Input: Case report: acute unintentional carbachol intoxication. INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84 - year - old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer' s disease. The mode of action was said to be comparable to that of the synthetic compound' carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC - mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100 / 65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio - ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3. 6 and 1. 9 mg / l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg / l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer - reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.

carbachol

carbachol

carbamylcholin

carbachol

carbachol

Carbachol

adrenaline

epinephrine

atropine

furosemide

atropine

adrenaline

dopamine

carbachol

carbachol

carbachol

poisoning

Alzheimer' s disease

nausea

hypotension

Bradycardia

asystole

hyperhidrosis

hypersalivation

bronchorrhoea

miosis

atrio - ventricular dissociation

dyspnoea

bronchospasm

Respiratory insufficiency

Proteus mirabilis infection

heart failure

acute cardiovascular failure

carbachol

nausea

carbachol

nausea

carbamylcholin

nausea

carbachol

nausea

carbachol

nausea

Carbachol

nausea

carbachol

nausea

carbachol

nausea

carbachol

nausea

carbachol

Bradycardia

carbachol

Bradycardia

carbamylcholin

Bradycardia

carbachol

Bradycardia

carbachol

Bradycardia

Carbachol

Bradycardia

carbachol

Bradycardia

carbachol

Bradycardia

carbachol

Bradycardia

carbachol

asystole

carbachol

asystole

carbamylcholin

asystole

carbachol

asystole

carbachol

asystole

Carbachol

asystole

carbachol

asystole

carbachol

asystole

carbachol

asystole

carbachol

heart failure

carbachol

heart failure

carbamylcholin

heart failure

carbachol

heart failure

carbachol

heart failure

Carbachol

heart failure

carbachol

heart failure

carbachol

heart failure

carbachol

heart failure

carbachol

hypotension

carbachol

hypotension

carbamylcholin

hypotension

carbachol

hypotension

carbachol

hypotension

Carbachol

hypotension

carbachol

hypotension

carbachol

hypotension

carbachol

hypotension

carbachol

miosis

carbachol

miosis

carbamylcholin

miosis

carbachol

miosis

carbachol

miosis

Carbachol

miosis

carbachol

miosis

carbachol

miosis

carbachol

miosis

carbachol

hyperhidrosis

carbachol

hyperhidrosis

carbamylcholin

hyperhidrosis

carbachol

hyperhidrosis

carbachol

hyperhidrosis

Carbachol

hyperhidrosis

carbachol

hyperhidrosis

carbachol

hyperhidrosis

carbachol

hyperhidrosis

carbachol

hypersalivation

carbachol

hypersalivation

carbamylcholin

hypersalivation

carbachol

hypersalivation

carbachol

hypersalivation

Carbachol

hypersalivation

carbachol

hypersalivation

carbachol

hypersalivation

carbachol

hypersalivation


Input: Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine / caffeine in migraine. Rizatriptan is a selective 5 - HT (1B / 1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double - blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg / caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89. 1%), more than twice as many preferred rizatriptan to ergotamine / caffeine (69. 9 vs. 30. 1%, p < or = 0. 001). Faster relief of headache was the most important reason for preference, cited by 67. 3% of patients preferring rizatriptan and 54. 2% of patients who preferred ergotamine / caffeine. The co - primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty - nine percent of patients were pain free 2 h after rizatriptan, compared with 24. 3% treated with ergotamine / caffeine (p < or = 0. 001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75. 9% for rizatriptan and 47. 3% for ergotamine / caffeine (p < or = 0. 001), with rizatriptan being superior to ergotamine / caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine / caffeine (p < or = 0. 001). Rizatriptan was also superior to ergotamine / caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0. 001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69. 8%) than at 2 h after treatment with ergotamine / caffeine (38. 6%, p < or = 0. 001). Recurrence rates were 31. 4% with rizatriptan and 15. 3% with ergotamine / caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine / caffeine, respectively, were dizziness (6. 7 and 5. 3%), nausea (4. 2 and 8. 5%) and somnolence (5. 5 and 2. 3%).

rizatriptan

ergotamine

caffeine

Rizatriptan

5 - HT

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

rizatriptan

rizatriptan

ergotamine

caffeine

rizatriptan

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

Rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

rizatriptan

ergotamine

caffeine

migraine

migraine

migraine

headache

pain

pain

Headache

pain

nausea

vomiting

phonophobia

photophobia

dizziness

nausea

somnolence

rizatriptan

nausea

rizatriptan

nausea

Rizatriptan

nausea

Rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

Rizatriptan

nausea

Rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

nausea

rizatriptan

dizziness

Rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

Rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness

rizatriptan

dizziness


Input: Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic - uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor - free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug - induced bone marrow suppression.

