Input: A pyridoxine - dependent behavioral disorder unmasked by isoniazid. A 3 - year - old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.

pyridoxine

isoniazid

isoniazid

pyridoxine hydrochloride

isoniazid

pyridoxine

niacinamide

pyridoxine

pyridoxine

pyridoxal

kynurenine

tryptophan

pyridoxine

behavioral disorder

behavioral deterioration

hyperkinesis

irritability

sleeping difficulties

hyperkinesis

isoniazid

hyperkinesis

isoniazid

hyperkinesis

isoniazid

hyperkinesis

isoniazid

hyperkinesis

isoniazid

hyperkinesis

isoniazid

hyperkinesis

isoniazid

behavioral disorder

isoniazid

behavioral deterioration

isoniazid

behavioral disorder

isoniazid

behavioral deterioration

isoniazid

behavioral disorder

isoniazid

behavioral deterioration


Input: A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile. NRA0160, 5 - [2 - (4 - (3 - fluorobenzylidene) piperidin - 1 - yl) ethyl] - 4 - (4 - fluorophenyl) thiazole - 2 - carboxamide, has a high affinity for human cloned dopamine D4. 2, D4. 4 and D4. 7 receptors, with Ki values of 0. 5, 0. 9 and 2. 7 nM, respectively. NRA0160 is over 20, 000fold more potent at the dopamine D4. 2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki = 39 nM), rat serotonin (5 - HT) 2A receptors (Ki = 180 nM) and rat alpha1 adrenoceptor (Ki = 237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP - induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP) - induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.

dopamine

5 - [2 - (4 - (3 - fluorobenzylidene) piperidin - 1 - yl) ethyl] - 4 - (4 - fluorophenyl) thiazole - 2 - carboxamide

dopamine

dopamine

dopamine

dopamine

serotonin

5 - HT

clozapine

methamphetamine

MAP

clozapine

MAP

clozapine

clozapine

apomorphine

clozapine

phencyclidine

PCP

hyperactivity

catalepsy

methamphetamine

hyperactivity

MAP

hyperactivity

MAP

hyperactivity

clozapine

catalepsy

clozapine

catalepsy

clozapine

catalepsy

clozapine

catalepsy

clozapine

catalepsy

catalepsy

catalepsy

5 - [2 - (4 - (3 - fluorobenzylidene) piperidin - 1 - yl) ethyl] - 4 - (4 - fluorophenyl) thiazole - 2 - carboxamide

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy


Input: Prolonged cholestasis after troleandomycin - induced acute hepatitis. We report the case of a patient in whom troleandomycin - induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin - induced acute hepatitis.

cholestasis

hepatitis

hepatitis

cholestasis

Jaundice

hypereosinophilia

Jaundice

cholestasis

pruritus

pruritus

hepatitis

cholestasis

hepatitis

troleandomycin

troleandomycin

troleandomycin

troleandomycin

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

cholestasis

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

Jaundice

troleandomycin

hypereosinophilia

troleandomycin

hypereosinophilia

troleandomycin

hypereosinophilia

troleandomycin

hypereosinophilia

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

pruritus

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis

troleandomycin

hepatitis


Input: HMG CoA reductase inhibitors. Current clinical experience. Lovastatin and simvastatin are the 2 best - known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL - cholesterol of 40% in clinical studies. Modest increases in HDL - cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well - tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.

Lovastatin

simvastatin

lovastatin

simvastatin

Lovastatin

cholesterol

cholesterol

cholesterol

creatine

lovastatin

cyclosporin

gemfibrozil

niacin

Lovastatin

simvastatin

cholesterol

Myopathy

myoglobinuria

renal failure

hypercholesterolaemia

gemfibrozil

Myopathy

cyclosporin

Myopathy

Lovastatin

renal failure

lovastatin

renal failure

Lovastatin

renal failure

lovastatin

renal failure

Lovastatin

renal failure

niacin

Myopathy

Lovastatin

myoglobinuria

lovastatin

myoglobinuria

Lovastatin

myoglobinuria

lovastatin

myoglobinuria

Lovastatin

myoglobinuria


Input: Sulfasalazine - induced lupus erythematosus. Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43 - year - old man, who was receiving long - term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six - week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine - induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine - induced lupus syndrome.

