Input: Participation of a bulbospinal serotonergic pathway in the rat brain in clonidine - induced hypotension and bradycardia. The effects of microinjection of clonidine (1 - 10 micrograms in 1 microliter) into a region adjacent to the ventrolateral surface of the medulla oblongata on cardiovascular function were assessed in urethane - anesthetized rats. Intramedullary administration of clonidine, but not saline vehicle, caused a dose - dependent decrease in both the mean arterial pressure and the heart rate. The clonidine - induced hypotension was antagonized by prior spinal transection, but not bilateral vagotomy. On the other hand, the clonidine - induced bradycardia was antagonized by prior bilateral vagotomy, but not spinal transection. Furthermore, selective destruction of the spinal 5 - HT nerves, produced by bilateral spinal injection of 5, 7 - dihydroxytryptamine, reduced the magnitude of the vasodepressor or the bradycardiac responses to clonidine microinjected into the area near the ventrolateral surface of the medulla oblongata in rats. The data indicate that a bulbospinal serotonergic pathway is involved in development of clonidine - induced hypotension and bradycardia. The induced hypotension is brought about by a decrease in sympathetic efferent activity, whereas the induced bradycardia was due to an increase in vagal efferent activity.

clonidine

clonidine

urethane

clonidine

clonidine

clonidine

5 - HT

5, 7 - dihydroxytryptamine

clonidine

clonidine

hypotension

bradycardia

hypotension

bradycardia

bradycardiac

hypotension

bradycardia

hypotension

bradycardia

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

hypotension

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardia

clonidine

bradycardiac

clonidine

bradycardia

clonidine

bradycardia


Input: Hypertension in neuroblastoma induced by imipramine. Hypertension is a well - known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190 / 160) in a 4 - year - old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient' s tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.

Hypertension

neuroblastoma

Hypertension

neuroblastoma

hypertension

neuroblastoma

behavior disorder

tumor

hypertensive

hypertension

neuroblastoma

imipramine

Imipramine

Imipramine

Imipramine

catecholamines

Imipramine

imipramine

Hypertension

imipramine

Hypertension

imipramine

hypertension

imipramine

hypertensive

imipramine

hypertension

Imipramine

Hypertension

Imipramine

Hypertension

Imipramine

hypertension

Imipramine

hypertensive

Imipramine

hypertension

Imipramine

Hypertension

Imipramine

Hypertension

Imipramine

hypertension

Imipramine

hypertensive

Imipramine

hypertension

Imipramine

Hypertension

Imipramine

Hypertension

Imipramine

hypertension

Imipramine

hypertensive

Imipramine

hypertension

Imipramine

Hypertension

Imipramine

Hypertension

Imipramine

hypertension

Imipramine

hypertensive

Imipramine

hypertension


Input: Rechallenge of patients who developed oral candidiasis or hoarseness with beclomethasone dipropionate. Of 158 asthmatic patients who were placed on inhaled beclomethasone, 15 (9. 5%) developed either hoarseness (8), oral thrush (6), or both (1). When their adverse reactions subsided, seven of these 15 patients were rechallenged with inhaled beclomethasone. These included five cases who developed hoarseness and three who developed Candidiasis. One patient had both. Oral thrush did not recur, but 60% (3 / 5) of patients with hoarseness had recurrence. We conclude that patients may be restarted on inhaled beclomethasone when clinically indicated; however, because of the high recurrence rate, patients who develop hoarseness should not be re - challenged. Concomitant use of oral prednisone and topical beclomethasone may increase the risk of developing hoarseness or candidiasis.