Thrombotic microangiopathy

renal failure

carcinoma

thrombotic microangiopathy

renal insufficiency

microangiopathic hemolytic anemia

thrombocytopenia

thrombotic thrombocytopenic purpura

hemolytic - uremic syndrome

intravascular coagulation

tumor

tumor

thrombotic microangiopathy

renal failure

nephrotoxicity

anemia

thrombocytopenia

bone marrow suppression

cisplatin

bleomycin

vinca alkaloid

cisplatin

bleomycin

thrombotic thrombocytopenic purpura

vinca alkaloid

hemolytic - uremic syndrome

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

vinca alkaloid

nephrotoxicity

cisplatin

thrombotic thrombocytopenic purpura

cisplatin

thrombotic thrombocytopenic purpura

bleomycin

hemolytic - uremic syndrome

vinca alkaloid

thrombotic thrombocytopenic purpura

cisplatin

hemolytic - uremic syndrome

cisplatin

hemolytic - uremic syndrome

bleomycin

nephrotoxicity


Input: Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed / refractory paediatric T - cell lymphoblastic leukaemia and lymphoma. A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T - cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG / VP / CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.

nelarabine

etoposide

cyclophosphamide

nelarabine

AraG

etoposide

VP

cyclophosphamide

CPM

AraG

AraG

AraG

VP

CPM

AraG

etoposide

cyclophosphamide

T - cell lymphoblastic leukaemia and lymphoma

T - cell lymphoblastic leukaemia

T - cell lymphoblastic leukaemia and lymphoma

T - cell leukaemia or lymphoma

T - cell leukaemia

T - cell leukaemia or lymphoma

neuropathy

musculoskeletal pain

Haematological toxicity

neurological toxicity

nelarabine

neuropathy

nelarabine

neurological toxicity

nelarabine

neuropathy

nelarabine

neurological toxicity

AraG

neuropathy

AraG

neurological toxicity

AraG

neuropathy

AraG

neurological toxicity

AraG

neuropathy

AraG

neurological toxicity

AraG

neuropathy

AraG

neurological toxicity

AraG

neuropathy

AraG

neurological toxicity

nelarabine

Haematological toxicity

nelarabine

Haematological toxicity

AraG

Haematological toxicity

AraG

Haematological toxicity

AraG

Haematological toxicity

AraG

Haematological toxicity

AraG

Haematological toxicity

nelarabine

musculoskeletal pain

nelarabine

musculoskeletal pain

AraG

musculoskeletal pain

AraG

musculoskeletal pain

AraG

musculoskeletal pain

AraG

musculoskeletal pain

AraG

musculoskeletal pain


Input: The 3 - week sulphasalazine syndrome strikes again. A 34 - year - old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero - negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction. A week later, fulminant drug - induced hepatitis, associated with the presence of anti - nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi - organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy. Post - mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo - interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico - pathological features and chronology of this case bore the hallmarks of the so - called " 3 - week sulphasalazine syndrome ", a rare, but often fatal, immunoallergic reaction to sulphasalazine.

sulphasalazine

sulphasalazine

sulphasalazine

sulphasalazine

dermatitis

fever

lymphadenopathy

hepatitis

rheumatoid arthritis

lymphadenitis

adverse drug reaction

drug - induced hepatitis

autoimmunity

multi - organ failure

sepsis

massive hepatocellular necrosis

myocarditis

nephritis

bone marrow necrosis

malignancy

sulphasalazine

fever

sulphasalazine

fever

sulphasalazine

fever

sulphasalazine

fever

sulphasalazine

myocarditis

sulphasalazine

myocarditis

sulphasalazine

myocarditis

sulphasalazine

myocarditis

sulphasalazine

lymphadenopathy

sulphasalazine

lymphadenopathy

sulphasalazine

lymphadenopathy

sulphasalazine

lymphadenopathy

sulphasalazine

sepsis

sulphasalazine

sepsis

sulphasalazine

sepsis

sulphasalazine

sepsis

sulphasalazine

nephritis

sulphasalazine

nephritis

sulphasalazine

nephritis

sulphasalazine

nephritis

sulphasalazine

dermatitis

sulphasalazine

dermatitis

sulphasalazine

dermatitis

sulphasalazine

dermatitis

sulphasalazine

hepatitis

sulphasalazine

drug - induced hepatitis

sulphasalazine

hepatitis

sulphasalazine

drug - induced hepatitis

sulphasalazine

hepatitis

sulphasalazine

drug - induced hepatitis

sulphasalazine

hepatitis

sulphasalazine

drug - induced hepatitis


Input: Bupropion (Zyban) toxicity. Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained - release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it' s introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13. 5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.