Sulfasalazine

sulfasalazine

sulfasalazine

sulfasalazine

sulfasalazine

sulfasalazine

lupus erythematosus

Pneumonitis

pleural effusions

cardiac tamponade

ulcerative colitis

lupus

serositis

inflammatory bowel disease

lupus syndrome

Sulfasalazine

pleural effusions

sulfasalazine

pleural effusions

sulfasalazine

pleural effusions

sulfasalazine

pleural effusions

sulfasalazine

pleural effusions

sulfasalazine

pleural effusions

Sulfasalazine

Pneumonitis

sulfasalazine

Pneumonitis

sulfasalazine

Pneumonitis

sulfasalazine

Pneumonitis

sulfasalazine

Pneumonitis

sulfasalazine

Pneumonitis

Sulfasalazine

lupus erythematosus

Sulfasalazine

lupus

Sulfasalazine

lupus syndrome

sulfasalazine

lupus erythematosus

sulfasalazine

lupus

sulfasalazine

lupus syndrome

sulfasalazine

lupus erythematosus

sulfasalazine

lupus

sulfasalazine

lupus syndrome

sulfasalazine

lupus erythematosus

sulfasalazine

lupus

sulfasalazine

lupus syndrome

sulfasalazine

lupus erythematosus

sulfasalazine

lupus

sulfasalazine

lupus syndrome

sulfasalazine

lupus erythematosus

sulfasalazine

lupus

sulfasalazine

lupus syndrome

Sulfasalazine

cardiac tamponade

sulfasalazine

cardiac tamponade

sulfasalazine

cardiac tamponade

sulfasalazine

cardiac tamponade

sulfasalazine

cardiac tamponade

sulfasalazine

cardiac tamponade


Input: Optimization of levodopa therapy. While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25 / 100 or controlled - release formula, following the general rule not to attempt to titrate carbidopa - levodopa to the point of " normality, " which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects - - such as gastrointestinal disorders, orthostatic hypotension, levodopa - induced psychosis, sleep disturbances or parasomnias, or drug interactions - - also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson' s disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.

levodopa

levodopa

carbidopa

levodopa

dopamine

levodopa

toxicity

gastrointestinal disorders

orthostatic hypotension

psychosis

sleep disturbances

parasomnias

Parkinson' s disease

levodopa

parasomnias

levodopa

parasomnias

levodopa

parasomnias

levodopa

parasomnias

levodopa

gastrointestinal disorders

levodopa

gastrointestinal disorders

levodopa

gastrointestinal disorders

levodopa

gastrointestinal disorders

levodopa

orthostatic hypotension

levodopa

orthostatic hypotension

levodopa

orthostatic hypotension

levodopa

orthostatic hypotension


Input: Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia. Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of' alpha coma', showing non - reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non - reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo - thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.

coma

cerebral hypoxia

comatose

stuporous

withdrawal symptoms

overdose

overdose

coma

neurological sequelae

depression

coma

hypoxaemia

chlormethiazole

alcohol

nitrazepam

nitrazepam

chlormethiazole

chlormethiazole

chlormethiazole

coma

chlormethiazole

comatose

chlormethiazole

coma

chlormethiazole

coma

chlormethiazole

coma

chlormethiazole

comatose

chlormethiazole

coma

chlormethiazole

coma

chlormethiazole

coma

chlormethiazole

comatose

chlormethiazole

coma

chlormethiazole

coma

nitrazepam

coma

nitrazepam

comatose

nitrazepam

coma

nitrazepam

coma

nitrazepam

coma

nitrazepam

comatose

nitrazepam

coma

nitrazepam

coma

chlormethiazole

stuporous

chlormethiazole

stuporous

chlormethiazole

stuporous

nitrazepam

overdose

nitrazepam

overdose

nitrazepam

overdose

nitrazepam

overdose


Input: Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery. BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double - blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and / or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl - dexamethasone, respectively, to 5% (P = 0. 013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0. 0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0. 049 and P = 0. 035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0. 034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane - sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.

fentanyl

sevoflurane

sevoflurane

Fentanyl

sevoflurane

fentanyl

dexamethasone

fentanyl

fentanyl

fentanyl

fentanyl

dexamethasone

Dexamethasone

fentanyl

fentanyl

Fentanyl

sevoflurane

fentanyl

sevoflurane

nausea

vomiting

pain

postoperative nausea and vomiting

postoperative nausea and vomiting

pain

postoperative nausea and vomiting

vomiting

nausea

postoperative nausea and vomiting

postoperative nausea and vomiting

nausea

nausea

Pain

respiratory depression

hypotension

bradycardia

postoperative nausea and vomiting

postoperative pain

fentanyl

hypotension

Fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

fentanyl

hypotension

Fentanyl

hypotension

fentanyl

hypotension

fentanyl

respiratory depression

Fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

respiratory depression

Fentanyl

respiratory depression

fentanyl

respiratory depression

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

Fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

postoperative nausea and vomiting

fentanyl

bradycardia

Fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

fentanyl

bradycardia

Fentanyl

bradycardia

fentanyl

bradycardia


Input: Renal Fanconi syndrome and myopathy after liver transplantation: drug - related mitochondrial cytopathy? Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15 - yr - old girl who had orthotopic liver transplantation because of Wilson' s disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow - up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post - transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow - up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient' s tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.