oral candidiasis

hoarseness

asthmatic

hoarseness

thrush

hoarseness

Candidiasis

thrush

hoarseness

hoarseness

hoarseness

candidiasis

beclomethasone dipropionate

beclomethasone

beclomethasone

beclomethasone

prednisone

beclomethasone

beclomethasone dipropionate

oral candidiasis

beclomethasone dipropionate

thrush

beclomethasone dipropionate

thrush

beclomethasone

oral candidiasis

beclomethasone

thrush

beclomethasone

thrush

beclomethasone

oral candidiasis

beclomethasone

thrush

beclomethasone

thrush

beclomethasone

oral candidiasis

beclomethasone

thrush

beclomethasone

thrush

beclomethasone

oral candidiasis

beclomethasone

thrush

beclomethasone

thrush

beclomethasone dipropionate

hoarseness

beclomethasone dipropionate

hoarseness

beclomethasone dipropionate

hoarseness

beclomethasone dipropionate

hoarseness

beclomethasone dipropionate

hoarseness

beclomethasone dipropionate

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness

beclomethasone

hoarseness


Input: Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient' s weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg / kg / d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott - Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1. 55 g / m2 / d; Group 2, CYA greater than 1. 55 g / m2 / d. Cardiotoxicity that was thought to be related to CYA occurred in 1 / 32 (3%) of patients in Group 1 and in 13 / 52 (25%) patients in Group 2 (P less than 0. 025). Congestive heart failure caused or contributed to death in 0 / 32 patients in Group 1 v 6 / 52 (12%) of patients in Group 2 (P less than 0. 25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0. 5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1. 55 g / m2 / d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.

Cyclophosphamide

cyclophosphamide

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

CYA

cardiotoxicity

cardiotoxicity

cardiotoxicity

toxicity

cardiotoxicity

aplastic anemia

Wiskott - Aldrich syndrome

severe combined immunodeficiency syndrome

cardiotoxicity

congestive heart failure

Cardiotoxicity

Congestive heart failure

cardiotoxicity

aplastic anemia

immunodeficiencies

cardiotoxicity

toxicity

Cyclophosphamide

congestive heart failure

Cyclophosphamide

Congestive heart failure

cyclophosphamide

congestive heart failure

cyclophosphamide

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure

CYA

congestive heart failure

CYA

Congestive heart failure


Input: Studies of risk factors for aminoglycoside nephrotoxicity. The epidemiology of aminoglycoside - induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside - induced nephrotoxicity.

aminoglycoside

aminoglycoside

aminoglycosides

aminoglycosides

aminoglycoside

creatinine

aminoglycoside

nephrotoxicity

nephrotoxicity

glomerular or tubular dysfunction

acute renal failure

liver disease

nephrotoxicity

acute renal failure

shock

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

glomerular or tubular dysfunction

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

glomerular or tubular dysfunction

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycosides

glomerular or tubular dysfunction

aminoglycosides

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycosides

glomerular or tubular dysfunction

aminoglycosides

nephrotoxicity

aminoglycosides

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

glomerular or tubular dysfunction

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity

aminoglycoside

glomerular or tubular dysfunction

aminoglycoside

nephrotoxicity

aminoglycoside

nephrotoxicity


Input: Flurothyl seizure thresholds in mice treated neonatally with a single injection of monosodium glutamate (MSG): evaluation of experimental parameters in flurothyl seizure testing. Monosodium glutamate (MSG) administration to neonatal rodents produces convulsions and results in numerous biochemical and behavioral deficits. These studies were undertaken to determine if neonatal administration of MSG produced permanent alterations in seizure susceptibility, since previous investigations were inconclusive. A flurothyl ether seizure screening technique was used to evaluate seizure susceptibility in adult mice that received neonatal injections of MSG (4 mg / g and 1 mg / g). MSG treatment resulted in significant reductions in whole brain weight but did not alter seizure threshold. A naloxone (5 mg / kg) challenge was also ineffective in altering the seizure thresholds of either control of MSG - treated mice. Flurothyl ether produced hypothermia which was correlated with the duration of flurothyl exposure; however, the relationship of hypothermia to seizure induction was unclear. Flurothyl seizure testing proved to be a rapid and reliable technique with which to evaluate seizure susceptibility.

Flurothyl

monosodium glutamate

MSG

flurothyl

Monosodium glutamate

MSG

MSG

flurothyl

ether

MSG

MSG

naloxone

MSG

Flurothyl

ether

flurothyl

Flurothyl

seizure

seizure

convulsions

seizure

seizure

seizure

seizure

seizure

hypothermia

hypothermia

seizure

seizure

seizure

Flurothyl

hypothermia

Flurothyl

hypothermia

flurothyl

hypothermia

flurothyl

hypothermia

flurothyl

hypothermia

flurothyl

hypothermia

Flurothyl

hypothermia

Flurothyl

hypothermia

flurothyl

hypothermia

flurothyl

hypothermia

Flurothyl

hypothermia

Flurothyl

hypothermia


Input: Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma - vinyl - GABA into the substantia nigra. Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma - aminobutyric acid (GABA) - mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA - synthesizing enzyme, L - glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non - convulsant doses of pilocarpine, 100 and 200 mg / kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine - induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure - related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg / kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg / kg. Application of an irreversible inhibitor of GABA transaminase, gamma - vinyl - GABA (D, L - 4 - amino - hex - 5 - enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg / kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma - vinyl - GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg / kg. The results demonstrate that the threshold for pilocarpine - induced seizures in rats is subjected to the regulation of the GABA - mediated synaptic inhibition within the substantia nigra.

