chemical/Disease Entities: coniine (Chemical), Coniine (Chemical), arthrogryposis (Disease), coniine (Chemical), arthrogryposis (Disease), coniine (Chemical), nicotine (Chemical), coniine (Chemical), nicotine (Chemical), deformations (Disease), nicotine (Chemical), coniine (Chemical), deformations (Disease), coniine (Chemical), nicotine (Chemical), excessive flexion or extension of one or more toes (Disease), cranial hemorrhage (Disease), nicotine (Chemical), coniine (Chemical), nicotine (Chemical), coniine (Chemical), nicotine (Chemical), coniine (Chemical), arthrogryposis (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension. To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.

Output: Chemical/Disease Entities: prostaglandin E1 (Chemical), trimethaphan (Chemical), hypotension (Disease), prostaglandin E1 (Chemical), PGE1 (Chemical), trimethaphan (Chemical), TMP (Chemical), hypotension (Disease), isoflurane (Chemical), PGE1 (Chemical), TMP (Chemical), hypotensive (Disease), PGE1 (Chemical), TMP (Chemical), hypotension (Disease), PGE1 (Chemical), PGE1 (Chemical), TMP (Chemical), TMP (Chemical), PGE1 (Chemical), TMP (Chemical), hypotensive (Disease), TMP (Chemical)


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Input: Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat. Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.

Output: Chemical/Disease Entities: axonal damage (Disease), axonal injury (Disease), injury in the cortex (Disease), lactate (Chemical), Infarcts in substantia nigra pars reticulata (Disease), pilocarpine (Chemical), status epilepticus (Disease), axonal damage (Disease), traumatic (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Increase of Parkinson disability after fluoxetine medication. Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.

Output: Chemical/Disease Entities: Parkinson disability (Disease), fluoxetine (Chemical), Depression (Disease), Parkinson's disease (Disease), motor disability (Disease), idiopathic Parkinson's disease (Disease), antidepressant (Chemical), fluoxetine (Chemical), dopamine (Chemical), fluoxetine (Chemical), Parkinson's disease (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Acetaminophen-induced hypotension. Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.

Output: Chemical/Disease Entities: Acetaminophen (Chemical), hypotension (Disease), acetaminophen (Chemical), acetaminophen (Chemical), cardiovascular toxicities (Disease), acetaminophen (Chemical), anaphylaxis (Disease), hypotension (Disease), critically ill (Disease), hypotension (Disease), acetaminophen (Chemical), allergic reactions (Disease), hypotensive (Disease), acetaminophen (Chemical), hypotension (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone. An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.

Output: Chemical/Disease Entities: hepatitis (Disease), autoimmune hemolytic anemia (Disease), erythroblastocytopenia (Disease), ceftriaxone (Chemical), hepatitis (Disease), ceftriaxone (Chemical), beta lactam (Chemical), bilirubin (Chemical), autoimmune hemolytic anemia (Disease), erythroblastocytopenia (Disease), steroids (Chemical), beta lactam (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations. Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Output: Chemical/Disease Entities: extrapyramidal symptoms (Disease), EPS (Disease), tardive dyskinesia (Disease), orthostatic hypotension (Disease), sexual dysfunction (Disease), weight gain (Disease), EPS (Disease), weight gain (Disease), sexual dysfunction (Disease), seizure (Disease), clozapine (Chemical), agranulocytosis (Disease), clozapine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation. Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.

Output: Chemical/Disease Entities: tetrandrine (Chemical), fangchinoline (Chemical), thrombosis (Disease), platelet aggregation (Disease), Tetrandrine (Chemical), TET (Chemical), fangchinoline (Chemical), FAN (Chemical), bisbenzylisoquinoline (Chemical), TET (Chemical), FAN (Chemical), thrombosis (Disease), epinephrine (Chemical), EP (Chemical), platelet aggregation (Disease), blood coagulation (Disease), TET (Chemical), FAN (Chemical), thrombosis (Disease), acetylsalicylic acid (Chemical), ASA (Chemical), platelet aggregations (Disease), TET (Chemical), FAN (Chemical), TET (Chemical), FAN (Chemical), TET (Chemical), FAN (Chemical)


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Input: Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group. BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.

Output: Chemical/Disease Entities: Gemcitabine (Chemical), vinorelbine (Chemical), nonsmall cell lung carcinoma (Disease), cisplatin (Chemical), nonsmall cell lung carcinoma (Disease), NSCLC (Disease), toxicity (Disease), vinorelbine (Chemical), VNB (Chemical), gemcitabine (Chemical), GEM (Chemical), toxicity (Disease), toxicity (Disease), GEM (Chemical), VNB (Chemical), NSCLC (Disease), cisplatin (Chemical), NSCLC (Disease), cisplatin (Chemical), toxicity (Disease), VNB (Chemical), GEM (Chemical), Toxicity (Disease), neutropenia (Disease), thrombocytopenia (Disease), neurotoxicity (Disease), neutropenia (Disease), sepsis (Disease), neutropenia (Disease), GEM (Chemical), VNB (Chemical), myelosuppression (Disease), toxicity (Disease), NSCLC (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Warfarin-induced artery calcification is accelerated by growth and vitamin D. The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.