Bupropion

Zyban

Bupropion

antidepressant

amphetamine

Zyban

bupropion hydrochloride

bupropion

diazepam

adenosine

Zyban

toxicity

overdose

toxicity

tachycardia

hallucinations

convulsions

cardiac arrhythmias

cardiac arrest

seizures

tachycardia

neurological and cardiovascular toxicity

neurological and cardiovascular toxicity

cardiovascular toxicity

overdose

Bupropion

tachycardia

Bupropion

tachycardia

Zyban

tachycardia

Zyban

tachycardia

Bupropion

tachycardia

Bupropion

tachycardia

Zyban

tachycardia

Zyban

tachycardia

bupropion hydrochloride

tachycardia

bupropion hydrochloride

tachycardia

bupropion

tachycardia

bupropion

tachycardia

Zyban

tachycardia

Zyban

tachycardia

Bupropion

convulsions

Bupropion

seizures

Zyban

convulsions

Zyban

seizures

Bupropion

convulsions

Bupropion

seizures

Zyban

convulsions

Zyban

seizures

bupropion hydrochloride

convulsions

bupropion hydrochloride

seizures

bupropion

convulsions

bupropion

seizures

Zyban

convulsions

Zyban

seizures

Bupropion

hallucinations

Zyban

hallucinations

Bupropion

hallucinations

Zyban

hallucinations

bupropion hydrochloride

hallucinations

bupropion

hallucinations

Zyban

hallucinations

Bupropion

cardiac arrhythmias

Zyban

cardiac arrhythmias

Bupropion

cardiac arrhythmias

Zyban

cardiac arrhythmias

bupropion hydrochloride

cardiac arrhythmias

bupropion

cardiac arrhythmias

Zyban

cardiac arrhythmias

Bupropion

cardiac arrest

Zyban

cardiac arrest

Bupropion

cardiac arrest

Zyban

cardiac arrest

bupropion hydrochloride

cardiac arrest

bupropion

cardiac arrest

Zyban

cardiac arrest


Input: Survey of complications of indocyanine green angiography in Japan. PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3, 774 indocyanine green angiograms performed on 2, 820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0. 34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.

indocyanine green

indocyanine green

indocyanine green

indocyanine green

indocyanine green

indocyanine green

indocyanine green

indocyanine green

fluorescein sodium

indocyanine green

fluorescein

nausea

exanthema

urtication

itchiness

pain

hypotension

hypotensive

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

shock

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

pain

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

hypotension

indocyanine green

hypotensive

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

itchiness

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

nausea

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

exanthema

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication

indocyanine green

urtication


Input: Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model. PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L - NOArg; 1. 0 mg / kg ip), a relatively selective inhibitor of inducible NO synthase (L - NIL; 1. 0 mg / kg ip) and a relatively specific inhibitor of neuronal NO synthase (7 - NI; 0. 1 mg / kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D - Arg - [Hyp3, Thi5, D - Tic7, Oic8] bradykinin (HOE 140; 70 nmol / kg ip) or des Arg10 HOE 140 (70 nmol / kg ip) respectively, in model of diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli - - the modification of the classic paw withdrawal test described by Randall - Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L - NOArg and L - NIL but not 7 - NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L - NOArg and 7 - NI but not L - NIL intensify antihyperalgesic activity of HOE 140 or des - Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin - induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine - induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.

Bradykinin

nitric oxide

vincristine

streptozotocin

NO

NO

NO

bradykinin

HOE 140

des Arg10 HOE 140

bradykinin

NO

NO

HOE 140

des Arg10 HOE 140

NO

NO

bradykinin

vincristine

HOE 140

des - Arg10HOE 140

streptozotocin

NO

bradykinin

vincristine

bradykinin

NO

bradykinin

NO

hyperalgesia

diabetic neuropathy

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

toxic (vincristine - induced) neuropathy

pain

diabetic hyperalgesia

hyperalgesia

toxic neuropathy

diabetic and toxic neuropathy

diabetic and toxic neuropathy

toxic neuropathy

hyperalgesia

hyperalgesia

neuropathic pain

streptozotocin

diabetic neuropathy

streptozotocin

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

streptozotocin

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

streptozotocin

diabetic and toxic neuropathy

streptozotocin

diabetic and toxic neuropathy

streptozotocin

diabetic neuropathy

streptozotocin

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

streptozotocin

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

streptozotocin

diabetic and toxic neuropathy

streptozotocin

diabetic and toxic neuropathy

streptozotocin

hyperalgesia

streptozotocin

diabetic hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

diabetic hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

hyperalgesia

streptozotocin

hyperalgesia

vincristine

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

vincristine

toxic (vincristine - induced) neuropathy

vincristine

toxic neuropathy

vincristine

diabetic and toxic neuropathy

vincristine

toxic neuropathy

vincristine

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

vincristine

toxic (vincristine - induced) neuropathy

vincristine

toxic neuropathy

vincristine

diabetic and toxic neuropathy

vincristine

toxic neuropathy

vincristine

diabetic (streptozotocin - induced) and toxic (vincristine - induced) neuropathy

vincristine

toxic (vincristine - induced) neuropathy

vincristine

toxic neuropathy

vincristine

diabetic and toxic neuropathy

vincristine

toxic neuropathy

vincristine

hyperalgesia

vincristine

diabetic hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

diabetic hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

diabetic hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia

vincristine

hyperalgesia


Input: Cardiac toxicity observed in association with high - dose cyclophosphamide - based chemotherapy for metastatic breast cancer. INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose - limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high - dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high - dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy - responsive metastatic breast cancer receiving 96 - h infusional cyclophosphamide as part of a triple sequential high - dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left - sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide - related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.