seizures

temporal lobe epilepsy

convulsive

seizures

seizures

seizures

status epilepticus

convulsions

seizure

seizures

seizures

brain damage

convulsions

seizures

pilocarpine

isoniazid

gamma - vinyl - GABA

Pilocarpine

gamma - aminobutyric acid

GABA

pilocarpine

isoniazid

GABA

L - glutamic acid

pilocarpine

pilocarpine

pilocarpine

isoniazid

pilocarpine

GABA

gamma - vinyl - GABA

D, L - 4 - amino - hex - 5 - enoic acid

pilocarpine

gamma - vinyl - GABA

pilocarpine

pilocarpine

GABA

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

Pilocarpine

seizures

Pilocarpine

convulsive

Pilocarpine

seizures

Pilocarpine

seizures

Pilocarpine

seizures

Pilocarpine

convulsions

Pilocarpine

seizure

Pilocarpine

seizures

Pilocarpine

seizures

Pilocarpine

convulsions

Pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsive

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizure

pilocarpine

seizures

pilocarpine

seizures

pilocarpine

convulsions

pilocarpine

seizures


Input: Non - invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion. Electrocardiographic changes after dipyridamole infusion (0. 568 mg / kg / 4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non - MI group), 14 with anterior infarction (ANT - MI) and eight with inferior infarction (INF - MI). Eighty - seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST - segment depression (0. 05 mV or more) was observed in 84% of the non - MI group, 29% of the ANT - MI group, 63% of the INF - MI group and 61% of the total population. Exercise - induced ST depression was observed in 84% of the non - MI group, 43% of the ANT - MI group, 38% of the INF - MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole - induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.

coronary artery disease

coronary artery disease

myocardial infarction

MI

anterior infarction

ANT - MI

inferior infarction

INF - MI

ischemic

depression

MI

ANT - MI

INF - MI

depression

MI

ANT - MI

INF - MI

depression

myocardial ischemia

coronary artery disease

dipyridamole

dipyridamole

dipyridamole

dipyridamole

dipyridamole

dipyridamole

dipyridamole

myocardial ischemia

dipyridamole

myocardial ischemia

dipyridamole

myocardial ischemia

dipyridamole

myocardial ischemia

dipyridamole

myocardial ischemia

dipyridamole

myocardial ischemia


Input: Bradycardia after high - dose intravenous methylprednisolone therapy. In 5 consecutive patients with rheumatoid arthritis who received intravenous high - dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high - dose MP is recommended. High - dose MP may be contraindicated in patients with known heart disease.

Bradycardia

rheumatoid arthritis

bradycardia

sinus bradycardia

heart disease

methylprednisolone

methylprednisolone

MP

MP

MP

methylprednisolone

Bradycardia

methylprednisolone

bradycardia

methylprednisolone

Bradycardia

methylprednisolone

bradycardia

MP

Bradycardia

MP

bradycardia

MP

Bradycardia

MP

bradycardia

MP

Bradycardia

MP

bradycardia


Input: Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine. Downbeat nystagmus is often associated with structural lesions at the craniocervical junction, but has occasionally been reported as a manifestation of metabolic imbalance or drug intoxication. We recorded the eye movements of two patients with reversible downbeat nystagmus related to carbamazepine therapy. The nystagmus of both patients resolved after reduction of the serum carbamazepine levels. Neuroradiologic investigations including magnetic resonance imaging scans in both patients showed no evidence of intracranial abnormality. In patients with downbeat nystagmus who are taking anticonvulsant medications, consideration should be given to reduction in dose before further investigation is undertaken.

