Input: Reduced cardiotoxicity of doxorubicin given in the form of N - (2 - hydroxypropyl) methacrylamide conjugates: and experimental study in the rat. A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg / kg doxorubicin (DOX) given either as free drug or in the form of three N - (2 - hydroxypropyl) methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non - biodegradable (Gly - Gly) or degradable by lysosomal proteinases (Gly - Phe - Leu - Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i. v. administration of free and polymer - bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer - bound DOX (4 mg / kg) was significantly lower than that observed in those that received free DOX (4 mg / kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg / kg; P less than 0. 01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX - induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age - matched control rats (P less than 0. 05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0. 05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0. 01). (ABSTRACT TRUNCATED AT 400 WORDS)

cardiotoxicity

toxicity

cardiotoxicity

cardiotoxicity

cardiotoxicity

doxorubicin

N - (2 - hydroxypropyl) methacrylamide

doxorubicin

DOX

N - (2 - hydroxypropyl) methacrylamide

HPMA

HPMA

DOX

Gly - Phe - Leu - Gly

galactosamine

DOX

DOX

DOX

HPMA

DOX

DOX

HPMA

DOX

DOX

DOX

HPMA

DOX

HPMA

DOX

DOX

HPMA

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity


Input: Topical 0. 025% capsaicin in chronic post - herpetic neuralgia: efficacy, predictors of response and long - term course. In order to evaluate the efficacy, time - course of action and predictors of response to topical capsaicin, 39 patients with chronic post - herpetic neuralgia (PHN), median duration 24 months, were treated with 0. 025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow - up investigation was performed 10 - 12 months after study onset on the patients who had improved. Nineteen patients (48. 7%) substantially improved after the 8 - week trial; 5 (12. 8%) discontinued therapy due to side - effects such as intolerable capsaicin - induced burning sensations (4) or mastitis (1); 15 (38. 5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72. 2% were still improved at the follow - up; only one - third of them had continued application irregularly. Treatment effect was not dependent on patient' s age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time - course or severity of capsaicin - induced burning. If confirmed in controlled trials, the long - term results of this open, non - randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.

capsaicin

capsaicin

capsaicin

capsaicin

capsaicin

capsaicin

post - herpetic neuralgia

post - herpetic neuralgia

PHN

pain

mastitis

PHN

sensory disturbance

pain

PHN

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

pain

capsaicin

mastitis

capsaicin

mastitis

capsaicin

mastitis

capsaicin

mastitis

capsaicin

mastitis

capsaicin

mastitis


Input: Serotonin reuptake inhibitors, paranoia, and the ventral basal ganglia. Antidepressants have previously been associated with paranoid reactions in psychiatric patients. Five cases of paranoid exacerbation with the serotonin reuptake inhibitors fluoxetine and amitriptyline are reported here. Elements common to these cases included a history of paranoid symptomatology and the concomitant occurrence of depressive and psychotic symptoms. Complicated depressive disorders (including atypicality of course and symptomatology, chronicity, psychosis, bipolarity, and secondary onset in the course of a primary psychosis) may present particular vulnerability to paranoid exacerbations associated with serotonin reuptake inhibitors. Although the pharmacology and neurobiology of paranoia remain cryptic, several mechanisms, including 5HT3 receptor - mediated dopamine release, beta - noradrenergic receptor downregulation, or GABAB receptor upregulation acting in the vicinity of the ventral basal ganglia (possibly in lateral orbitofrontal or anterior cingulate circuits), might apply to this phenomenon. These cases call attention to possible paranoid exacerbations with serotonin reuptake blockers in select patients and raise neurobiological considerations regarding paranoia.

Serotonin

serotonin

fluoxetine

amitriptyline

serotonin

dopamine

serotonin

paranoia

paranoid

paranoid

paranoid

depressive and psychotic symptoms

depressive and psychotic symptoms

psychotic symptoms

depressive disorders

psychosis

psychosis

paranoid

paranoia

paranoid

paranoia

fluoxetine

paranoia

fluoxetine

paranoid

fluoxetine

paranoid

fluoxetine

paranoid

fluoxetine

paranoid

fluoxetine

paranoia

fluoxetine

paranoid

fluoxetine

paranoia

amitriptyline

paranoia

amitriptyline

paranoid

amitriptyline

paranoid

amitriptyline

paranoid

amitriptyline

paranoid

amitriptyline

paranoia

amitriptyline

paranoid

amitriptyline

paranoia


Input: Five cases of encephalitis during treatment of loiasis with diethylcarbamazine. Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i. e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti - allergic treatment. This type of drug - induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.

encephalitis

loiasis

encephalitis

filariasis

encephalitis

microfilaremia

diethylcarbamazine

diethylcarbamazine

DEC

DEC

diethylcarbamazine

encephalitis

diethylcarbamazine

encephalitis

diethylcarbamazine

encephalitis

diethylcarbamazine

encephalitis

diethylcarbamazine

encephalitis

diethylcarbamazine

encephalitis

DEC

encephalitis

DEC

encephalitis

DEC

encephalitis

DEC

encephalitis

DEC

encephalitis

DEC

encephalitis


Input: Delirium in an elderly woman possibly associated with administration of misoprostol. Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89 - year - old woman in a long - term care facility became confused after the initiation of misoprostol therapy. The patient' s change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy.

Delirium

headache

delirium

delirium

misoprostol

Misoprostol

misoprostol

misoprostol

misoprostol

misoprostol

Delirium

misoprostol

delirium

misoprostol

delirium

Misoprostol

Delirium

Misoprostol

delirium

Misoprostol

delirium

misoprostol

Delirium

misoprostol

delirium

misoprostol

delirium

misoprostol

Delirium

misoprostol

delirium

misoprostol

delirium

misoprostol

Delirium

misoprostol

delirium

misoprostol

delirium


Input: Hepatocellular oxidant stress following intestinal ischemia - reperfusion injury. Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia - reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia - reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation.

ischemia

reperfusion injury

ischemic

liver dysfunction

hepatic injury

hepatic injury

ischemia

reperfusion injury

ischemia

reperfusion injury

oxidized and reduced glutathione

oxidized and reduced glutathione

reduced glutathione

glutathione

Oxidized glutathione

GSSG

GSSG

GSSG

oxidized and reduced glutathione

reperfusion injury

oxidized and reduced glutathione

reperfusion injury

oxidized and reduced glutathione

reperfusion injury

oxidized and reduced glutathione

reperfusion injury

oxidized and reduced glutathione

reperfusion injury

oxidized and reduced glutathione

reperfusion injury

Oxidized glutathione

reperfusion injury

Oxidized glutathione

reperfusion injury

Oxidized glutathione

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury

GSSG

reperfusion injury


Input: Diphenhydramine prevents the haemodynamic changes of cimetidine in ICU patients. Cimetidine, a histamine 2 (H2) antagonist, produces a decrease in arterial pressure due to vasodilatation, especially in critically ill patients. This may be because cimetidine acts as a histamine agonist. We, therefore, investigated the effects of the histamine 1 (H1) receptor antagonist, diphenhydramine, on the haemodynamic changes observed after cimetidine in ICU patients. Each patient was studied on two separate days. In a random fashion, they received cimetidine 200 mg iv on one day, and on the other, a pretreatment of diphenhydramine 40 mg iv with cimetidine 200 mg iv. In the non - pretreatment group, mean arterial pressure (MAP) decreased from 107. 4 + / - 8. 4 mmHg to 86. 7 + / - 11. 4 mmHg (P less than 0. 01) two minutes after cimetidine. Also, systemic vascular resistance (SVR) decreased during the eight - minute observation period (P less than 0. 01). In contrast, in the pretreatment group, little haemodynamic change was seen. We conclude that an H1 antagonist may be useful in preventing hypotension caused by iv cimetidine, since the vasodilating activity of cimetidine is mediated, in part, through the H1 receptor.