Cardiac toxicity

breast cancer

toxicity

cardiomyopathy

breast cancer

breast cancer

congestive heart failure

CHF

hypertension

diabetes mellitus

CHF

cardiac toxicity

CHF

CHF

CHF

cyclophosphamide

Cyclophosphamide

paclitaxel

melphalan

cyclophosphamide

thiotepa

carboplatin

cyclophosphamide

anthracyclines

cyclophosphamide

cyclophosphamide

cyclophosphamide

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

Cyclophosphamide

congestive heart failure

Cyclophosphamide

CHF

Cyclophosphamide

CHF

Cyclophosphamide

CHF

Cyclophosphamide

CHF

Cyclophosphamide

CHF

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

congestive heart failure

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF

cyclophosphamide

CHF


Input: Inappropriate use of carbamazepine and vigabatrin in typical absence seizures. Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add - on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.

carbamazepine

vigabatrin

Carbamazepine

vigabatrin

carbamazepine

Vigabatrin

carbamazepine

carbamazepine

vigabatrin

sodium valproate

lamotrigine

ethosuximide

absence seizures

absence seizures

myoclonic jerks

carbamazepine

absence seizures

carbamazepine

absence seizures

Carbamazepine

absence seizures

Carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

absence seizures

carbamazepine

myoclonic jerks

Carbamazepine

myoclonic jerks

carbamazepine

myoclonic jerks

carbamazepine

myoclonic jerks

carbamazepine

myoclonic jerks

vigabatrin

absence seizures

vigabatrin

absence seizures

vigabatrin

absence seizures

vigabatrin

absence seizures

Vigabatrin

absence seizures

Vigabatrin

absence seizures

vigabatrin

absence seizures

vigabatrin

absence seizures


Input: Hemolytic anemia associated with the use of omeprazole. Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger - Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short - term safety of this drug. We report the first case of a serious short - term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44. 1% to 20. 4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient' s hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.

Hemolytic anemia

peptic ulcer disease

reflux esophagitis

Zollinger - Ellison syndrome

hemolytic anemia

lethargy

shortness of breath

hemolytic anemia

omeprazole

Omeprazole

omeprazole

omeprazole

omeprazole

bilirubin

omeprazole

omeprazole

omeprazole

shortness of breath

Omeprazole

shortness of breath

omeprazole

shortness of breath

omeprazole

shortness of breath

omeprazole

shortness of breath

omeprazole

shortness of breath

omeprazole

shortness of breath

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

Omeprazole

Hemolytic anemia

Omeprazole

hemolytic anemia

Omeprazole

hemolytic anemia

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

Hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

hemolytic anemia

omeprazole

lethargy

Omeprazole

lethargy

omeprazole

lethargy

omeprazole

lethargy

omeprazole

lethargy

omeprazole

lethargy

omeprazole

lethargy


Input: The use and toxicity of didanosine (ddI) in HIV antibody - positive individuals intolerant to zidovudine (AZT) One hundred and fifty - one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12. 5 mg / kg / day. Patient response was assessed using changes in CD4 + lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4 + lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4 + lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side - effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.

toxicity

HIV antibody - positive

opportunistic infections

AIDS

AIDS

diarrhoea

Peripheral neuropathy

pancreatitis

abdominal pain

glucose tolerance curves

diabetes

didanosine

ddI

zidovudine

AZT

zidovudine

AZT

didanosine

ddI

didanosine

didanosine

didanosine

glucose tolerance curves

ddI

glucose tolerance curves

didanosine

glucose tolerance curves

ddI

glucose tolerance curves

didanosine

glucose tolerance curves

didanosine

glucose tolerance curves

didanosine

Peripheral neuropathy

ddI

Peripheral neuropathy

didanosine

Peripheral neuropathy

ddI

Peripheral neuropathy

didanosine

Peripheral neuropathy

didanosine

Peripheral neuropathy

didanosine

diarrhoea

ddI

diarrhoea

didanosine

diarrhoea

ddI

diarrhoea

didanosine

diarrhoea

didanosine

diarrhoea

didanosine

pancreatitis

ddI

pancreatitis

didanosine

pancreatitis

ddI

pancreatitis

didanosine

pancreatitis

didanosine

pancreatitis


Input: Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia? BACKGROUND / AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin - 2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.

ribavirin

ribavirin

sunitinib

sorafenib

pegylated interferon alpha 2a

ribavirin

pegylated interferon

ribavirin

ribavirin

ribavirin

hemolytic anemia

hemolysis

anemia

chronically infected with hepatitis C virus

anemia

hepatitis C

sorafenib

hemolysis

sunitinib

hemolysis


Input: Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate. Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced - behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.