Renal Fanconi syndrome

myopathy

mitochondrial cytopathy

Wilson' s disease

hepatitis B infection

renal Fanconi syndrome

metabolic acidosis

hypophosphatemia

glycosuria

aminoaciduria

acidosis

acidosis

muscle weakness

Fanconi syndrome

myopathy

mitochondrial disorders

tubular dysfunction

myopathy

mitochondrial dysfunction

Tacrolimus

MMF

steroids

Lamivudine

tacrolimus

sirolimus

tacrolimus

lamivudine

Tacrolimus

Renal Fanconi syndrome

Tacrolimus

renal Fanconi syndrome

Tacrolimus

Fanconi syndrome

Tacrolimus

tubular dysfunction

tacrolimus

Renal Fanconi syndrome

tacrolimus

renal Fanconi syndrome

tacrolimus

Fanconi syndrome

tacrolimus

tubular dysfunction

tacrolimus

Renal Fanconi syndrome

tacrolimus

renal Fanconi syndrome

tacrolimus

Fanconi syndrome

tacrolimus

tubular dysfunction

Tacrolimus

myopathy

Tacrolimus

myopathy

Tacrolimus

myopathy

tacrolimus

myopathy

tacrolimus

myopathy

tacrolimus

myopathy

tacrolimus

myopathy

tacrolimus

myopathy

tacrolimus

myopathy

Lamivudine

myopathy

Lamivudine

myopathy

Lamivudine

myopathy

lamivudine

myopathy

lamivudine

myopathy

lamivudine

myopathy

Lamivudine

Renal Fanconi syndrome

Lamivudine

renal Fanconi syndrome

Lamivudine

Fanconi syndrome

Lamivudine

tubular dysfunction

lamivudine

Renal Fanconi syndrome

lamivudine

renal Fanconi syndrome

lamivudine

Fanconi syndrome

lamivudine

tubular dysfunction


Input: Antipsychotic - like profile of thioperamide, a selective H3 - receptor antagonist in mice. Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H (3) - receptor ligands on neuroleptic - induced catalepsy, apomorphine - induced climbing behavior and amphetamine - induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg / kg p. o.), while apomorphine (1. 5 mg / kg s. c.) and amphetamine (2 mg / kg s. c.) were used for studying climbing behavior and locomotor activities, respectively. (R) - alpha - methylhistamine (RAMH) (5 microg i. c. v.) and thioperamide (THP) (15 mg / kg i. p.), per se did not cause catalepsy. Administration of THP (3. 75, 7. 5 and 15 mg / kg i. p.) 1 h prior to haloperidol resulted in a dose - dependent increase in the catalepsy times (P < 0. 05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg / kg i. p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg / kg i. p.) per se had no effect on these parameters. On amphetamine - induced hyperactivity, THP (3. 75 and 7. 5 mg / kg i. p.) reduced locomotor time, distance traveled and average speed (P < 0. 05). Pretreatment with RAMH (5 microg i. c. v.) could partially reverse such effects of THP (3. 75 mg / kg i. p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic - like profile by potentiating haloperidol - induced catalepsy, reducing amphetamine - induced hyperactivity and reducing apomorphine - induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H (3) - receptors. Findings suggest a potential for H (3) - receptor antagonists in improving the refractory cases of schizophrenia.

thioperamide

histamine

apomorphine

amphetamine

haloperidol

apomorphine

amphetamine

(R) - alpha - methylhistamine

RAMH

thioperamide

THP

THP

haloperidol

RAMH

THP

RAMH

THP

amphetamine

THP

RAMH

THP

apomorphine

THP

RAMH

THP

haloperidol

amphetamine

apomorphine

THP

RAMH

histamine

schizophrenia

catalepsy

Catalepsy

catalepsy

catalepsy

hyperactivity

catalepsy

hyperactivity

schizophrenia

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

thioperamide

catalepsy

thioperamide

Catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

Catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy


Input: Transient platypnea - orthodeoxia - like syndrome induced by propafenone overdose in a young woman with Ebstein' s anomaly. In this report we describe the case of a 37 - year - old white woman with Ebstein' s anomaly, who developed a rare syndrome called platypnea - orthodeoxia, characterized by massive right - to - left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right - to - left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.

platypnea - orthodeoxia - like syndrome

overdose

Ebstein' s anomaly

Ebstein' s anomaly

platypnea - orthodeoxia

hypoxia

cyanosis

patent foramen ovale

overdose

biventricular dysfunction

hypotension

propafenone

propafenone

propafenone

biventricular dysfunction

propafenone

biventricular dysfunction

propafenone

hypoxia

propafenone

hypoxia

propafenone

cyanosis

propafenone

cyanosis


Input: A Phase II trial of cisplatin plus WR - 2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188). BACKGROUND: Cisplatin has minimal antitumor activity when used as second - or third - line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60 - 120 mg / m2 of cisplatin is administered every 3 - 4 weeks. Although a dose - response effect has been observed with cisplatin, the dose - limiting toxicities associated with cisplatin (e. g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR - 2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin - induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg / m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg / m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty - four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life - threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor - protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.

cisplatin

WR - 2721

amifostine

Cisplatin

cisplatin

cisplatin

cisplatin

WR - 2721

amifostine

Amifostine

alkylating agents

cisplatin

cisplatin

amifostine

cisplatin

cisplatin

amifostine

amifostine

amifostine

cisplatin

mannitol

cisplatin

cisplatin

amifostine

amifostine

cisplatin

breast carcinoma

breast carcinoma

toxicities

nephrotoxicity

ototoxicity

neurotoxicity

breast carcinoma

nephrotoxicity

ototoxicity

neuropathy

breast carcinoma

Neurologic toxicity

toxicities

tumor

toxicity

cisplatin

neuropathy

Cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

neuropathy

cisplatin

ototoxicity

cisplatin

ototoxicity

Cisplatin

ototoxicity

Cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

ototoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

Cisplatin

nephrotoxicity

Cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity

cisplatin

nephrotoxicity


Input: Warfarin - induced iliopsoas hemorrhage with subsequent femoral nerve palsy. We present the case of a 28 - year - old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant - induced femoral nerve palsy represents the most common form of warfarin - induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.