Diphenhydramine

cimetidine

Cimetidine

histamine

cimetidine

histamine

histamine

diphenhydramine

cimetidine

cimetidine

diphenhydramine

cimetidine

cimetidine

cimetidine

cimetidine

hypotension

cimetidine

hypotension

Cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension

cimetidine

hypotension


Input: Acute renal failure due to rifampicin. A 23 - year - old male patient with bacteriologically proven pulmonary tuberculosis was treated with the various regimens of antituberculosis drugs for nearly 15 months. Rifampicin was administered thrice as one of the 3 - 4 drug regimen and each time he developed untoward side effects like nausea, vomiting and fever with chills and rigors. The last such episode was of acute renal failure at which stage the patient was seen by the authors of this report. The patient, however, made a full recovery.

Acute renal failure

pulmonary tuberculosis

nausea

vomiting

fever

rifampicin

Rifampicin

rifampicin

Acute renal failure

Rifampicin

Acute renal failure


Input: Severe polyneuropathy and motor loss after intrathecal thiotepa combination chemotherapy: description of two cases. Two cases of severe delayed neurologic toxicity related to the administration of intrathecal (IT) combination chemotherapy including thiotepa (TSPA) are presented. Both cases developed axonal neuropathy with motor predominance in the lower extremities 1 and 6 months after IT chemotherapy was administered. Neurologic toxicities have been described with IT - methotrexate, IT - cytosine arabinoside and IT - TSPA. To our knowledge, however, axonal neuropathy following administration of these three agents has not been previously described. In spite of the fact that TSPA is a useful IT agent, its combination with MTX, ara - C and radiotherapy could cause severe neurotoxicity. This unexpected complication indicates the need for further toxicology research on IT - TSPA.

polyneuropathy

neurologic toxicity

axonal neuropathy

Neurologic toxicities

axonal neuropathy

neurotoxicity

thiotepa

thiotepa

TSPA

methotrexate

cytosine arabinoside

TSPA

TSPA

MTX

ara - C

TSPA

cytosine arabinoside

polyneuropathy

ara - C

polyneuropathy

methotrexate

polyneuropathy

MTX

polyneuropathy

thiotepa

polyneuropathy

thiotepa

polyneuropathy

TSPA

polyneuropathy

TSPA

polyneuropathy

TSPA

polyneuropathy

TSPA

polyneuropathy

cytosine arabinoside

neurologic toxicity

cytosine arabinoside

Neurologic toxicities

cytosine arabinoside

neurotoxicity

ara - C

neurologic toxicity

ara - C

Neurologic toxicities

ara - C

neurotoxicity

methotrexate

neurologic toxicity

methotrexate

Neurologic toxicities

methotrexate

neurotoxicity

MTX

neurologic toxicity

MTX

Neurologic toxicities

MTX

neurotoxicity

thiotepa

neurologic toxicity

thiotepa

Neurologic toxicities

thiotepa

neurotoxicity

thiotepa

neurologic toxicity

thiotepa

Neurologic toxicities

thiotepa

neurotoxicity

TSPA

neurologic toxicity

TSPA

Neurologic toxicities

TSPA

neurotoxicity

TSPA

neurologic toxicity

TSPA

Neurologic toxicities

TSPA

neurotoxicity

TSPA

neurologic toxicity

TSPA

Neurologic toxicities

TSPA

neurotoxicity

TSPA

neurologic toxicity

TSPA

Neurologic toxicities

TSPA

neurotoxicity


Input: Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs. The effects of i. v. bolus administration of cromakalim (1 - 10 micrograms / kg) and pinacidil (3 - 100 micrograms / kg) on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs and compared to those of nitroglycerin (0. 03 - 10 micrograms / kg). Nitroglycerin, up to 0. 3 micrograms / kg, selectively increased circumflex artery diameter (CxAD) without simultaneously affecting any other cardiac or systemic hemodynamic parameter. In contrast, cromakalim and pinacidil at all doses and nitroglycerin at doses higher than 0. 3 micrograms / kg simultaneously and dose - dependently increased CxAD, coronary blood flow and heart rate and decreased coronary vascular resistance and aortic pressure. Cromakalim was approximately 8 - to 9. 5 - fold more potent than pinacidil in increasing CxAD. Vasodilation of large and small coronary vessels and hypotension induced by cromakalim and pinacidil were not affected by prior combined beta adrenergic and muscarinic receptors blockade but drug - induced tachycardia was abolished. When circumflex artery blood flow was maintained constant, the increases in CxAD induced by cromakalim (10 micrograms / kg), pinacidil (30 micrograms / kg) and nitroglycerin (10 micrograms / kg) were reduced by 68 + / - 7, 54 + / - 9 and 1 + / - 1%, respectively. Thus, whereas nitroglycerin preferentially and flow - independently dilates large coronary arteries, cromakalim and pinacidil dilate both large and small coronary arteries and this effect is not dependent upon the simultaneous beta adrenoceptors - mediated rise in myocardial metabolic demand. Finally, two mechanisms at least, direct vasodilation and flow dependency, are involved in the cromakalim - and pinacidil - induced increase in CxAD.

cromakalim

pinacidil

cromakalim

pinacidil

nitroglycerin

Nitroglycerin

cromakalim

pinacidil

nitroglycerin

Cromakalim

pinacidil

cromakalim

pinacidil

beta adrenergic and muscarinic receptors blockade

beta adrenergic and muscarinic receptors blockade

muscarinic receptors blockade

cromakalim

pinacidil

nitroglycerin

nitroglycerin

cromakalim

pinacidil

cromakalim

pinacidil

hypotension

tachycardia

cromakalim

hypotension

cromakalim

hypotension

cromakalim

hypotension

Cromakalim

hypotension

cromakalim

hypotension

cromakalim

hypotension

cromakalim

hypotension

cromakalim

hypotension

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

pinacidil

tachycardia

cromakalim

tachycardia

cromakalim

tachycardia

cromakalim

tachycardia

Cromakalim

tachycardia

cromakalim

tachycardia

cromakalim

tachycardia

cromakalim

tachycardia

cromakalim

tachycardia

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension

pinacidil

hypotension


Input: Mefenamic acid - induced neutropenia and renal failure in elderly females with hypothyroidism. We report mefenamic acid - induced non - oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

Mefenamic acid

mefenamic acid

mefenamic acid

neutropenia

renal failure

hypothyroidism

renal failure

neutropenia

neutropenia

hypothyroid

hypothyroid

hypothyroidism

Mefenamic acid

neutropenia

Mefenamic acid

neutropenia

Mefenamic acid

neutropenia

mefenamic acid

neutropenia

mefenamic acid

neutropenia

mefenamic acid

neutropenia

mefenamic acid

neutropenia

mefenamic acid

neutropenia

mefenamic acid

neutropenia

Mefenamic acid

renal failure

Mefenamic acid

renal failure

mefenamic acid

renal failure

mefenamic acid

renal failure

mefenamic acid

renal failure

mefenamic acid

renal failure


Input: Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy. Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2. 7 to 3. 8 mmol / L (10. 7 to 15. 0 mg / dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2. 4 + / - 0. 03 to 2. 5 + / - 0. 03 mmol / L [9. 7 + / - 0. 2 to 10. 2 + / - 0. 1 mg / dL], P = 0. 006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2. 3 + / - 0. 05 to 2. 3 + / - 0. 05 mmol / L [9. 2 + / - 0. 2 to 9. 2 + / - 0. 2 mg / dL]). CaCO3 dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups. (ABSTRACT TRUNCATED AT 250 WORDS)

hypercalcemia

hypercalcemic

hypercalcemia

renal disease

hypercalcemic

hypercalcemic

calcium carbonate

calcium carbonate

phosphate

calcium

calcium

calcium

calcium

calcium

vitamin D

bicarbonate

calcium carbonate

hypercalcemia

calcium carbonate

hypercalcemic

calcium carbonate

hypercalcemia

calcium carbonate

hypercalcemic

calcium carbonate

hypercalcemic

calcium carbonate

hypercalcemia

calcium carbonate

hypercalcemic

calcium carbonate

hypercalcemia

calcium carbonate

hypercalcemic

calcium carbonate

hypercalcemic

hypercalcemia

hypercalcemic

hypercalcemia

hypercalcemic

hypercalcemic


Input: Methyldopa - induced hemolytic anemia in a 15 year old presenting as near - syncope. Methyldopa is an antihypertensive medication which is available generically and under the trade name Aldomet that is widely prescribed in the adult population and infrequently used in children. Methyldopa causes an autoimmune hemolytic anemia in a small percentage of patients who take the drug. We report a case of methyldopa - induced hemolytic anemia in a 15 - year - old boy who presented to the emergency department with near - syncope. The boy had been treated with intravenous methyldopa during a trauma admission seven weeks prior to presentation. Evaluation revealed a hemoglobin of three grams, 3 + Coombs' test with polyspecific anti - human globulin and monospecific IgG reagents, and a warm reacting autoantibody. Transfusion and corticosteroid therapy resulted in a complete recovery of the patient. Emergency physicians treating children must be aware of this syndrome in order to diagnose and treat it correctly. A brief review of autoimmune and drug - induced hemolytic anemias is provided.