downbeat nystagmus

oscillopsia

Downbeat nystagmus

downbeat nystagmus

nystagmus

downbeat nystagmus

carbamazepine

carbamazepine

carbamazepine

carbamazepine

oscillopsia

carbamazepine

oscillopsia

carbamazepine

oscillopsia


Input: Improvement by denopamine (TA - 064) of pentobarbital - induced cardiac failure in the dog heart - lung preparation. The efficacy of denopamine, an orally active beta 1 - adrenoceptor agonist, in improving cardiac failure was assessed in dog heart - lung preparations. Cardiac functions depressed by pentobarbital (118 + / - 28 mg; mean value + / - SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP / dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10 - 300 micrograms) in a dose - dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.

denopamine

TA - 064

pentobarbital

denopamine

pentobarbital

denopamine

denopamine

denopamine

denopamine

cardiac failure

cardiac failure

arrhythmias

cardiac failure

pentobarbital

cardiac failure

pentobarbital

cardiac failure

pentobarbital

cardiac failure

pentobarbital

cardiac failure

pentobarbital

cardiac failure

pentobarbital

cardiac failure


Input: Clonazepam monotherapy for epilepsy in childhood. Sixty patients (age - range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0. 086 + / - 0. 021 mg / kg / day in infants and 0. 057 + / - 0. 022 mg / kg / day in schoolchildren, this difference was statistically significant (p less than 0. 005). The incidence of side effects such as drowsiness and ataxia was only 5%.

Clonazepam

clonazepam

epilepsy

epilepsy

infantile spasms

seizures

seizures

Seizures

seizures

seizures

drowsiness

ataxia

Clonazepam

drowsiness

clonazepam

drowsiness

Clonazepam

ataxia

clonazepam

ataxia


Input: Postmarketing study of timolol - hydrochlorothiazide antihypertensive therapy. A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed - ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9, 037 patients were collected by 1, 455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol - hydrochlorothiazide therapy (P less than 0. 01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1, 453 patients experienced a total of 2, 658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events.

timolol

hydrochlorothiazide

timolol maleate

hydrochlorothiazide

timolol

hydrochlorothiazide

hypertensive

hypertension

fatigue

dizziness

weakness

timolol

fatigue

timolol maleate

fatigue

timolol

fatigue

timolol

dizziness

timolol maleate

dizziness

timolol

dizziness

hydrochlorothiazide

fatigue

hydrochlorothiazide

fatigue

hydrochlorothiazide

fatigue

hydrochlorothiazide

dizziness

hydrochlorothiazide

dizziness

hydrochlorothiazide

dizziness

hydrochlorothiazide

weakness

hydrochlorothiazide

weakness

hydrochlorothiazide

weakness

timolol

weakness

timolol maleate

weakness

timolol

weakness


Input: Salicylate nephropathy in the Gunn rat: potential role of prostaglandins. We examined the potential role of prostaglandins in the development of analgesic nephropathy in the Gunn strain of rat. The homozygous Gunn rats have unconjugated hyperbilirubinemia due to the absence of glucuronyl transferase, leading to marked bilirubin deposition in renal medulla and papilla. These rats are also highly susceptible to develop papillary necrosis with analgesic administration. We used homozygous (jj) and phenotypically normal heterozygous (jJ) animals. Four groups of rats (n = 7) were studied: jj and jJ rats treated either with aspirin 300 mg / kg every other day or sham - treated. After one week, slices of cortex, outer and inner medulla from one kidney were incubated in buffer and prostaglandin synthesis was determined by radioimmunoassay. The other kidney was examined histologically. A marked corticomedullary gradient of prostaglandin synthesis was observed in all groups. PGE2 synthesis was significantly higher in outer medulla, but not cortex or inner medulla, of jj (38 + / - 6 ng / mg prot) than jJ rats (15 + / - 3) (p less than 0. 01). Aspirin treatment reduced PGE2 synthesis in all regions, but outer medullary PGE2 remained higher in jj (18 + / - 3) than jJ rats (9 + / - 2) (p less than 0. 05). PGF2 alpha was also significantly higher in the outer medulla of jj rats with and without aspirin administration (p less than 0. 05). The changes in renal prostaglandin synthesis were accompanied by evidence of renal damage in aspirin - treated jj but not jJ rats as evidenced by: increased incidence and severity of hematuria (p less than 0. 01); increased serum creatinine (p less than 0. 05); and increase in outer medullary histopathologic lesions (p less than 0. 005 compared to either sham - treated jj or aspirin - treated jJ). These results suggest that enhanced prostaglandin synthesis contributes to maintenance of renal function and morphological integrity, and that inhibition of prostaglandin synthesis may lead to pathological renal medullary lesions and deterioration of renal function.