Warfarin

warfarin

warfarin

hemorrhage

femoral nerve palsy

muscle tear

pain

contracture

hematoma

nerve entrapment

femoral nerve palsy

partial loss of quadriceps functions

femoral nerve palsy

peripheral neuropathy

pain

motor and sensory impairment

contracture

Warfarin

femoral nerve palsy

Warfarin

femoral nerve palsy

Warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

warfarin

femoral nerve palsy

Warfarin

nerve entrapment

warfarin

nerve entrapment

warfarin

nerve entrapment

Warfarin

muscle tear

Warfarin

partial loss of quadriceps functions

warfarin

muscle tear

warfarin

partial loss of quadriceps functions

warfarin

muscle tear

warfarin

partial loss of quadriceps functions

Warfarin

hematoma

warfarin

hematoma

warfarin

hematoma


Input: Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis. We have described a unique patient who had reversible and dose - related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.

Myasthenia gravis

rheumatoid arthritis

myasthenia gravis

rheumatoid arthritis

penicillamine

chloroquine

penicillamine

chloroquine

acetylcholine

chloroquine

Myasthenia gravis

chloroquine

myasthenia gravis

chloroquine

Myasthenia gravis

chloroquine

myasthenia gravis

penicillamine

Myasthenia gravis

penicillamine

myasthenia gravis

penicillamine

Myasthenia gravis

penicillamine

myasthenia gravis


Input: Nephrotoxicity of combined cephalothin - gentamicin regimen. Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.

Nephrotoxicity

acute tubular necrosis

oliguric renal failure

oliguric

renal failure

nephrotoxicity

renal insufficiency

cephalothin

gentamicin

cephalothin sodium

gentamicin sulfate

gentamicin

acute tubular necrosis

gentamicin sulfate

acute tubular necrosis

cephalothin

acute tubular necrosis

cephalothin sodium

acute tubular necrosis

gentamicin

oliguric renal failure

gentamicin

oliguric

gentamicin sulfate

oliguric renal failure

gentamicin sulfate

oliguric

cephalothin

oliguric renal failure

cephalothin

oliguric

cephalothin sodium

oliguric renal failure

cephalothin sodium

oliguric


Input: Components of lemon essential oil attenuate dementia induced by scopolamine. The anti - dementia effects of s - limonene and s - perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s - perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non - associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle / scopolamine group was significantly lower than that of the vehicle / vehicle group, but this phenomenon was reversed when s - limonene or s - perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.

dementia

dementia

memory impaired

deficit of associative memory

scopolamine

s - limonene

s - perillyl alcohol

scopolamine

s - perillyl alcohol

dopamine

scopolamine

s - limonene

s - perillyl alcohol

scopolamine

scopolamine

memory impaired

scopolamine

deficit of associative memory

scopolamine

memory impaired

scopolamine

deficit of associative memory

scopolamine

memory impaired

scopolamine

deficit of associative memory

scopolamine

memory impaired

scopolamine

deficit of associative memory


Input: The selective 5 - HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat. Antagonists at serotonin type 6 (5 - HT (6)) receptors show activity in models of learning and memory. Although the underlying mechanism (s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive - enhancing effects of the 5 - HT (6) antagonist Ro4368554 (3 - benzenesulfonyl - 7 - (4 - methyl - piperazin - 1 - yl) 1H - indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic - (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time - dependent forgetting task employing a 24 - h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg / kg, p. o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg / kg, intraperitoneally (i. p.)) and metrifonate (10 mg / kg, p. o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg / kg, i. p., and 3 mg / kg, p. o., respectively). In conclusion, although Ro4368554 did not improve a time - related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5 - HT (6) receptor antagonists.

serotonin

5 - HT

acetylcholine

ACh

5 - HT

3 - benzenesulfonyl - 7 - (4 - methyl - piperazin - 1 - yl) 1H - indole

scopolamine

tryptophan

TRP

metrifonate

metrifonate

metrifonate

scopolamine

TRP

5 - HT

memory deficiency

memory deficits

memory deficit

scopolamine

memory deficiency

scopolamine

memory deficits

scopolamine

memory deficit

scopolamine

memory deficiency

scopolamine

memory deficits

scopolamine

memory deficit


Input: Lone atrial fibrillation associated with creatine monohydrate supplementation. Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30 - year - old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid - stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow - up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.