Methyldopa

Methyldopa

Aldomet

Methyldopa

methyldopa

methyldopa

corticosteroid

hemolytic anemia

syncope

autoimmune hemolytic anemia

hemolytic anemia

emergency department

syncope

trauma

hemolytic anemias

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemias

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemias

Aldomet

hemolytic anemia

Aldomet

hemolytic anemia

Aldomet

hemolytic anemias

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemia

Methyldopa

hemolytic anemias

methyldopa

hemolytic anemia

methyldopa

hemolytic anemia

methyldopa

hemolytic anemias

methyldopa

hemolytic anemia

methyldopa

hemolytic anemia

methyldopa

hemolytic anemias


Input: The long - term safety of danazol in women with hereditary angioedema. Although the short - term safety (less than or equal to 6 months) of danazol has been established in a variety of settings, no information exists as to its long - term safety. We therefore investigated the long - term safety of danazol by performing a retrospective chart review of 60 female patients with hereditary angioedema treated with danazol for a continuous period of 6 months or longer. The mean age of the patients was 35. 2 years and the mean duration of therapy was 59. 7 months. Virtually all patients experienced one or more adverse reactions. Menstrual abnormalities (79%), weight gain (60%), muscle cramps / myalgias (40%), and transaminase elevations (40%) were the most common adverse reactions. The drug was discontinued due to adverse reactions in 8 patients. No patient has died or suffered any apparent long - term sequelae that were directly attributable to the drug. We conclude that, despite a relatively high incidence of adverse reactions, danazol has proven to be remarkably safe over the long - term in this group of patients.

danazol

danazol

danazol

danazol

danazol

hereditary angioedema

hereditary angioedema

Menstrual abnormalities

weight gain

muscle cramps

myalgias

danazol

weight gain

danazol

weight gain

danazol

weight gain

danazol

weight gain

danazol

weight gain

danazol

muscle cramps

danazol

muscle cramps

danazol

muscle cramps

danazol

muscle cramps

danazol

muscle cramps

danazol

Menstrual abnormalities

danazol

Menstrual abnormalities

danazol

Menstrual abnormalities

danazol

Menstrual abnormalities

danazol

Menstrual abnormalities


Input: Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns. Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad - spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty - nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12 - h intervals over a 3 - day period. One burn site was treated with each of four different CHP concentrations, from 0. 25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0. 25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0. 5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.

chlorhexidine diphosphanilate

Chlorhexidine phosphanilate

CHP

CHP

CHP

silver sulphadiazine

AgSD

AgSD

CHP

CHP

AgSD

AgSD

CHP

AgSD

CHP

burns

infection

burn

burn

burn

burns

burn

burn

pain

pain

chlorhexidine diphosphanilate

pain

chlorhexidine diphosphanilate

pain

Chlorhexidine phosphanilate

pain

Chlorhexidine phosphanilate

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain

CHP

pain


Input: Dose - dependent neurotoxicity of high - dose busulfan in children: a clinical and pharmacological study. Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6. 5 years) receiving high - dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p. o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg / kg, then 600 mg / m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg / kg). Ninety - six patients were not given anticonvulsive prophylaxis; 7 (7. 5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg / kg (1 of 57, 1. 7%) and patients under 600 mg / m2 (6 of 39, 15. 4%) (P less than 0. 02). Twenty - seven patients were given a 600 - mg / m2 busulfan total dose with continuous i. v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic - mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg / m2 busulfan with clonazepam: busulfan cerebrospinal fluid: plasma ratio was 1. 39. This was significantly different (P less than 0. 02) from the cerebrospinal fluid: plasma ratio previously defined in children receiving a 16 - mg / kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose - dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16 - mg / kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.

neurotoxicity

neurotoxic

neurotoxicity

tumors

brain tumors

seizures

neurotoxicity

neurological symptoms

central nervous system disease

neurotoxicity

neurotoxicity

neurotoxicity

busulfan

Busulfan

busulfan

Busulfan

busulfan

busulfan

busulfan

clonazepam

Busulfan

busulfan

clonazepam

busulfan

busulfan

busulfan

clonazepam

busulfan

busulfan

busulfan

busulfan

seizures

Busulfan

seizures

busulfan

seizures

Busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures

Busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures

busulfan

seizures


Input: Histamine antagonists and d - tubocurarine - induced hypotension in cardiac surgical patients. Hemodynamic effects and histamine release by bolus injection of 0. 35 mg / kg of d - tubocurarine were studied in 24 patients. H1 - and H2 - histamine antagonists or placebo were given before dosing with d - tubocurarine in a randomized double - blind fashion to four groups: group 1 - - placebo; group 2 - - cimetidine, 4 mg / kg, plus placebo; group 3 - - chlorpheniramine, 0. 1 mg / kg, plus placebo; and group 4 - - cimetidine plus chlorpheniramine. Histamine release occurred in most patients, the highest level 2 minutes after d - tubocurarine dosing. Group 1 had a moderate negative correlation between plasma histamine change and systemic vascular resistance (r = 0. 58; P less than 0. 05) not present in group 4. Prior dosing with antagonists partially prevented the fall in systemic vascular resistance. These data demonstrate that the hemodynamic changes associated with d - tubocurarine dosing are only partially explained by histamine release. Thus prior dosing with H1 - and H2 - antagonists provides only partial protection.

Histamine

d - tubocurarine

histamine

d - tubocurarine

histamine

d - tubocurarine

cimetidine

chlorpheniramine

cimetidine

chlorpheniramine

Histamine

d - tubocurarine

histamine

d - tubocurarine

histamine

hypotension

d - tubocurarine

hypotension

d - tubocurarine

hypotension

d - tubocurarine

hypotension

d - tubocurarine

hypotension

d - tubocurarine

hypotension


Input: Convulsant effect of lindane and regional brain concentration of GABA and dopamine. Lindane (gamma - hexachlorocyclohexane) is an organochlorine insecticide with known neurotoxic effects. Its mechanism of action is not well understood although it has been proposed that lindane acts as a non - competitive antagonist at the gamma - aminobutyric acid (GABA) - A receptor. We studied the effect of lindane (150 mg / kg) on the GABAergic and dopaminergic systems by measuring the concentration of GABA, dopamine and its metabolites in 7 brain areas at the onset of seizures. All animals suffered tonic convulsions at 18. 3 + / - 1. 4 min after lindane administration. The concentration of GABA was only slightly but significantly decreased in the colliculi without modifications in the other areas. The concentration of dopamine was increased in the mesencephalon and that of its metabolite DOPAC was also increased in the mesencephalon and the striatum.