Cocaine

topiramate

cocaine

cocaine

nitric oxide

topiramate

cocaine

cocaine

GSH

glutathione

cocaine

glutathione

cocaine

Topiramate

memory and learning impairments

memory and learning impairments

learning impairments

toxicity

toxicity

cocaine addiction

Cocaine

memory and learning impairments

Cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

cocaine

memory and learning impairments

cocaine

learning impairments

Cocaine

memory and learning impairments

cocaine

memory and learning impairments

cocaine

memory and learning impairments

cocaine

memory and learning impairments

cocaine

memory and learning impairments

cocaine

memory and learning impairments

cocaine

memory and learning impairments


Input: Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG - 9. The antinociceptive effect of 3 alpha - tropyl 2 - (p - bromophenyl) propionate [(+ / -) - PG - 9] (10 - 40 mg kg - 1 s. c.; 30 - 60 mg kg - 1 p. o.; 10 - 30 mg kg - 1 i. v.; 10 - 30 micrograms / mouse i. c. v.) was examined in mice, rats and guinea pigs by use of the hot - plate, abdominal - constriction, tail - flick and paw - pressure tests. (+ / -) - PG - 9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+ / -) - PG - 9 was prevented by the unselective muscarinic antagonist atropine, the M1 - selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium - 3, but not by the opioid antagonist naloxone, the gamma - aminobutyric acidB antagonist 3 - aminopropyl - diethoxy - methyl - phosphinic acid, the H3 agonist R - (alpha) - methylhistamine, the D2 antagonist quinpirole, the 5 - hydroxytryptamine4 antagonist 2 - methoxy - 4 - amino - 5 - chlorobenzoic acid 2 - (diethylamino) ethyl ester hydrochloride, the 5 - hydroxytryptamin1A antagonist 1 - (2 - methoxyphenyl) - 4 - [4 - (2 - phthalimido) butyl] piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+ / -) - PG - 9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+ / -) - PG - 9 (10 - 40 mg kg - 1 i. p.) was able to prevent amnesia induced by scopolamine (1 mg kg - 1 i. p.) and dicyclomine (2 mg kg - 1 i. p.) in the mouse passive - avoidance test. Affinity profiles of (+ / -) - PG - 9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4 / M1 selectivity ratio of 10. 2 that might be responsible for the antinociception and the anti - amnesic effect induced by (+ / -) - PG - 9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+ / -) - PG - 9 did not impair mouse performance evaluated by the rota - rod test and Animex apparatus.

PG - 9

3 alpha - tropyl 2 - (p - bromophenyl) propionate

PG - 9

PG - 9

PG - 9

atropine

pirenzepine

dicyclomine

acetylcholine

hemicholinium - 3

naloxone

gamma - aminobutyric acidB

3 - aminopropyl - diethoxy - methyl - phosphinic acid

R - (alpha) - methylhistamine

quinpirole

5 - hydroxytryptamine4

2 - methoxy - 4 - amino - 5 - chlorobenzoic acid 2 - (diethylamino) ethyl ester

5 - hydroxytryptamin1A

1 - (2 - methoxyphenyl) - 4 - [4 - (2 - phthalimido) butyl] piperazine

reserpine

PG - 9

PG - 9

scopolamine

dicyclomine

PG - 9

PG - 9

acetylcholine

PG - 9

amnesia

amnesic

scopolamine

amnesia

scopolamine

amnesic

dicyclomine

amnesia

dicyclomine

amnesic

dicyclomine

amnesia

dicyclomine

amnesic


Input: Hyperbaric oxygen therapy for control of intractable cyclophosphamide - induced hemorrhagic cystitis. We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener' s granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide - induced hemorrhagic cystitis.

oxygen

cyclophosphamide

cyclophosphamide

prostaglandin F2 alpha

oxygen

cyclophosphamide

hemorrhagic cystitis

hemorrhagic

cystitis

hemorrhagic cystitis

hemorrhagic

cystitis

Wegener' s granulomatosis

hemorrhage

bleeding

hematuria

hemorrhagic cystitis

hemorrhagic

cystitis

cyclophosphamide

hematuria

cyclophosphamide

hematuria

cyclophosphamide

hematuria

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic cystitis

cyclophosphamide

cystitis

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhage

cyclophosphamide

bleeding

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhage

cyclophosphamide

bleeding

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhagic

cyclophosphamide

hemorrhage

cyclophosphamide

bleeding

cyclophosphamide

hemorrhagic


Input: Further studies on effects of irrigation solutions on rat bladders. Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p - choloroaniline is not a significant factor in chlorhexidine - digluconate associated erosive cystitis. A high percentage of kanamycin - colistin and povidone - iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.

p - choloroaniline

chlorhexidine - digluconate

kanamycin

colistin

povidone - iodine

Picloxydine

cystitis

cystitis

cystitis

chlorhexidine - digluconate

cystitis

chlorhexidine - digluconate

cystitis

chlorhexidine - digluconate

cystitis

colistin

cystitis

colistin

cystitis

colistin

cystitis

kanamycin

cystitis

kanamycin

cystitis

kanamycin

cystitis

povidone - iodine

cystitis

povidone - iodine

cystitis

povidone - iodine

cystitis


Input: Clinical experiences in an open and a double - blind trial. A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4. 47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.

bromperidol

haloperidol

haloperidol

bromperidol

extrapyramidal concomitant symptoms

psychotic syndromes belonging predominantly to the schizophrenia group

haloperidol

extrapyramidal concomitant symptoms

haloperidol

extrapyramidal concomitant symptoms

bromperidol

extrapyramidal concomitant symptoms

bromperidol

extrapyramidal concomitant symptoms


Input: Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats. The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti - inflammatory and neuro - protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone - and carbamazepine - induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle / drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co - administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.