atrial fibrillation

Atrial fibrillation

heart disease

arrhythmia

Thyroid disorders

acute alcohol intoxication

atrial fibrillation

fractures

arrhythmia

creatine

magnesium

potassium

alcohol

creatine

heparin

diltiazem

amiodarone

metoprolol

aspirin

creatine

creatine

creatine

creatine

atrial fibrillation

creatine

Atrial fibrillation

creatine

atrial fibrillation

creatine

atrial fibrillation

creatine

Atrial fibrillation

creatine

atrial fibrillation

creatine

atrial fibrillation

creatine

Atrial fibrillation

creatine

atrial fibrillation

creatine

atrial fibrillation

creatine

Atrial fibrillation

creatine

atrial fibrillation

creatine

atrial fibrillation

creatine

Atrial fibrillation

creatine

atrial fibrillation


Input: Comparison of developmental toxicity of selective and non - selective cyclooxygenase - 2 inhibitors in CRL: (WI) WUBR Wistar rats - - DFU and piroxicam study. BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non - selective (piroxicam) and selective (DFU; 5, 5 - dimethyl - 3 - (3 - fluorophenyl) - 4 - (4 - methylsulphonyl) phenyl - 2 (5H) - furanon) COX - 2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1 = plug day). Doses were set at 0. 3, 3. 0 and 30. 0mg / kg for piroxicam and 0. 2, 2. 0 and 20. 0mg / kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non - selective COX - 2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU - exposed groups. Prenatal exposure to non - selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX - 2 inhibitors. CONCLUSION: Both selective and non - selective COX - 2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX - 2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non - selective drugs and historic control.

toxicity

toxicity

toxicity

ventricular septal (VSD) and midline (MD) defects

ventricular septal (VSD) and midline (MD) defects

and midline (MD) defects

toxicity

intrauterine growth retardation

increase of external and skeletal variations

toxicity

ventricular septal and midline defects

ventricular septal and midline defects

midline defects

DFU

piroxicam

piroxicam

DFU

5, 5 - dimethyl - 3 - (3 - fluorophenyl) - 4 - (4 - methylsulphonyl) phenyl - 2 (5H) - furanon

piroxicam

DFU

piroxicam

piroxicam

DFU

piroxicam

DFU

DFU

piroxicam

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

intrauterine growth retardation

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

piroxicam

increase of external and skeletal variations

DFU

intrauterine growth retardation

DFU

intrauterine growth retardation

5, 5 - dimethyl - 3 - (3 - fluorophenyl) - 4 - (4 - methylsulphonyl) phenyl - 2 (5H) - furanon

intrauterine growth retardation

DFU

intrauterine growth retardation

DFU

intrauterine growth retardation

DFU

intrauterine growth retardation

DFU

intrauterine growth retardation


Input: Protective efficacy of neuroactive steroids against cocaine kindled - seizures in mice. Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma - aminobutyric acid (GABA (A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha - hydroxy - 5alpha - pregnan - 20 - one), pregnanolone (3alpha - hydroxy - 5beta - pregnan - 20 - one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha - hydroxy - 3beta - methyl - 5alpha - pregnan - 20 - one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine - kindled seizures in male, Swiss - Webster mice. Kindled seizures were induced by daily administration of 60 mg / kg cocaine for 5 days. All of these positive GABA (A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.

steroids

cocaine

steroids

steroid

gamma - aminobutyric acid

GABA

cocaine

cocaine

Allopregnanolone

3alpha - hydroxy - 5alpha - pregnan - 20 - one

pregnanolone

3alpha - hydroxy - 5beta - pregnan - 20 - one

ganaxolone

allopregnanolone

3alpha - hydroxy - 3beta - methyl - 5alpha - pregnan - 20 - one

cocaine

cocaine

GABA

allopregnanolone

ganaxolone

Allopregnanolone

pregnanolone

ganaxolone

steroids

cocaine

seizures

neurological and psychiatric disorders

neurological and psychiatric disorders

psychiatric disorders

seizures

drug dependence

seizure

seizures

seizures

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizure

cocaine

seizures

cocaine

seizures

cocaine

seizures


Input: Kidney function and morphology after short - term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat. BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague - Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg / kg / day (given orally), FK506 3. 0 mg / kg / day (given orally) or SRL 0. 4 mg / kg / day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague - Dawley rats. In the' conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr (EDTA). The morphological analysis of the kidneys included a semi - quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi - quantitative scoring was significantly worst in the group treated with CsA plus SRL (P < 0. 001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P < 0. 02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P = 0. 05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.

cyclosporine A

tacrolimus

sirolimus

Sirolimus

SRL

SRL

SRL

cyclosporine A

CsA

tacrolimus

SRL

CsA

SRL

CsA

SRL

CsA

SRL

SRL

CsA

SRL

SRL

CsA

SRL

SRL

nephrotoxic

nephrotoxic

nephrotoxic

fibrosis

fibrosis

fibrosis

fibrosis

fibrosis

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

cyclosporine A

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

CsA

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

tacrolimus

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

nephrotoxic

sirolimus

nephrotoxic

sirolimus

nephrotoxic

sirolimus

nephrotoxic

sirolimus

nephrotoxic

Sirolimus

nephrotoxic

Sirolimus

nephrotoxic

Sirolimus

nephrotoxic

Sirolimus

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic

SRL

nephrotoxic


Input: Effect of fucoidan treatment on collagenase - induced intracerebral hemorrhage in rats. Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h - 1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan - treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti - inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.

fucoidan

fucoidan

fucoidan

Fucoidan

intracerebral hemorrhage

brain damage

ischemic stroke

Intracerebral hemorrhage

inflammation

ischemic stroke

brain damage

intracerebral hemorrhage

hematoma

impaired blood clotting

hemodilution

hematomas

inflammation

hematoma

hemorrhage

white matter edema

neuronal loss

hematoma

intracerebral hemorrhage

fucoidan

impaired blood clotting

fucoidan

hemodilution

fucoidan

impaired blood clotting

fucoidan

hemodilution

fucoidan

impaired blood clotting

fucoidan

hemodilution

Fucoidan

impaired blood clotting

Fucoidan

hemodilution

fucoidan

white matter edema

fucoidan

white matter edema

fucoidan

white matter edema

Fucoidan

white matter edema


Input: Paracetamol - associated coma, metabolic acidosis, renal and hepatic failure. A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.