lindane

GABA

dopamine

Lindane

gamma - hexachlorocyclohexane

lindane

gamma - aminobutyric acid

GABA

lindane

GABA

dopamine

lindane

GABA

dopamine

DOPAC

neurotoxic

seizures

convulsions

lindane

seizures

lindane

convulsions

Lindane

seizures

Lindane

convulsions

gamma - hexachlorocyclohexane

seizures

gamma - hexachlorocyclohexane

convulsions

lindane

seizures

lindane

convulsions

lindane

seizures

lindane

convulsions

lindane

seizures

lindane

convulsions


Input: Unusual complications of antithyroid drug therapy: four case reports and review of literature. Two cases of propylthiouracil - associated acute hepatitis, one case of fatal methimazole - associated hepatocellular necrosis and one case of propylthiouracil - associated lupus - like syndrome are described. The literature related to antithyroid drug side effects and the mechanisms for their occurrence are reviewed and the efficacy and complications of thyroidectomy and radioiodine compared to those of antithyroid drugs. It is concluded that in most circumstances 131I is the therapy of choice for hyperthyroidism.

propylthiouracil

methimazole

propylthiouracil

hepatitis

hepatocellular necrosis

lupus - like syndrome

hyperthyroidism

propylthiouracil

lupus - like syndrome

propylthiouracil

lupus - like syndrome

methimazole

hepatocellular necrosis

propylthiouracil

hepatitis

propylthiouracil

hepatitis


Input: Anticonvulsant actions of MK - 801 on the lithium - pilocarpine model of status epilepticus in rats. MK - 801, a noncompetitive N - methyl - D - aspartate (NMDA) receptor antagonist, was tested for anticonvulsant effects in rats using two seizure models, coadministration of lithium and pilocarpine and administration of a high dose of pilocarpine alone. Three major results are reported. First, pretreatment with MK - 801 produced an effective and dose - dependent anticonvulsant action with the lithium - pilocarpine model but not with rats treated with pilocarpine alone, suggesting that different biochemical mechanisms control seizures in these two models. Second, the anticonvulsant effect of MK - 801 in the lithium - pilocarpine model only occurred after initial periods of seizure activity. This observation is suggested to be an in vivo demonstration of the conclusion derived from in vitro experiments that MK - 801 binding requires agonist - induced opening of the channel sites of the NMDA receptor. Third, although it is relatively easy to block seizures induced by lithium and pilocarpine by administration of anticonvulsants prior to pilocarpine, it is more difficult to terminate ongoing status epilepticus and block the lethality of the seizures. Administration of MK - 801 30 or 60 min after pilocarpine, i. e., during status epilepticus, gradually reduced electrical and behavioral seizure activity and greatly enhanced the survival rate. These results suggest that activation of NMDA receptors plays an important role in status epilepticus and brain damage in the lithium - pilocarpine model. This was further supported by results showing that nonconvulsive doses of NMDA and pilocarpine were synergistic, resulting in status epilepticus and subsequent mortality.

MK - 801

lithium

pilocarpine

MK - 801

N - methyl - D - aspartate

NMDA

lithium

pilocarpine

pilocarpine

MK - 801

lithium

pilocarpine

pilocarpine

MK - 801

lithium

pilocarpine

MK - 801

NMDA

lithium

pilocarpine

pilocarpine

MK - 801

pilocarpine

NMDA

lithium

pilocarpine

NMDA

pilocarpine

status epilepticus

seizure

seizures

seizure

seizures

status epilepticus

seizures

status epilepticus

seizure

status epilepticus

brain damage

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus

lithium

status epilepticus


Input: Nifedipine induced bradycardia in a patient with autonomic neuropathy. An 80 year old diabetic male with evidence of peripheral and autonomic neuropathy was admitted with chest pain. He was found to have atrial flutter at a ventricular rate of 70 / min which slowed down to 30 - 40 / min when nifedipine (60 mg) in 3 divided doses, during which he was paced at a rate of 70 / min. This is inconsistent with the well - established finding that nifedipine induces tachycardia in normally innervated hearts. However, in hearts deprived of compensatory sympathetic drive, it may lead to bradycardia.

Nifedipine

nifedipine

nifedipine

bradycardia

autonomic neuropathy

diabetic

peripheral and autonomic neuropathy

peripheral and autonomic neuropathy

autonomic neuropathy

chest pain

atrial flutter

tachycardia

bradycardia

Nifedipine

tachycardia

nifedipine

tachycardia

nifedipine

tachycardia

Nifedipine

bradycardia

Nifedipine

bradycardia

nifedipine

bradycardia

nifedipine

bradycardia

nifedipine

bradycardia

nifedipine

bradycardia


Input: The effect of haloperidol in cocaine and amphetamine intoxication. The effectiveness of haloperidol pretreatment in preventing the toxic effects of high doses of amphetamine and cocaine was studied in rats. In this model, toxic effects were induced by intraperitoneal (i. p.) injection of amphetamine 75 mg / kg (100% death rate) or cocaine 70 mg / kg (82% death rate). Haloperidol failed to prevent amphetamine - induced seizures, but did lower the mortality rate at most doses tested. Haloperidol decreased the incidence of cocaine - induced seizures at the two highest doses, but the lowering of the mortality rate did not reach statistical significance at any dose. These data suggest a protective role for the central dopamine blocker haloperidol against death from high - dose amphetamine exposure without reducing the incidence of seizures. In contrast, haloperidol demonstrated an ability to reduce cocaine - induced seizures without significantly reducing mortality.

haloperidol

cocaine

amphetamine

haloperidol

amphetamine

cocaine

amphetamine

cocaine

Haloperidol

amphetamine

Haloperidol

cocaine

dopamine

haloperidol

amphetamine

haloperidol

cocaine

seizures

seizures

seizures

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

cocaine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures

amphetamine

seizures


Input: Autoradiographic evidence of estrogen binding sites in nuclei of diethylstilbesterol induced hamster renal carcinomas. Estrogen binding sites were demonstrated by autoradiography in one transplantable and five primary diethylstilbesterol induced renal carcinomas in three hamsters. Radiolabelling, following the in vivo injection of 3H - 17 beta estradiol, was increased only over the nuclei of tumor cells; stereologic analysis revealed a 4. 5 - to 6. 7 - times higher concentration of reduced silver grains over nuclei than cytoplasm of these cells. Despite rapid tubular excretion of estradiol which peaked in less than 1 h, the normal cells did not appear to bind the ligand. This is the first published report documenting the preferential in vivo binding of estrogen to nuclei of cells in estrogen induced hamster renal carcinomas.

estrogen

diethylstilbesterol

Estrogen

diethylstilbesterol

estradiol

silver

estradiol

estrogen

estrogen

renal carcinomas

renal carcinomas

tumor

renal carcinomas

diethylstilbesterol

renal carcinomas

diethylstilbesterol

renal carcinomas

diethylstilbesterol

renal carcinomas

diethylstilbesterol

renal carcinomas

diethylstilbesterol

renal carcinomas

diethylstilbesterol

renal carcinomas


Input: Bradycardia due to biperiden. In a 38 - year - old male patient suffering from a severe postzosteric trigeminal neuralgia, intravenous application of 10 mg biperiden lactate led to a long - lasting paradoxical reaction characterized by considerable bradycardia, dysarthria, and dysphagia. The heart rate was back to normal within 12 hours upon administration of orciprenaline under cardiac monitoring in an intensive care unit. Bradycardia induced by biperiden is attributed to the speed of injection and to a dose - related dual effect of atropine - like drugs on muscarine receptors.