Curcumin

phenobarbitone

carbamazepine

phenobarbitone

carbamazepine

Curcumin

curcumin

phenobarbitone

carbamazepine

curcumin

phenobarbitone

carbamazepine

phenobarbitone

carbamazepine

malondialdehyde

glutathione

phenobarbitone

carbamazepine

curcumin

Curcumin

phenobarbitone

carbamazepine

curcumin

phenobarbitone

carbamazepine

curcumin

phenobarbitone

carbamazepine

cognitive dysfunction

cognitive impairment

cognitive impairment

cognitive impairment

impairment of learning and memory

cognitive impairment

deterioration of cognitive functions

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

phenobarbitone

cognitive dysfunction

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

cognitive impairment

phenobarbitone

impairment of learning and memory

phenobarbitone

cognitive impairment

phenobarbitone

deterioration of cognitive functions

phenobarbitone

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment

carbamazepine

cognitive dysfunction

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

cognitive impairment

carbamazepine

impairment of learning and memory

carbamazepine

cognitive impairment

carbamazepine

deterioration of cognitive functions

carbamazepine

cognitive impairment


Input: Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model. Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa - beta. Both, production of reactive oxygen species as well as activation of NF - kappaB have been implicated in severe neuronal damage in different sub - regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus - associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg / kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg / kg PDTC (low - dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle - treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low - dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle - and PDTC - treated rats following status epilepticus. In conclusion, the NF - kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF - kappaB plays a more central role in seizure - associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.

Pyrrolidine dithiocarbamate

pilocarpine

Pyrrolidine dithiocarbamate

PDTC

oxygen

PDTC

pilocarpine

PDTC

PDTC

PDTC

PDTC

PDTC

oxygen

PDTC

status epilepticus

neuronal damage

status epilepticus

status epilepticus

status epilepticus

status epilepticus

neuronal damage

status epilepticus

neuronal loss

seizure

neuronal damage

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

neuronal damage

pilocarpine

neuronal damage

pilocarpine

neuronal loss

pilocarpine

neuronal damage

pilocarpine

neuronal damage

pilocarpine

neuronal damage

pilocarpine

neuronal loss

pilocarpine

neuronal damage


Input: Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12 - week, randomized, open - label study. BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4 - mg nicotine lozenge and 4 - mg nicotine gum in smokers with selected label - restricted diseases. METHODS: This was a multicenter, randomized, open - label study in adult smokers with heart disease, hypertension not controlled by medication, and / or diabetes mellitus. Patients were randomized in a 1: 1 ratio to receive the 4 - mg nicotine lozenge or 4 - mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52. 7%). Patients' mean age was 53. 9 years, their mean weight was 193. 9 pounds, and they smoked a mean of 25. 2 cigarettes per day at baseline. Five hundred fifty - three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or = 4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55. 3% lozenge, 54. 7% gum), as well as during the entire study (safety population: 63. 8% and 58. 6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17. 2% and 16. 1%; 95% CI, - 3. 7 to 6. 0), hiccups (10. 7% and 6. 6%; 95% CI, 0. 5 to 7. 8), and headache (8. 7% and 9. 9%; 95% Cl, - 5. 0 to 2. 6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (> 60%) experienced no change in their disease status from baseline. CONCLUSION: The 4 - mg nicotine lozenge and 4 - mg nicotine gum had comparable safety profiles in these patients with label - restricted medical conditions.

nicotine

nicotine

Nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

nicotine

heart disease

hypertension

diabetes mellitus

nausea

hiccups

headache

nicotine

nausea

nicotine

nausea

Nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

nausea

nicotine

headache

nicotine

headache

Nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

headache

nicotine

hiccups

nicotine

hiccups

Nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups

nicotine

hiccups


Input: Development of levodopa - induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and / or duration of symptoms. Levodopa - induced dyskinesias (LIDs) present a major problem for the long - term management of Parkinson' s disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP - induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short - term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long - term MPTP exposure, slow symptom progression and / or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e. g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.

levodopa

Levodopa

MPTP

levodopa

MPTP

levodopa

levodopa

MPTP

levodopa

levodopa

levodopa

levodopa

dyskinesias

parkinsonian

dyskinesias

LIDs

Parkinson' s disease

PD

LIDs

parkinsonism

LIDs

dyskinesia

LIDs

dyskinesia

LIDs

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

LIDs

Levodopa

LIDs

Levodopa

LIDs

Levodopa

dyskinesia

Levodopa

LIDs

Levodopa

dyskinesia

Levodopa

LIDs

Levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

LIDs

levodopa

LIDs

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

dyskinesia

levodopa

LIDs

levodopa

LIDs

MPTP

parkinsonism

MPTP

parkinsonism

MPTP

parkinsonism


Input: Propylthiouracil - induced perinuclear - staining antineutrophil cytoplasmic autoantibody - positive vasculitis in conjunction with pericarditis. OBJECTIVE: To describe a case of propylthiouracil - induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25 - year - old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear - staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1 - month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti - MPO pANCA - positive vasculitis associated with propylthio - uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug - induced vasculitis attributable to propylthio - uracil therapy.