Salicylate

prostaglandins

prostaglandins

glucuronyl

bilirubin

aspirin

prostaglandin

prostaglandin

Aspirin

PGF2 alpha

aspirin

prostaglandin

aspirin

creatinine

aspirin

prostaglandin

prostaglandin

nephropathy

nephropathy

hyperbilirubinemia

papillary necrosis

renal damage

hematuria

pathological renal medullary lesions

deterioration of renal function

aspirin

nephropathy

aspirin

nephropathy

aspirin

renal damage

aspirin

deterioration of renal function

Aspirin

nephropathy

Aspirin

nephropathy

Aspirin

renal damage

Aspirin

deterioration of renal function

aspirin

nephropathy

aspirin

nephropathy

aspirin

renal damage

aspirin

deterioration of renal function

aspirin

nephropathy

aspirin

nephropathy

aspirin

renal damage

aspirin

deterioration of renal function

aspirin

nephropathy

aspirin

nephropathy

aspirin

renal damage

aspirin

deterioration of renal function


Input: Prophylactic lidocaine in the early phase of suspected myocardial infarction. Four hundred two patients with suspected myocardial infarction seen within 6 hours of the onset of symptoms entered a double - blind randomized trial of lidocaine vs placebo. During the 1 hour after administration of the drug the incidence of ventricular fibrillation or sustained ventricular tachycardia among the 204 patients with acute myocardial infarction was low, 1. 5%. Lidocaine, given in a 300 mg dose intramuscularly followed by 100 mg intravenously, did not prevent sustained ventricular tachycardia, although there was a significant reduction in the number of patients with warning arrhythmias between 15 and 45 minutes after the administration of lidocaine (p less than 0. 05). The average plasma lidocaine level 10 minutes after administration for patients without a myocardial infarction was significantly higher than that for patients with an acute infarction. The mean plasma lidocaine level of patients on beta - blocking agents was no different from that in patients not on beta blocking agents. During the 1 - hour study period, the incidence of central nervous system side effects was significantly greater in the lidocaine group, hypotension occurred in 11 patients, nine of whom had received lidocaine, and four patients died from asystole, three of whom had had lidocaine. We cannot advocate the administration of lidocaine prophylactically in the early hours of suspected myocardial infarction.

lidocaine

lidocaine

Lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

lidocaine

myocardial infarction

myocardial infarction

ventricular fibrillation

ventricular tachycardia

myocardial infarction

ventricular tachycardia

arrhythmias

myocardial infarction

infarction

hypotension

asystole

myocardial infarction

lidocaine

hypotension

lidocaine

hypotension

Lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension

lidocaine

hypotension


Input: Evidence for a cholinergic role in haloperidol - induced catalepsy. Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic - induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol - induced catalepsy. Intracranial injection of an acetylcholine - synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems.

haloperidol

neuroleptic

pilocarpine

pilocarpine

haloperidol

atropine

haloperidol

acetylcholine

hemicholinium

haloperidol

neuroleptics

haloperidol

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

pilocarpine

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy


Input: Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion. Barium - supplemented Long - Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms / ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium - induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium - exposed rats relative to the corresponding control - fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium - treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium - treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium - exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium - exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life - long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.

Cardiovascular dysfunction

hypersensitivity

hypertension

disturbances within the cardiovascular system

hypersensitivity

metabolic disturbances

hypersensitivity

cardiomyopathic disorder

sodium pentobarbital

barium chloride

Barium

barium

barium

barium

sodium pentobarbital

barbiturate

barium

ketamine

xylazine

sodium pentobarbital

barium

barium

barium

barium

barium

sodium pentobarbital

barium

barium

barium chloride

cardiomyopathic disorder

barium chloride

hypertension


Input: Propranolol antagonism of phenylpropanolamine - induced hypertension. Phenylpropanolamine (PPA) overdose can cause severe hypertension, intracerebral hemorrhage, and death. We studied the efficacy and safety of propranolol in the treatment of PPA - induced hypertension. Subjects received propranolol either by mouth for 48 hours before PPA or as a rapid intravenous infusion after PPA. PPA, 75 mg alone, increased blood pressure (31 + / - 14 mm Hg systolic, 20 + / - 5 mm Hg diastolic), and propranolol pretreatment antagonized this increase (12 + / - 10 mm Hg systolic, 10 + / - 7 mm Hg diastolic). Intravenous propranolol after PPA also decreased blood pressure. Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62. 5 + / - 20. 9 to 80. 8 + / - 22. 4 ml), the ejection fraction 9% (from 64% + / - 10% to 70% + / - 7%), and cardiac output 14% (from 3. 6 + / - 0. 6 to 4. 1 + / - 1. 0 L / min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 + / - 200 to 2190 + / - 700 dyne X sec / cm5) and was further increased by propranolol 22% (to 2660 + / - 1200 dyne X sec / cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine.