Bradycardia

postzosteric

trigeminal neuralgia

bradycardia

dysarthria

dysphagia

Bradycardia

biperiden

biperiden lactate

orciprenaline

biperiden

atropine

muscarine

biperiden

Bradycardia

biperiden

bradycardia

biperiden

Bradycardia

biperiden

Bradycardia

biperiden

bradycardia

biperiden

Bradycardia

biperiden

dysphagia

biperiden

dysphagia

biperiden

dysarthria

biperiden

dysarthria


Input: Deliberate hypotension induced by labetalol with halothane, enflurane or isoflurane for middle - ear surgery. The feasibility of using labetalol, an alpha - and beta - adrenergic blocking agent, as a hypotensive agent in combination with inhalation anaesthetics (halothane, enflurane or isoflurane) was studied in 23 adult patients undergoing middle - ear surgery. The mean arterial pressure was decreased from 86 + / - 5 (s. e. mean) mmHg to 52 + / - 1 mmHg (11. 5 + / - 0. 7 to 6. 9 + / - 0. 1 kPa) for 98 + / - 10 min in the halothane (H) group, from 79 + / - 5 to 53 + / - 1 mmHg (10. 5 + / - 0. 7 to 7. 1 + / - 0. 1 kPa) for 129 + / - 11 min in the enflurane (E) group, and from 80 + / - 4 to 49 + / - 1 mmHg (10. 7 + / - 0. 5 to 6. 5 + / - 0. 1 kPa) for 135 + / - 15 min in the isoflurane (I) group. The mean H concentration during hypotension in the inspiratory gas was 0. 7 + / - 0. 1 vol%, the mean E concentration 1. 6 + / - 0. 2 vol%, and the mean I concentration 1. 0 + / - 0. 1 vol%. In addition, the patients received fentanyl and d - tubocurarine. The initial dose of labetalol for lowering blood pressure was similar, 0. 52 - 0. 59 mg / kg, in all the groups. During hypotension, the heart rate was stable without tachy - or bradycardia. The operating conditions regarding bleeding were estimated in a double - blind manner, and did not differ significantly between the groups. During hypotension, the serum creatinine concentration rose significantly in all groups from the values before hypotension and returned postoperatively to the initial level in the other groups, except the isoflurane group. After hypotension there was no rebound phenomenon in either blood pressure or heart rate. These results indicate that labetalol induces easily adjustable hypotension without compensatory tachycardia and rebound hypertension.

hypotension

hypotensive

hypotension

hypotension

tachy - or bradycardia

bleeding

hypotension

hypotension

hypotension

hypotension

tachycardia

hypertension

labetalol

halothane

enflurane

isoflurane

labetalol

halothane

enflurane

isoflurane

halothane

H

enflurane

E

isoflurane

I

H

E

I

fentanyl

d - tubocurarine

labetalol

creatinine

isoflurane

labetalol

enflurane

hypotension

enflurane

hypotensive

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotensive

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotensive

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

enflurane

hypotension

E

hypotension

E

hypotensive

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotensive

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotension

E

hypotension

isoflurane

hypotension

isoflurane

hypotensive

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotensive

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotensive

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

I

hypotension

I

hypotensive

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotensive

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotension

I

hypotension

isoflurane

hypotension

isoflurane

hypotensive

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

isoflurane

hypotension

halothane

hypotension

halothane

hypotensive

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotensive

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotensive

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

halothane

hypotension

H

hypotension

H

hypotensive

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotensive

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotension

H

hypotension

labetalol

hypotension

labetalol

hypotensive

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotensive

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotensive

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotensive

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension

labetalol

hypotension


Input: Convulsion following intravenous fluorescein angiography. Tonic - clonic seizures followed intravenous fluorescein injection for fundus angiography in a 47 - year - old male. Despite precautions this adverse reaction recurred on re - exposure to intravenous fluorescein.

Convulsion

Tonic - clonic seizures

fluorescein

fluorescein

fluorescein

fluorescein

Tonic - clonic seizures

fluorescein

Tonic - clonic seizures

fluorescein

Tonic - clonic seizures


Input: Pharmacology of ACC - 9653 (phenytoin prodrug). ACC - 9653, the disodium phosphate ester of 3 - hydroxymethyl - 5, 5 - diphenylhydantoin, is a prodrug of phenytoin with advantageous physicochemical properties. ACC - 9653 is rapidly converted enzymatically to phenytoin in vivo. ACC - 9653 and phenytoin sodium have equivalent anticonvulsant activity against seizures induced by maximal electroshock (MES) in mice following i. p., oral, or i. v. administration. The ED50 doses were 16 mg / kg for i. v. ACC - 9653 and 8 mg / kg for i. v. phenytoin sodium. ACC - 9653 and phenytoin sodium have similar antiarrhythmic activity against ouabain - induced ventricular tachycardia in anesthetized dogs. The total doses of ACC - 9653 or phenytoin sodium necessary to convert the arrhythmia to a normal sinus rhythm were 24 + / - 6 and 14 + / - 3 mg / kg, respectively. Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin - induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC - 9653 (31 mg / kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg / kg). The ACC - 9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP / dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC - 9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i. v., i. m., and i. p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC - 9653 was markedly less than phenytoin sodium following i. m. administration. (ABSTRACT TRUNCATED AT 250 WORDS)

ACC - 9653

phenytoin

ACC - 9653

disodium phosphate ester

3 - hydroxymethyl - 5, 5 - diphenylhydantoin

phenytoin

ACC - 9653

phenytoin

ACC - 9653

phenytoin sodium

ACC - 9653

phenytoin sodium

ACC - 9653

phenytoin sodium

ouabain

ACC - 9653

phenytoin sodium

phenytoin sodium

strophanthidin

ACC - 9653

phenytoin sodium

ACC - 9653

phenytoin sodium

phenytoin sodium

ACC - 9653

phenytoin sodium

ACC - 9653

phenytoin sodium

seizures

ventricular tachycardia

arrhythmia

arrhythmias

toxicity

ouabain

ventricular tachycardia

strophanthidin

arrhythmia

strophanthidin

arrhythmias


Input: Phenytoin induced fatal hepatic injury. A 61 year old female developed fatal hepatic failure after phenytoin administration. A typical multisystem clinical pattern precedes the manifestations of hepatic injury. The hematologic, biochemical and pathologic features indicate a mixed hepatocellular damage due to drug hypersensitivity. In a patient receiving phenytoin who presents a viral - like illness, early recognition and discontinuation of the drug are mandatory.

Phenytoin

phenytoin

phenytoin

hepatic injury

hepatic failure

hepatic injury

hepatocellular damage

drug hypersensitivity

Phenytoin

hepatic failure

phenytoin

hepatic failure

phenytoin

hepatic failure

Phenytoin

drug hypersensitivity

phenytoin

drug hypersensitivity

phenytoin

drug hypersensitivity


Input: Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists. We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day + 7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day + 7 (p less than 0. 001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization - induced encephalopathy in mice.

pertussis vaccine

histamine

cyproheptadine

mianserin

chlorpheniramine

histamine

pertussis

pertussis

pertussis

encephalopathy

pertussis vaccine

encephalopathy


Input: Support for adrenaline - hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion. In a double blind, crossover study 6 h infusions of adrenaline (15 ng / kg / min; 1 ng = 5. 458 pmol), noradrenaline (30 ng / kg / min; 1 ng = 5. 911 pmol), and a 5% dextrose solution (5. 4 ml / h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra - arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0. 001). Thus, " stress " levels of adrenaline (230 pg / ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline - hypertension hypothesis in man.

adrenaline

adrenaline

adrenaline

noradrenaline

dextrose

Adrenaline

noradrenaline

dextrose

adrenaline

adrenaline

hypertension

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

Adrenaline

hypertension

Adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension

adrenaline

hypertension


Input: Effect of alkylxanthines on gentamicin - induced acute renal failure in the rat. Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8 - phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg - 1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H] inulin and [14C] p - aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin - induced ARF.

alkylxanthines

gentamicin

Adenosine

alkylxanthines

adenosine

8 - phenyltheophylline

theophylline

enprofylline

gentamicin

urea

creatinine

p - aminohippuric acid

polyethylene glycol

NaOH

alkylxanthines

adenosine

gentamicin

acute renal failure

ischaemic

nephrotoxic

acute renal failure

ARF

acute renal failure

necrosis

ARF

gentamicin

acute renal failure

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

acute renal failure

gentamicin

ARF

gentamicin

acute renal failure

gentamicin

ARF


Input: Adverse ocular reactions possibly associated with isotretinoin. A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).