Propylthiouracil

propylthiouracil

propylthiouracil

Propylthiouracil

prednisone

propylthio - uracil

propylthio - uracil

vasculitis

pericarditis

vasculitis

pericarditis

hyperthyroidism

pericarditis

fever

glomerulonephritis

Graves' disease

febrile illness

pericarditis

pericarditis

vasculitis

Pericarditis

vasculitis

Propylthiouracil

fever

Propylthiouracil

febrile illness

propylthiouracil

fever

propylthiouracil

febrile illness

propylthiouracil

fever

propylthiouracil

febrile illness

Propylthiouracil

fever

Propylthiouracil

febrile illness

propylthio - uracil

fever

propylthio - uracil

febrile illness

propylthio - uracil

fever

propylthio - uracil

febrile illness

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

Pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

Pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

pericarditis

propylthiouracil

Pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

pericarditis

Propylthiouracil

Pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

Pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

pericarditis

propylthio - uracil

Pericarditis

Propylthiouracil

glomerulonephritis

propylthiouracil

glomerulonephritis

propylthiouracil

glomerulonephritis

Propylthiouracil

glomerulonephritis

propylthio - uracil

glomerulonephritis

propylthio - uracil

glomerulonephritis


Input: Two mouse lines selected for differential sensitivities to beta - carboline - induced seizures are also differentially sensitive to various pharmacological effects of other GABA (A) receptor ligands. Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i. p. injection of methyl beta - carboline - 3 - carboxylate (beta - CCM), an inverse agonist of the GABA (A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA (A) receptor. We measured diazepam - induced anxiolysis with the elevated plus - maze test, diazepam - induced sedation by recording the vigilance states, and picrotoxin - and pentylenetetrazol - induced seizures after i. p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta - CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA (A) receptor.

beta - carboline

GABA

methyl beta - carboline - 3 - carboxylate

beta - CCM

GABA

benzodiazepine

GABA

diazepam

diazepam

picrotoxin

pentylenetetrazol

beta - CCM

diazepam

picrotoxin

pentylenetetrazol

GABA

seizures

seizures

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

pentylenetetrazol

seizures

pentylenetetrazol

seizures

pentylenetetrazol

seizures

pentylenetetrazol

seizures

pentylenetetrazol

seizures

pentylenetetrazol

seizures

beta - carboline

seizures

beta - carboline

seizures

beta - carboline

seizures

methyl beta - carboline - 3 - carboxylate

seizures

methyl beta - carboline - 3 - carboxylate

seizures

methyl beta - carboline - 3 - carboxylate

seizures

beta - CCM

seizures

beta - CCM

seizures

beta - CCM

seizures

beta - CCM

seizures

beta - CCM

seizures

beta - CCM

seizures


Input: Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double - blind, crossover, double - dose study. Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N - methyl - D - aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0. 25 mg / kg or 0. 50 mg / kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double - blind, crossover, double - dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini - Mental State Examination (MMSE) (0 - 30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (" empty head ") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0. 50 mg / kg. A significant difference in MMSE was observed at T30 in patients who received 0. 50 mg / kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.

ketamine

morphine

morphine

N - methyl - D - aspartate

NMDA

ketamine

ketamine

morphine

Ketamine

diazepam

ketamine

ketamine

ketamine

Ketamine

morphine

ketamine

cancer

Pain

pain

neuropathic pain

cancer

pain

Pain

nausea

vomiting

confusion

dry mouth

pain

Hallucinations

pain

neuropathic pain

ketamine

Hallucinations

ketamine

Hallucinations

ketamine

Hallucinations

Ketamine

Hallucinations

ketamine

Hallucinations

ketamine

Hallucinations

ketamine

Hallucinations

Ketamine

Hallucinations

ketamine

Hallucinations


Input: Endocrine screening in 1, 022 men with erectile dysfunction: clinical significance and cost - effective strategy. PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1, 022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost - effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng. / ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1, 340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng. / ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng. / ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng. / ml. in 1. 86% of 1, 821 patients, prolactinomas in 7, 0. 38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng. / ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng. / ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng. / ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost - effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and / or testosterone less than 4 ng. / ml.

erectile dysfunction

erectile dysfunction

low sexual desire

gynecomastia

erectile dysfunction

low sexual desire

gynecomastia

hypogonadism

hyperprolactinemia

pituitary tumors

hypothalamic dysfunction

erectile dysfunction

low sexual desire

prolactinoma

prolactinomas

erectile dysfunction

pituitary tumors

low sexual desire

low sexual desire

gynecomastia

testosterone

Testosterone

testosterone

testosterone

testosterone heptylate

bromocriptine

Testosterone

testosterone

testosterone

testosterone

testosterone

testosterone

Bromocriptine

Testosterone

testosterone

testosterone

testosterone

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

Testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire

testosterone

low sexual desire


Input: Thiopentone pretreatment for propofol injection pain in ambulatory patients. This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double - blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2. 5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5 - 15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms. kg - 1. min - 1). Loss of consciousness occurred in 60 - 90 sec. Visual analogue scores (mean + / - SD) during induction were lower in Groups L (3. 3 + / - 2. 5) and T (4. 1 + / - 2. 7) than in Group C (5. 6 + / - 2. 3); P = 0. 0031. The incidence of venous discomfort was lower in Group L (76. 6%; P < 0. 05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0. 7045; P < 0. 0001). Recovery room discharge times were similar: C (75. 9 + / - 19. 4 min); L 73. 6 + / - 21. 6 min); T (77. 1 + / - 18. 9 min). Assessing their overall satisfaction, 89. 7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.