Output: Chemical/Disease Entities: Warfarin (Chemical), artery calcification (Disease), vitamin D (Chemical), vitamin D (Chemical), artery calcification (Disease), Warfarin (Chemical), calcification (Disease), artery calcification (Disease), Warfarin (Chemical), Warfarin (Chemical), calcification of the artery (Disease), calcification (Disease), artery calcification (Disease), Warfarin (Chemical), Warfarin (Chemical), artery calcification (Disease), Warfarin (Chemical), calcification of the artery (Disease), artery calcification (Disease), artery calcification (Disease), phosphate (Chemical), artery calcification (Disease), phosphate (Chemical), Warfarin (Chemical), artery calcification (Disease), Warfarin (Chemical), artery calcification (Disease), phosphate (Chemical), vitamin D (Chemical), Warfarin (Chemical), artery calcification (Disease), vitamin D (Chemical), calcification of the artery (Disease), vitamin K (Chemical), Warfarin (Chemical), calcification of the artery (Disease), Warfarin (Chemical), calcification (Disease), vitamin D (Chemical), vitamin D (Chemical), artery calcification (Disease), vitamin D (Chemical), calcium (Chemical), vitamin D (Chemical), artery calcification (Disease), calcium (Chemical), Warfarin (Chemical), calcium (Chemical), vitamin D (Chemical), Warfarin (Chemical), vitamin D (Chemical), Warfarin (Chemical), calcification (Disease), artery calcification (Disease), vitamin D (Chemical), Warfarin (Chemical), gamma-carboxylated (Chemical), gamma-carboxyglutamate (Chemical), calcification (Disease), calcification (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Antidepressant-induced mania in bipolar patients: identification of risk factors. BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.

Output: Chemical/Disease Entities: Antidepressant (Chemical), mania (Disease), bipolar (Disease), mania (Disease), antidepressants (Chemical), bipolar depression (Disease), bipolar disorder (Disease), manic (Disease), hypomanic (Disease), DSM-IV bipolar I (Disease), bipolar II (Disease), manic (Disease), antidepressant (Chemical), antidepressant (Chemical), serotonin reuptake inhibitors (Chemical), SSRIs (Chemical), lithium (Chemical), hypomania (Disease), mania (Disease), SSRIs (Chemical), manic (Disease), hypomanic (Disease), bipolar I (Disease), bipolar II (Disease), lithium (Chemical), lithium (Chemical), manic (Disease), antidepressant (Chemical), lithium (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a "natural energy" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.

Output: Chemical/Disease Entities: Caffeine (Chemical), cardiac arrhythmia (Disease), mitral valve prolapse (Disease), ventricular fibrillation (Disease), caffeine (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports. Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.

Output: Chemical/Disease Entities: retention of urine (Disease), fentanyl (Chemical), pain (Disease), Fentanyl (Chemical), fentanyl (Chemical), chest wall rigidity (Disease), hypotension (Disease), respiratory depression (Disease), bradycardia (Disease), urinary bladder retention (Disease), hydronephrosis (Disease), fentanyl (Chemical)


Instruction: Extract chemical and disease entities from the following text.

Input: Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice. Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.

Output: Chemical/Disease Entities: cardiomyopathy (Disease), lactate (Chemical), AIDS (Disease), cardiomyopathy (Disease), CM (Disease), lactate (Chemical), LA (Chemical), AIDS (Disease), mitochondrial dysfunction (Disease), AIDS (Disease), zidovudine (Chemical), lamivudine (Chemical), indinavir (Chemical), CM (Disease), calcium (Chemical), LA (Chemical), LA (Chemical), CM (Disease), LA (Chemical), AIDS (Disease)


Instruction: Extract chemical and disease entities from the following text.

Input: Oral contraceptives and the risk of myocardial infarction. BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.

Output: Chemical/Disease Entities: Oral contraceptives (Chemical), myocardial infarction (Disease), oral contraceptives (Chemical), myocardial infarction (Disease), progestagen (Chemical), desogestrel (Chemical), gestodene (Chemical), levonorgestrel (Chemical), oral contraceptives (Chemical), estrogen (Chemical), myocardial infarction (Disease), myocardial infarction (Disease), oral-contraceptive (Chemical), myocardial infarction (Disease), oral contraceptive (Chemical), oral contraceptives (Chemical), oral contraceptives (Chemical), oral contraceptives (Chemical), myocardial infarction (Disease), oral contraceptives (Chemical), oral contraceptives (Chemical), oral contraceptives (Chemical), myocardial infarction (Disease), oral contraceptives (Chemical)