isotretinoin

isotretinoin

Isotretinoin

acne

Blepharoconjunctivitis

dry eyes

blurred vision

photodermatitis

papilledema

pseudotumor cerebri

corneal opacities

congenital abnormalities

microphthalmos

hypertelorism

optic nerve hypoplasia

isotretinoin

blurred vision

isotretinoin

blurred vision

Isotretinoin

blurred vision

isotretinoin

corneal opacities

isotretinoin

corneal opacities

Isotretinoin

corneal opacities

isotretinoin

papilledema

isotretinoin

papilledema

Isotretinoin

papilledema

isotretinoin

Blepharoconjunctivitis

isotretinoin

Blepharoconjunctivitis

Isotretinoin

Blepharoconjunctivitis

isotretinoin

pseudotumor cerebri

isotretinoin

pseudotumor cerebri

Isotretinoin

pseudotumor cerebri

isotretinoin

dry eyes

isotretinoin

dry eyes

Isotretinoin

dry eyes

isotretinoin

photodermatitis

isotretinoin

photodermatitis

Isotretinoin

photodermatitis


Input: Procaterol and terbutaline in bronchial asthma. A double - blind, placebo - controlled, cross - over study. Procaterol, a new beta - 2 adrenoceptor stimulant, was studied in a double - blind, placebo - controlled, cross - over trial in patients with bronchial asthma. Oral procaterol 50 micrograms b. d., procaterol 100 micrograms b. d., and terbutaline 5 mg t. i. d., were compared when given randomly in 1 - week treatment periods. The best clinical effect was found with terbutaline. Both anti - asthmatic and tremorgenic effects of procaterol were dose - related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug.

Procaterol

terbutaline

Procaterol

procaterol

procaterol

terbutaline

terbutaline

procaterol

Procaterol

bronchial asthma

bronchial asthma

asthmatic

tremorgenic

Procaterol

tremorgenic

Procaterol

tremorgenic

procaterol

tremorgenic

procaterol

tremorgenic

procaterol

tremorgenic

Procaterol

tremorgenic


Input: Subacute effects of propranolol and B 24 / 76 on isoproterenol - induced rat heart hypertrophy in correlation with blood pressure. We compared the potential beta - receptor blocker, B 24 / 76 i. e. 1 - (2, 4 - dichlorophenoxy) - 3 [2 - 3, 4 - dimethoxyphenyl) ethanolamino] - prop an - 2 - ol, which is characterized by beta 1 - adrenoceptor blocking and beta 2 - adrenoceptor stimulating properties with propranolol. The studies were performed using an experimental model of isoproterenol - induced heart hypertrophy in rats. A correlation of the blood pressure was neither found in the development nor in the attempt to suppress the development of heart hypertrophy with the two beta - receptor blockers. Both beta - blockers influenced the development of hypertrophy to a different, but not reproducible extent. It was possible to suppress the increased ornithine decarboxylase activity with both beta - blockers in hypertrophied hearts, but there was no effect on the heart mass. Neither propranolol nor B 24 / 76 could stop the changes in the characteristic myosin isoenzyme pattern of the hypertrophied rat heart. Thus, the investigations did not provide any evidence that the beta - receptor blockers propranolol and B 24 / 76 have the potency to prevent isoproterenol from producing heart hypertrophy.

propranolol

isoproterenol

propranolol

isoproterenol

ornithine

propranolol

propranolol

isoproterenol

heart hypertrophy

heart hypertrophy

heart hypertrophy

hypertrophy

hypertrophied hearts

hypertrophied

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

hypertrophied hearts

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

hypertrophied hearts

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

heart hypertrophy

isoproterenol

hypertrophied hearts

isoproterenol

heart hypertrophy


Input: Comparison of the effect of oxitropium bromide and of slow - release theophylline on nocturnal asthma. The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow - release theophylline preparation upon nocturnal asthma were compared in a placebo - controlled double - blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t. i. d. (6 subjects) whereas 11 received theophylline at 300 mg b. i. d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage.

oxitropium bromide

theophylline

oxitropium bromide

theophylline

oxitropium

theophylline

oxitropium

oxitropium

theophylline

Oxitropium

theophylline

asthma

asthma

nausea

vomiting

tremors

asthma

theophylline

tremors

theophylline

tremors

theophylline

tremors

theophylline

tremors

theophylline

tremors

theophylline

nausea

theophylline

nausea

theophylline

nausea

theophylline

nausea

theophylline

nausea

theophylline

vomiting

theophylline

vomiting

theophylline

vomiting

theophylline

vomiting

theophylline

vomiting


Input: Penicillin anaphylaxis. A case of oral penicillin anaphylaxis is described, and the terminology, occurrence, clinical manifestations, pathogenesis, prevention, and treatment of anaphylaxis are reviewed. Emergency physicians should be aware of oral penicillin anaphylaxis in order to prevent its occurrence by prescribing the antibiotic judiciously and knowledgeably and to offer optimal medical therapy once this life - threatening reaction has begun.

Penicillin

penicillin

penicillin

anaphylaxis

anaphylaxis

anaphylaxis

anaphylaxis

Penicillin

anaphylaxis

Penicillin

anaphylaxis

Penicillin

anaphylaxis

Penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis

penicillin

anaphylaxis


Input: Reversible valproic acid - induced dementia: a case report. Reversible valproic acid - induced dementia was documented in a 21 - year - old man with epilepsy who had a 3 - year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid - induced hyperammonemia.

valproic acid

valproic acid

valproic acid

valproic acid

dementia

dementia

epilepsy

hyperammonemia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

dementia

valproic acid

hyperammonemia

valproic acid

hyperammonemia

valproic acid

hyperammonemia

valproic acid

hyperammonemia


Input: Reversal of scopolamine - induced amnesia of passive avoidance by pre - and post - training naloxone. In a series of five experiments, the modulating role of naloxone on a scopolamine - induced retention deficit in a passive avoidance paradigm was investigated in mice. Scopolamine, but not methyl scopolamine (1 and 3 mg / kg), induced an amnesia as measured by latency and duration parameters. Naloxone (0. 3, 1, 3, and 10 mg / kg) injected prior to training attenuated the retention deficit with a peak of activity at 3 mg / kg. The effect of naloxone could be antagonized with morphine (1, 3, and 10 mg / kg), demonstrating the opioid specificity of the naloxone effect. Post - training administration of naloxone (3 mg / kg) as a single or as a split dose also attenuated the scopolamine - induced amnesia. Control experiments indicated that neither an increase in pain sensitivity (pre - training naloxone) nor an induced aversive state (post - training naloxone) appear to be responsible for the influence of naloxone on the scopolamine - induced retention deficit. These results extend previous findings implicating a cholinergic - opioid interaction in memory processes. A possible mechanism for this interaction involving the septo - hippocampal cholinergic pathway is discussed.

scopolamine

naloxone

naloxone

scopolamine

Scopolamine

methyl scopolamine

Naloxone

naloxone

morphine

naloxone

naloxone

scopolamine

naloxone

naloxone

naloxone

scopolamine

amnesia

retention deficit

amnesia

retention deficit

amnesia

pain

retention deficit

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

Scopolamine

amnesia

Scopolamine

amnesia

Scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia

scopolamine

amnesia


Input: Electron microscopic investigations of the cyclophosphamide - induced lesions of the urinary bladder of the rat and their prevention by mesna. Fully developed cyclophosphamide - induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location - dependent extent of the damage indicate a direct type of damage which is preceded by a mediator - induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells.

cyclophosphamide

mesna

cyclophosphamide

cyclophosphamide

luminal

mesna

lesions of the urinary bladder

cystitis

edema

necroses

edema

cyclophosphamide

lesions of the urinary bladder

cyclophosphamide

lesions of the urinary bladder

cyclophosphamide

lesions of the urinary bladder


Input: Increase in intragastric pressure during suxamethonium - induced muscle fasciculations in children: inhibition by alfentanil. Changes in intragastric pressure after the administration of suxamethonium 1. 5 mg kg - 1 i. v. were studied in 32 children (mean age 6. 9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg - 1. Anaesthesia was induced with thiopentone 5 mg kg - 1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 + / - 0. 7 (SEM) cm H2O) than in the alfentanil group (7. 7 + / - 1. 5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0. 5 + 4. 78x with r of 0. 78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg - 1 effectively inhibits the incidence and intensity of suxamethonium - induced muscle fasciculations; moreover, intragastric pressure remains at its control value.