Thiopentone

propofol

propofol

propofol

lidocaine

thiopentone

propofol

propofol

lidocaine

propofol

thiopentone

pain

pain

Loss of consciousness

pain

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain

propofol

pain


Input: Comparison of i. v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children. The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg - 1 and atropine 10 and 20 micrograms kg - 1 i. v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min - 1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg - 1 or atropine 20 micrograms kg - 1 i. v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.

glycopyrrolate

atropine

suxamethonium

glycopyrrolate

atropine

suxamethonium

glycopyrrolate

atropine

glycopyrrolate

atropine

suxamethonium

bradycardia

arrhythmias

arrhythmia

bradycardia

bradycardia

Bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

Bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

Bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

bradycardia

suxamethonium

Bradycardia


Input: Reduction in caffeine toxicity by acetaminophen. A patient who allegedly consumed 100 tablets of an over - the - counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms / mL) reduced the CNS toxicity of caffeine. Studies in DBA / 2J mice showed that: 1) pretreatment with acetaminophen (100 mg / kg) increased the interval between the administration of caffeine (300 to 450 mg / kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg / kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12. 5 to 75 mg / kg IP). The frequency of sound - induced seizures after 12. 5 or 25 mg / kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg / kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms / mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.

caffeine

acetaminophen

sodium acetylsalicylate

caffeine

acetaminophen

caffeine

caffeine

acetaminophen

caffeine

acetaminophen

caffeine

acetaminophen

caffeine

caffeine

acetaminophen

caffeine

acetaminophen

pentylenetetrezol

Acetaminophen

adenosine

ATP

acetaminophen

caffeine

toxicity

toxicity

convulsions

seizures

seizures

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

caffeine

convulsions

caffeine

seizures

caffeine

seizures

caffeine

seizures

pentylenetetrezol

convulsions

pentylenetetrezol

seizures

pentylenetetrezol

seizures

pentylenetetrezol

seizures


Input: Flestolol: an ultra - short - acting beta - adrenergic blocking agent. Flestolol (ACC - 9089) is a nonselective, competitive, ultra - short - acting beta - adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half - life of approximately 6. 5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms / kg / min. In long - term infusion studies, flestolol was well tolerated at the effective beta - blocking dose (5 micrograms / kg / min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta - adrenergic blockade. Flestolol produced a dose - dependent attenuation of isoproterenol - induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol - induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half - life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well - tolerated, ultra - short - acting beta - adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.

Flestolol

Flestolol

ACC - 9089

Flestolol

flestolol

Flestolol

flestolol

Flestolol

isoproterenol

flestolol

flestolol

Flestolol

flestolol

flestolol

flestolol

tachycardia

supraventricular tachyarrhythmia

unstable angina

chest pain

isoproterenol

tachycardia


Input: Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension. The effect of a 6 - week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two - kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 + / - 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril - treated (n = 8), or nitrendipine - treated (n = 10). Sham - operated rats served as normotensive controls (128 + / - 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine - treated group albuminuria increased from 12. 8 + / - 2 progressively to 163 + / - 55 compared with 19. 2 + / - 9 mg / 24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine - treated group compared with the hypertensive controls (0. 38 + / - 0. 1 versus 0. 13 + / - 0. 04). In addition, glomerular size was higher in the nitrendipine - treated group (14. 9 + / - 0. 17 10 (- 3) mm2) but lower in the enalapril - treated group (11. 5 + / - 0. 15 10 (- 3) mm2) compared with the hypertensive controls (12. 1 + / - 0. 17 10 (- 3) mm2). (ABSTRACT TRUNCATED AT 250 WORDS)

calcium

nitrendipine

calcium

nitrendipine

angiotensin

enalapril

enalapril

nitrendipine

Enalapril

nitrendipine

enalapril

nitrendipine

nitrendipine

nitrendipine

enalapril

nephrosclerosis

renovascular hypertension

albuminuria

renovascular hypertension

hypertensive

hypertensive

glomerulosclerosis

albuminuria

hypertensive

glomerulosclerosis

hypertensive

hypertensive

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

albuminuria

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis

nitrendipine

nephrosclerosis


Input: Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes. Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty - two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.

tinnitus

Idiopathic subjective tinnitus

IST

IST

tinnitus

tinnitus

tinnitus

vertigo

vomiting

tinnitus

lignocaine

lidocaine

lignocaine

lidocaine

lignocaine

vertigo

lidocaine

vertigo

lignocaine

vertigo

lidocaine

vertigo

lignocaine

vomiting

lidocaine

vomiting

lignocaine

vomiting

lidocaine

vomiting


Input: Perhexiline maleate and peripheral neuropathy. Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.

Perhexiline maleate

perhexiline maleate

peripheral neuropathy

Peripheral neuropathy

angina pectoris

demyelinating disorder

neuropathy

Perhexiline maleate

demyelinating disorder

perhexiline maleate

demyelinating disorder

Perhexiline maleate

peripheral neuropathy

Perhexiline maleate

Peripheral neuropathy

perhexiline maleate

peripheral neuropathy

perhexiline maleate

Peripheral neuropathy