Propranolol

phenylpropanolamine

Phenylpropanolamine

PPA

propranolol

PPA

propranolol

PPA

PPA

PPA

propranolol

propranolol

PPA

PPA

propranolol

PPA

propranolol

PPA

propranolol

PPA

propranolol

PPA

propranolol

norepinephrine

PPA

norepinephrine

hypertension

overdose

hypertension

intracerebral hemorrhage

hypertension

stroke

phenylpropanolamine

hypertension

phenylpropanolamine

hypertension

phenylpropanolamine

hypertension

Phenylpropanolamine

hypertension

Phenylpropanolamine

hypertension

Phenylpropanolamine

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension

PPA

hypertension


Input: Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis. The possible relationship between mesangial dysfunction and development of glomerular sclerosis was studied in the puromycin aminonucleoside (PAN) model. Five male Wistar rats received repeated subcutaneous PAN injections; five controls received saline only. After 4 weeks the PAN rats were severely proteinuric (190 + / - 80 mg / 24 hr), and all rats were given colloidal carbon (CC) intravenously. At 5 months glomerular sclerosis was found in 7. 6 + / - 3. 4% of the glomeruli of PAN rats; glomeruli of the controls were normal. Glomeruli of PAN rats contained significantly more CC than glomeruli of controls. Glomeruli with sclerosis contained significantly more CC than non - sclerotic glomeruli in the same kidneys. CC was preferentially localized within the sclerotic areas of the affected glomeruli. Since mesangial CC clearance from the mesangium did not change during chronic PAN treatment, we conclude that this preferential CC localization within the lesions is caused by an increased CC uptake shortly after injection in apparent vulnerable areas where sclerosis will develop subsequently. Cluster analysis showed a random distribution of lesions in the PAN glomeruli in concordance with the random localization of mesangial areas with dysfunction in this model. Similar to the remnant kidney model in PAN nephrosis the development of glomerular sclerosis may be related to " mesangial overloading. "

glomerular sclerosis

nephrosis

mesangial dysfunction

glomerular sclerosis

proteinuric

glomerular sclerosis

sclerosis

sclerosis

nephrosis

glomerular sclerosis

aminonucleoside

puromycin aminonucleoside

PAN

PAN

PAN

carbon

PAN

PAN

PAN

PAN

PAN

aminonucleoside

proteinuric

puromycin aminonucleoside

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric

PAN

proteinuric


Input: Relationship between nicotine - induced seizures and hippocampal nicotinic receptors. A controversy has existed for several years concerning the physiological relevance of the nicotinic receptor measured by alpha - bungarotoxin binding. Using mice derived from a classical F2 and backcross genetic design, a relationship between nicotine - induced seizures and alpha - bungarotoxin nicotinic receptor concentration was found. Mice sensitive to the convulsant effects of nicotine had greater alpha - bungarotoxin binding in the hippocampus than seizure insensitive mice. The binding sites from seizure sensitive and resistant mice were equally affected by treatment with dithiothreitol, trypsin or heat. Thus it appears that the difference between seizure sensitive and insensitive animals may be due to a difference in hippocampal nicotinic receptor concentration as measured with alpha - bungarotoxin binding.