suxamethonium

alfentanil

suxamethonium

alfentanil

thiopentone

suxamethonium

alfentanil

alfentanil

suxamethonium

Alfentanil

suxamethonium

muscle fasciculations

muscle fasciculations

muscle fasciculations

muscle fasciculations

muscle fasciculations

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations

suxamethonium

muscle fasciculations


Input: Acute insulin treatment normalizes the resistance to the cardiotoxic effect of isoproterenol in streptozotocin diabetic rats. A morphometric study of isoproterenol induced myocardial fibrosis. The acute effect of insulin treatment on the earlier reported protective effect of streptozotocin diabetes against the cardiotoxic effect of high doses of isoproterenol (ISO) was investigated in rats. Thirty to 135 min after the injection of crystalline insulin, ISO was given subcutaneously and when ISO induced fibrosis in the myocardium was morphometrically analyzed 7 days later, a highly significant correlation (r = 0. 83, 2 p = 0. 006) to the slope of the fall in blood glucose after insulin treatment appeared. The myocardial content of catecholamines was estimated in these 8 day diabetic rats. The norepinephrine content was significantly increased while epinephrine remained unchanged. An enhanced sympathetic nervous system activity with a consequent down regulation of the myocardial beta - adrenergic receptors could, therefore, explain this catecholamine resistance. The rapid reversion after insulin treatment excludes the possibility that streptozotocin in itself causes the ISO resistance and points towards a direct insulin effect on myocardial catecholamine sensitivity in diabetic rats. The phenomenon described might elucidate pathogenetic mechanisms behind toxic myocardial cell degeneration and may possibly have relevance for acute cardiovascular complications in diabetic patients.

cardiotoxic

diabetic

fibrosis

diabetes

cardiotoxic

fibrosis

diabetic

diabetic

diabetic

isoproterenol

streptozotocin

isoproterenol

streptozotocin

isoproterenol

ISO

ISO

ISO

glucose

catecholamines

norepinephrine

epinephrine

catecholamine

streptozotocin

ISO

catecholamine

isoproterenol

fibrosis

isoproterenol

fibrosis

isoproterenol

fibrosis

isoproterenol

fibrosis

isoproterenol

fibrosis

isoproterenol

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

ISO

fibrosis

streptozotocin

diabetic

streptozotocin

diabetes

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetes

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetes

streptozotocin

diabetic

streptozotocin

diabetic

streptozotocin

diabetic


Input: Differential effects of non - steroidal anti - inflammatory drugs on seizures produced by pilocarpine in rats. The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non - steroidal anti - inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg / kg (60 - 174), and phenylbutazone, 59 mg / kg (50 - 70) converted the non - convulsant dose of pilocarpine, 200 mg / kg, to a convulsant one. Indomethacin, 1 - 10 mg / kg, and ibuprofen, 10 - 100 mg / kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22 - 30) mg / kg, prevented seizures and protected rats from seizure - related brain damage induced by pilocarpine, 380 mg / kg. These results indicate that non - steroidal anti - inflammatory drugs differentially modulate the threshold for pilocarpine - induced seizures.

seizures

seizures

status epilepticus

seizures

seizures

seizures

seizure

brain damage

seizures

pilocarpine

pilocarpine

sodium salicylate

phenylbutazone

indomethacin

ibuprofen

mefenamic acid

pilocarpine

sodium salicylate

phenylbutazone

pilocarpine

Indomethacin

ibuprofen

pilocarpine

Mefenamic acid

pilocarpine

pilocarpine

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizure

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizures

phenylbutazone

seizure

phenylbutazone

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizure

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizures

sodium salicylate

seizure

sodium salicylate

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus

pilocarpine

status epilepticus


Input: Acute neurologic dysfunction after high - dose etoposide therapy for malignant glioma. Etoposide (VP - 16 - 213) has been used in the treatment of many solid tumors and hematologic malignancies. When used in high doses and in conjunction with autologous bone marrow transplantation, this agent has activity against several treatment - resistant cancers including malignant glioma. In six of eight patients (75%) who we treated for recurrent or resistant glioma, sudden severe neurologic deterioration occurred. This developed a median of 9 days after initiation of high - dose etoposide therapy. Significant clinical manifestations have included confusion, papilledema, somnolence, exacerbation of motor deficits, and sharp increase in seizure activity. These abnormalities resolved rapidly after initiation of high - dose intravenous dexamethasone therapy. In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high - dose etoposide therapy for malignant glioma.

Acute neurologic dysfunction

malignant glioma

tumors

hematologic malignancies

cancers

malignant glioma

glioma

neurologic deterioration

confusion

papilledema

somnolence

motor deficits

seizure

tumor

edema

toxicity

malignant glioma

etoposide

Etoposide

VP - 16 - 213

etoposide

dexamethasone

etoposide

etoposide

confusion

Etoposide

confusion

VP - 16 - 213

confusion

etoposide

confusion

etoposide

confusion

etoposide

seizure

Etoposide

seizure

VP - 16 - 213

seizure

etoposide

seizure

etoposide

seizure

etoposide

papilledema

Etoposide

papilledema

VP - 16 - 213

papilledema

etoposide

papilledema

etoposide

papilledema


Input: Progressive bile duct injury after thiabendazole administration. A 27 - yr - old man developed jaundice 2 wk after exposure to thiabendazole. Cholestasis persisted for 3 yr, at which time a liver transplant was performed. Two liver biopsy specimens and the hepatectomy specimen were remarkable for almost complete disappearance of interlobular bile ducts. Prominent fibrosis and hepatocellular regeneration were also present; however, the lobular architecture was preserved. This case represents an example of " idiosyncratic " drug - induced liver damage in which the primary target of injury is the bile duct. An autoimmune pathogenesis of the bile duct destruction is suggested.

bile duct injury

jaundice

Cholestasis

fibrosis

drug - induced liver damage

bile duct destruction

thiabendazole

thiabendazole

thiabendazole

drug - induced liver damage

thiabendazole

drug - induced liver damage

thiabendazole

Cholestasis

thiabendazole

Cholestasis


Input: Differential effects of 1, 4 - dihydropyridine calcium channel blockers: therapeutic implications. Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long - term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.

1, 4 - dihydropyridine

calcium channel blockers

calcium

calcium channel blocking agents

calcium channel blockers

verapamil

diltiazem

dihydropyridine

calcium channel blockers

dihydropyridine

nifedipine

calcium channel blockers

nitrendipine

nisoldipine

nisoldipine

nimodipine

dihydropyridine

calcium channel blockers

cardiovascular disease

cardiovascular diseases

angina

hypertension

hypertension

angina

subarachnoid hemorrhage

migraine headache

dementia

stroke

headache

flushing

palpitations

edema

nausea

anorexia

dizziness

calcium channel blockers

anorexia

calcium channel blocking agents

anorexia

calcium channel blockers

anorexia

calcium channel blockers

anorexia

calcium channel blockers

anorexia

calcium channel blockers

anorexia

calcium channel blockers

dizziness

calcium channel blocking agents

dizziness

calcium channel blockers

dizziness

calcium channel blockers

dizziness

calcium channel blockers

dizziness

calcium channel blockers

dizziness

calcium channel blockers

edema

calcium channel blocking agents

edema

calcium channel blockers

edema

calcium channel blockers

edema

calcium channel blockers

edema

calcium channel blockers

edema

calcium channel blockers

headache

calcium channel blocking agents

headache

calcium channel blockers

headache

calcium channel blockers

headache

calcium channel blockers

headache

calcium channel blockers

headache

calcium channel blockers

nausea

calcium channel blocking agents

nausea

calcium channel blockers

nausea

calcium channel blockers

nausea

calcium channel blockers

nausea

calcium channel blockers

nausea

calcium channel blockers

flushing

calcium channel blocking agents

flushing

calcium channel blockers

flushing

calcium channel blockers

flushing

calcium channel blockers

flushing

calcium channel blockers

flushing


Input: The enhancement of aminonucleoside nephrosis by the co - administration of protamine. An experimental model of focal segmental glomerular sclerosis (FSGS) was developed in rats by the combined administration of puromycin - aminonucleoside (AMNS) and protamine sulfate (PS). Male Sprague - Dawley rats, uninephrectomized three weeks before, received daily injections of subcutaneous AMNS (1 mg / 100 g body wt) and intravenous PS (2 separated doses of 2. 5 mg / 100 g body wt) for four days. The series of injections were repeated another three times at 10 day intervals. The animals were sacrificed on days 24, 52, and 80. They developed nephrotic syndrome and finally renal failure. The time - course curve of creatinine clearance dropped and showed significant difference (P less than 0. 01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end - stage renal disease.