Paracetamol

paracetamol

coma

metabolic acidosis

renal and hepatic failure

renal and hepatic failure

hepatic failure

metabolic acidosis

acute renal failure and hepatic failure

acute renal failure

acute renal failure and hepatic failure

Paracetamol

metabolic acidosis

Paracetamol

metabolic acidosis

paracetamol

metabolic acidosis

paracetamol

metabolic acidosis

Paracetamol

acute renal failure and hepatic failure

Paracetamol

acute renal failure and hepatic failure

paracetamol

acute renal failure and hepatic failure

paracetamol

acute renal failure and hepatic failure

Paracetamol

renal and hepatic failure

Paracetamol

renal and hepatic failure

Paracetamol

acute renal failure

paracetamol

renal and hepatic failure

paracetamol

renal and hepatic failure

paracetamol

acute renal failure


Input: Hepatic reactions associated with ketoconazole in the United Kingdom. Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57. 9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3. 1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.

ketoconazole

Ketoconazole

ketoconazole

ketoconazole

hepatotoxicity

deaths

deaths

hepatotoxicity

jaundice

hepatocellular injury

cholestasis

rash

eosinophilia

Hepatitis

deaths

jaundice

hepatitis

hepatitis

hepatic injury

ketoconazole

jaundice

ketoconazole

jaundice

Ketoconazole

jaundice

Ketoconazole

jaundice

ketoconazole

jaundice

ketoconazole

jaundice

ketoconazole

jaundice

ketoconazole

jaundice

ketoconazole

cholestasis

Ketoconazole

cholestasis

ketoconazole

cholestasis

ketoconazole

cholestasis

ketoconazole

hepatotoxicity

ketoconazole

hepatotoxicity

ketoconazole

hepatocellular injury

ketoconazole

Hepatitis

ketoconazole

hepatitis

ketoconazole

hepatitis

ketoconazole

hepatic injury

Ketoconazole

hepatotoxicity

Ketoconazole

hepatotoxicity

Ketoconazole

hepatocellular injury

Ketoconazole

Hepatitis

Ketoconazole

hepatitis

Ketoconazole

hepatitis

Ketoconazole

hepatic injury

ketoconazole

hepatotoxicity

ketoconazole

hepatotoxicity

ketoconazole

hepatocellular injury

ketoconazole

Hepatitis

ketoconazole

hepatitis

ketoconazole

hepatitis

ketoconazole

hepatic injury

ketoconazole

hepatotoxicity

ketoconazole

hepatotoxicity

ketoconazole

hepatocellular injury

ketoconazole

Hepatitis

ketoconazole

hepatitis

ketoconazole

hepatitis

ketoconazole

hepatic injury


Input: Combined effects of prolonged prostaglandin E1 - induced hypotension and haemodilution on human hepatic function. Combined effects of prolonged prostaglandin E1 (PGE1) - induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto - acetate / 3 - hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (- 40%) and at 180 min (- 49%) after the start of hypotension and at 60 min (- 32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1 - induced hypotension and moderate haemodilution would cause impairment of hepatic function.

prostaglandin E1

prostaglandin E1

dextran

aceto - acetate

3 - hydroxybutyrate

bilirubin

hypotension

haemodilution

hypotension

haemodilution

hypotension

haemodilution

hypotension

haemodilution

Haemodilution

hypotension

hypotension

hypotension

haemodilution

impairment of hepatic function

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

prostaglandin E1

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

prostaglandin E1

impairment of hepatic function

prostaglandin E1

impairment of hepatic function

impairment of hepatic function

impairment of hepatic function

impairment of hepatic function


Input: Levodopa - induced dyskinesias in patients with Parkinson' s disease: filling the bench - to - bedside gap. Levodopa is the most effective drug for the treatment of Parkinson' s disease. However, the long - term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa - induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson' s disease has provided important information to understand the effect of specific receptor and post - receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non - dopaminergic neurotransmitter systems in the pathophysiology of levodopa - induced dyskinesias.

Levodopa

Levodopa

dopamine

levodopa

dopamine

glutamate

levodopa

dyskinesias

Parkinson' s disease

Parkinson' s disease

dyskinesias

dyskinesias

Parkinson' s disease

dyskinetic movements

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinetic movements

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinesias

Levodopa

dyskinetic movements

Levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinetic movements

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinesias

levodopa

dyskinetic movements

levodopa

dyskinesias


Input: Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy. In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine' s seizure severity scale. All of the rats in the saline - treated epileptic control group developed SRS, whereas none of the BMC - treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long - term chronic phase (120 days after transplantation), only 25% of BMC - treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral - CA1 synapses, long - term potentiation was preserved in BMC - transplanted rats compared to epileptic controls. The donor - derived GFP (+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.