aminonucleoside

puromycin - aminonucleoside

AMNS

protamine sulfate

PS

AMNS

PS

creatinine

AMNS

PS

ruthenium

PS

AMNS

nephrosis

focal segmental glomerular sclerosis

FSGS

nephrotic syndrome

renal failure

FSGS

toxicity

FSGS

end - stage renal disease

aminonucleoside

focal segmental glomerular sclerosis

aminonucleoside

FSGS

aminonucleoside

FSGS

aminonucleoside

FSGS

puromycin - aminonucleoside

focal segmental glomerular sclerosis

puromycin - aminonucleoside

FSGS

puromycin - aminonucleoside

FSGS

puromycin - aminonucleoside

FSGS

AMNS

focal segmental glomerular sclerosis

AMNS

FSGS

AMNS

FSGS

AMNS

FSGS

AMNS

focal segmental glomerular sclerosis

AMNS

FSGS

AMNS

FSGS

AMNS

FSGS

AMNS

focal segmental glomerular sclerosis

AMNS

FSGS

AMNS

FSGS

AMNS

FSGS

AMNS

focal segmental glomerular sclerosis

AMNS

FSGS

AMNS

FSGS

AMNS

FSGS

aminonucleoside

nephrotic syndrome

puromycin - aminonucleoside

nephrotic syndrome

AMNS

nephrotic syndrome

AMNS

nephrotic syndrome

AMNS

nephrotic syndrome

AMNS

nephrotic syndrome

aminonucleoside

end - stage renal disease

puromycin - aminonucleoside

end - stage renal disease

AMNS

end - stage renal disease

AMNS

end - stage renal disease

AMNS

end - stage renal disease

AMNS

end - stage renal disease


Input: Theophylline neurotoxicity in pregnant rats. The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague - Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats.

Theophylline

theophylline

aminophylline

Theophylline

Theophylline

theophylline

neurotoxicity

neurotoxicity

seizures

seizures

neurotoxic

aminophylline

seizures

aminophylline

seizures


Input: Hyperkalemia induced by indomethacin and naproxen and reversed by fludrocortisone. We have described a patient with severe rheumatoid arthritis and a history of mefenamic acid nephropathy in whom hyperkalemia and inappropriate hypoaldosteronism were caused by both indomethacin and naproxen, without major decline in renal function. It is likely that preexisting renal disease predisposed this patient to type IV renal tubular acidosis with prostaglandin synthetase inhibitors. Because he was unable to discontinue nonsteroidal anti - inflammatory drug therapy, fludrocortisone was added, correcting the hyperkalemia and allowing indomethacin therapy to be continued safely.

Hyperkalemia

rheumatoid arthritis

nephropathy

hyperkalemia

hypoaldosteronism

renal disease

type IV renal tubular acidosis

hyperkalemia

indomethacin

naproxen

fludrocortisone

mefenamic acid

indomethacin

naproxen

prostaglandin

fludrocortisone

indomethacin

mefenamic acid

nephropathy

mefenamic acid

renal disease

indomethacin

Hyperkalemia

indomethacin

hyperkalemia

indomethacin

hyperkalemia

indomethacin

Hyperkalemia

indomethacin

hyperkalemia

indomethacin

hyperkalemia

indomethacin

Hyperkalemia

indomethacin

hyperkalemia

indomethacin

hyperkalemia

naproxen

hypoaldosteronism

naproxen

type IV renal tubular acidosis

naproxen

hypoaldosteronism

naproxen

type IV renal tubular acidosis

naproxen

Hyperkalemia

naproxen

hyperkalemia

naproxen

hyperkalemia

naproxen

Hyperkalemia

naproxen

hyperkalemia

naproxen

hyperkalemia

indomethacin

hypoaldosteronism

indomethacin

type IV renal tubular acidosis

indomethacin

hypoaldosteronism

indomethacin

type IV renal tubular acidosis

indomethacin

hypoaldosteronism

indomethacin

type IV renal tubular acidosis


Input: Hypotension as a manifestation of cardiotoxicity in three patients receiving cisplatin and 5 - fluorouracil. Cardiac symptoms, including hypotension, developed in three patients with advanced colorectal carcinoma while being treated with cisplatin (CDDP) and 5 - fluorouracil (5 - FU). In two patients, hypotension was associated with severe left ventricular dysfunction. All three patients required therapy discontinuation. Cardiac enzymes remained normal despite transient electrocardiographic (EKG) changes. The presentation and cardiac evaluation (hemodynamic, echocardiographic, and scintigraphic) of these patients suggest new manifestations of 5 - FU cardiotoxicity that may be influenced by CDDP. The possible pathophysiologic mechanisms are discussed.

Hypotension

cardiotoxicity

hypotension

colorectal carcinoma

hypotension

left ventricular dysfunction

cardiotoxicity

cisplatin

5 - fluorouracil

cisplatin

CDDP

5 - fluorouracil

5 - FU

5 - FU

CDDP

5 - fluorouracil

Hypotension

5 - fluorouracil

hypotension

5 - fluorouracil

hypotension

5 - fluorouracil

Hypotension

5 - fluorouracil

hypotension

5 - fluorouracil

hypotension

5 - FU

Hypotension

5 - FU

hypotension

5 - FU

hypotension

5 - FU

Hypotension

5 - FU

hypotension

5 - FU

hypotension

5 - fluorouracil

left ventricular dysfunction

5 - fluorouracil

left ventricular dysfunction

5 - FU

left ventricular dysfunction

5 - FU

left ventricular dysfunction

cisplatin

Hypotension

cisplatin

hypotension

cisplatin

hypotension

cisplatin

Hypotension

cisplatin

hypotension

cisplatin

hypotension

CDDP

Hypotension

CDDP

hypotension

CDDP

hypotension

CDDP

Hypotension

CDDP

hypotension

CDDP

hypotension

cisplatin

left ventricular dysfunction

cisplatin

left ventricular dysfunction

CDDP

left ventricular dysfunction

CDDP

left ventricular dysfunction


Input: Fatal aplastic anemia in a patient treated with carbamazepine. A case of fatal aplastic anemia due to carbamazepine treatment in an epileptic woman is reported. Despite concerns of fatal bone marrow toxicity due to carbamazepine, this is only the fourth documented and published report. Carbamazepine is a safe drug, but physicians and patients should be aware of the exceedingly rare but potentially fatal side effects, better prevented by clinical than by laboratory monitoring.

aplastic anemia

aplastic anemia

epileptic

bone marrow toxicity

carbamazepine

carbamazepine

carbamazepine

Carbamazepine

carbamazepine

aplastic anemia

carbamazepine

aplastic anemia

carbamazepine

aplastic anemia

carbamazepine

aplastic anemia

carbamazepine

aplastic anemia

carbamazepine

aplastic anemia

Carbamazepine

aplastic anemia

Carbamazepine

aplastic anemia