seizures

epilepsy

epilepsy

status epilepticus

SE

Spontaneous recurrent seizures

SRS

seizure

epileptic

SRS

epileptic

seizures

epileptic

seizures

epileptic

epileptic

epileptic

seizures

neuronal loss

pilocarpine

pilocarpine

epilepsy

pilocarpine

epilepsy

pilocarpine

epileptic

pilocarpine

epileptic

pilocarpine

epileptic

pilocarpine

epileptic

pilocarpine

epileptic

pilocarpine

epileptic

pilocarpine

status epilepticus

pilocarpine

SE


Input: Cardioprotective effect of salvianolic acid A on isoproterenol - induced myocardial infarction in rats. The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol - induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol - treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end - diastolic pressure and ST - segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP / O was observed in isoproterenol - treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol - induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol - induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol - induced myocardial infarction.

salvianolic acid A

isoproterenol

salvianolic acid A

isoproterenol

Isoproterenol

lactate

aspartate

creatine

malondialdehyde

superoxide

glutathione

ADP

isoproterenol

salvianolic acid A

isoproterenol

salvianolic acid A

isoproterenol

salvianolic acid A

isoproterenol

myocardial infarction

myocardial infarction

respiratory dysfunction

cardiac dysfunction

myocardial injury

myocardial damage

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

Isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction

isoproterenol

myocardial infarction


Input: Acute effects of N - (2 - propylpentanoyl) urea on hippocampal amino acid neurotransmitters in pilocarpine - induced seizure in rats. The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N - (2 - propylpentanoyl) urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED (50)) of 49 mg / kg in protecting rats against pilocarpine - induced seizure whereas the corresponding value for VPA was 322 mg / kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg / kg) or VPA (300 and 600 mg / kg) completely abolished pilocarpine - evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine - induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine - induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine - induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.

N - (2 - propylpentanoyl) urea

amino acid

pilocarpine

amino acid

glutamate

aspartate

glycine

GABA

N - (2 - propylpentanoyl) urea

VPU

valproic acid

VPA

VPU

VPA

pilocarpine

VPA

pilocarpine

glutamate

aspartate

glycine

GABA

VPU

VPA

pilocarpine

glutamate

aspartate

GABA

glycine

glutamate

aspartate

VPU

VPA

pilocarpine

amino acid

glutamate

aspartate

VPA

VPU

pilocarpine

glutamate

aspartate

pilocarpine

seizure

seizure

seizure

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure

pilocarpine

seizure


Input: Acute hepatitis attack after exposure to telithromycin. INTRODUCTION: Antibiotic - associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25 - year - old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg / d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U / L (reference range, 10 - 37 U / L); aspartate aminotransferase, 98 U / L (10 - 40 U / L); alkaline phosphatase, 513 U / L (0 - 270 U / L); gamma - glutamyltransferase, 32 U / L (7 - 49 U / L); amylase, 46 U / L (0 - 220 U / L); total bilirubin, 20. 1 mg / dL (0. 2 - 1. 0 mg / dL); direct bilirubin, 14. 8 mg / dL (0 - 0. 3 mg / dL); and albumin, 4. 7 mg / dL (3. 5 - 5. 4 mg / dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of " acute hepatitis of unknown origin, " that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug - induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.

hepatitis

hepatotoxicity

hepatic injury

adverse drug reactions

jaundice

nausea

vomiting

upper respiratory tract infection

hepatitis

hepatic dysfunction

adverse drug reaction

hepatitis

toxic hepatitis

hepatitis

hepatitis

telithromycin

telithromycin

alanine

aspartate

bilirubin

bilirubin

alcohol

telithromycin

Telithromycin

telithromycin

telithromycin

telithromycin

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

Telithromycin

hepatitis

Telithromycin

hepatotoxicity

Telithromycin

hepatic injury

Telithromycin

hepatitis

Telithromycin

hepatitis

Telithromycin

toxic hepatitis

Telithromycin

hepatitis

Telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

hepatotoxicity

telithromycin

hepatic injury

telithromycin

hepatitis

telithromycin

hepatitis

telithromycin

toxic hepatitis

telithromycin

hepatitis

telithromycin

hepatitis


Input: Spironolactone - induced renal insufficiency and hyperkalemia in patients with heart failure. BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K (+) > 5. 0 mEq / L) or renal insufficiency (Cr > or = 2. 5 mg / dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow - up time periods were compared. RESULTS: Sixty - seven of 926 patients (7. 2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta - blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone - induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta - blockers.

Spironolactone

spironolactone

spironolactone

spironolactone

spironolactone

K

Cr

spironolactone

potassium

potassium

creatinine

thiazide

Spironolactone

renal insufficiency

hyperkalemia

heart failure

heart failure

hyperkalemia

renal insufficiency

heart failure

hyperkalemia

renal insufficiency

heart failure

heart failure

hyperkalemia

renal insufficiency

hyperkalemia

renal failure

hyperkalemia

diabetes

renal insufficiency

hyperkalemia

renal insufficiency

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

hyperkalemia

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal failure

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal failure

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal failure

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal failure

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal failure

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal insufficiency

spironolactone

renal failure

spironolactone

renal insufficiency

spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency

Spironolactone

renal failure

Spironolactone

renal insufficiency

Spironolactone

renal insufficiency


Input: End - stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin - based immunotherapy: risk of development and treatment. BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end - stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n = 834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n = 748; CRF, sustained serum creatinine > 2. 5 mg / dl, n = 41; and ESRD, n = 45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18. 1% (CRF 8. 6% and ESRD 9. 5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1 - year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2. 6, 2. 2, and 1. 6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28. 2% compared with 54. 6% in the control group. Patients developing ESRD had a 6 - year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71. 4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post - OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1 - year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long - term immunosuppression may be needed to decrease this complication.

End - stage renal disease

ESRD

nephrotoxic

end - stage renal disease

ESRD

ESRD

chronic renal failure

CRF

CRF

ESRD

CRF

ESRD

ESRD

ESRD

renal dysfunction

CRF

ESRD

CRF

ESRD

hepatorenal syndrome

CRF

ESRD

ESRD

ESRD

ESRD

ESRD

CRF

ESRD

ESRD

ESRD

hepatorenal syndrome

CRF

ESRD

cyclosporine

tacrolimus

creatinine

creatinine

creatinine

creatinine

creatinine

creatinine

tacrolimus

nephrotoxic

tacrolimus

renal dysfunction

cyclosporine

nephrotoxic

cyclosporine

renal dysfunction


Input: Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine - induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n = 100), 1 mg / h (low - dose) nimodipine (n = 101), or 2 mg / h (high - dose) nimodipine (n = 94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty - five patients were included in this analysis (n = 92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high - dose group (beta = 0. 49, P = 0. 048). Patients with a DBP reduction of > or = 20% in the high - dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index < 60) (n / N = 25 / 26, OR 10. 16, 95% CI 1. 02 to 101. 74) and death alone (n / N = 9 / 26, OR 4. 336, 95% CI 1. 131 16. 619) compared with all placebo patients (n / N = 62 / 92 and 14 / 92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high - dose nimodipine after acute stroke. For low - dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.

nimodipine

Nimodipine

nimodipine

nimodipine

nimodipine

Nimodipine

nimodipine

nimodipine

nimodipine

acute stroke

Stroke

reduction in blood pressure

acute stroke

BP reduction

ischemic stroke

reduction in systolic BP

DBP reduction

DBP reduction

death

death

acute stroke

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

Nimodipine

reduction in blood pressure

Nimodipine

BP reduction

Nimodipine

reduction in systolic BP

Nimodipine

DBP reduction

Nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

Nimodipine

reduction in blood pressure

Nimodipine

BP reduction

Nimodipine

reduction in systolic BP

Nimodipine

DBP reduction

Nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction

nimodipine

reduction in blood pressure

nimodipine

BP reduction

nimodipine

reduction in systolic BP

nimodipine

DBP reduction

nimodipine

DBP reduction


Input: Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine. BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short - acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double - blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2. 5 ml 2% lidocaine in 7. 5% glucose, 2% prilocaine in 7. 5% glucose, or 0. 5% bupivacaine in 7. 5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0. 03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0. 05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.

Transient neurologic symptoms

transient neurologic symptoms

TNSs

TNSs

TNSs

TNSs

TNSs

TNSs

prilocaine

bupivacaine

lidocaine

lidocaine

bupivacaine

lidocaine

Prilocaine

lidocaine

prilocaine

lidocaine

bupivacaine

lidocaine

glucose

prilocaine

glucose

bupivacaine

glucose

lidocaine

prilocaine

bupivacaine

lidocaine

prilocaine

bupivacaine

Prilocaine

lidocaine

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

Transient neurologic symptoms

lidocaine

transient neurologic symptoms

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

lidocaine

TNSs

prilocaine

Transient neurologic symptoms

prilocaine

transient neurologic symptoms

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

Prilocaine

Transient neurologic symptoms

Prilocaine

transient neurologic symptoms

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

prilocaine

Transient neurologic symptoms

prilocaine

transient neurologic symptoms

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

Transient neurologic symptoms

prilocaine

transient neurologic symptoms

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

Transient neurologic symptoms

prilocaine

transient neurologic symptoms

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

Transient neurologic symptoms

prilocaine

transient neurologic symptoms

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

prilocaine

TNSs

Prilocaine

Transient neurologic symptoms

Prilocaine

transient neurologic symptoms

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs

Prilocaine

TNSs


Input: The role of nicotine in smoking - related cardiovascular disease. Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low - level cigarette exposures.

nicotine

Nicotine

nicotine

nicotine

nicotine

carbon monoxide

Nicotine

nicotine

nicotine

nicotine

nicotine

cardiovascular disease

cardiovascular disease

atherosclerosis

thrombosis

nicotine

cardiovascular disease

nicotine

cardiovascular disease

Nicotine

cardiovascular disease

Nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

Nicotine

cardiovascular disease

Nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

cardiovascular disease

nicotine

atherosclerosis

Nicotine

atherosclerosis

nicotine

atherosclerosis

nicotine

atherosclerosis

nicotine

atherosclerosis

Nicotine

atherosclerosis

nicotine

atherosclerosis

nicotine

atherosclerosis

nicotine

atherosclerosis

nicotine

atherosclerosis