nicotine

nicotine

nicotine

dithiothreitol

seizures

seizures

seizure

seizure

seizure

nicotine

seizures

nicotine

seizures

nicotine

seizure

nicotine

seizure

nicotine

seizure

nicotine

seizures

nicotine

seizures

nicotine

seizure

nicotine

seizure

nicotine

seizure

nicotine

seizures

nicotine

seizures

nicotine

seizure

nicotine

seizure

nicotine

seizure


Input: The role of p - aminophenol in acetaminophen - induced nephrotoxicity: effect of bis (p - nitrophenyl) phosphate on acetaminophen and p - aminophenol nephrotoxicity and metabolism in Fischer 344 rats. Acetaminophen (APAP) produces proximal tubular necrosis in Fischer 344 (F344) rats. Recently, p - aminophenol (PAP), a known potent nephrotoxicant, was identified as a metabolite of APAP in F344 rats. The purpose of this study was to determine if PAP formation is a requisite step in APAP - induced nephrotoxicity. Therefore, the effect of bis (p - nitrophenyl) phosphate (BNPP), an acylamidase inhibitor, on APAP and PAP nephrotoxicity and metabolism was determined. BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration - dependent manner. Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg / kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg / kg. BNPP did not alter the excretion of APAP or any of its non - deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg / kg. Therefore, the BNPP - induced reduction in APAP - induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP - induced renal tubular necrosis.

p - aminophenol

acetaminophen

bis (p - nitrophenyl) phosphate

acetaminophen

p - aminophenol

Acetaminophen

APAP

p - aminophenol

PAP

APAP

PAP

APAP

bis (p - nitrophenyl) phosphate

BNPP

APAP

PAP

BNPP

APAP

BNPP

APAP

PAP

APAP

PAP

APAP

BNPP

APAP

PAP

APAP

BNPP

APAP

BNPP

PAP

PAP

BNPP

APAP

APAP

PAP

APAP

nephrotoxicity

nephrotoxicity

tubular necrosis

nephrotoxicity

nephrotoxicity

nephrotoxicity

nephrotoxicity

nephrotoxicity

renal tubular necrosis

p - aminophenol

tubular necrosis

p - aminophenol

renal tubular necrosis

p - aminophenol

tubular necrosis

p - aminophenol

renal tubular necrosis

p - aminophenol

tubular necrosis

p - aminophenol

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

PAP

tubular necrosis

PAP

renal tubular necrosis

acetaminophen

tubular necrosis

acetaminophen

renal tubular necrosis

acetaminophen

tubular necrosis

acetaminophen

renal tubular necrosis

Acetaminophen

tubular necrosis

Acetaminophen

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis

APAP

tubular necrosis

APAP

renal tubular necrosis


Input: Morphine - induced seizures in newborn infants. Two neonates suffered from generalized seizures during the course of intravenous morphine sulfate for post - operative analgesia. They received morphine in doses of 32 micrograms / kg / hr and 40 micrograms / kg / hr larger than a group of 10 neonates who received 6 - 24 micrograms / kg / hr and had no seizures. Plasma concentrations of morphine in these neonates was excessive (60 and 90 mg / ml). Other known reasons for seizures were ruled out and the convulsions stopped a few hours after cessation of morphine and did not reoccur in the subsequent 8 months. It is suggested that post - operative intravenous morphine should not exceed 20 micrograms / kg / ml in neonates.

Morphine

morphine sulfate

morphine

morphine

morphine

morphine

seizures

seizures

seizures

seizures

convulsions

Morphine

seizures

Morphine

seizures

Morphine

seizures

Morphine

seizures

Morphine

convulsions

morphine sulfate

seizures

morphine sulfate

seizures

morphine sulfate

seizures

morphine sulfate

seizures

morphine sulfate

convulsions

morphine

seizures

morphine

seizures

morphine

seizures

morphine

seizures

morphine

convulsions

morphine

seizures

morphine

seizures

morphine

seizures

morphine

seizures

morphine

convulsions

morphine

seizures

morphine

seizures

morphine

seizures

morphine

seizures

morphine

convulsions

morphine

seizures

morphine

seizures

morphine

seizures

morphine

seizures

morphine

convulsions


Input: Effect of vincristine sulfate on Pseudomonas infections in monkeys. In rhesus monkeys, intravenous challenge with 0. 6 x 10 (10) to 2. 2 x 10 (10) Pseudomonas aeruginosa organisms caused acute illness of 4 to 5 days' duration with spontaneous recovery in 13 of 15 monkeys; blood cultures became negative 3 to 17 days after challenge. Leukocytosis was observed in all monkeys. Intravenous or intratracheal inoculation of 2. 0 to 2. 5 mg of vincristine sulfate was followed by leukopenia in 4 to 5 days. Intravenous inoculation of 4. 2 x 10 (10) to 7. 8 x 10 (10) pyocin type 6 Pseudomonas organisms in monkeys given vincristine sulfate 4 days previously resulted in fatal infection in 11 of 14 monkeys, whereas none of four receiving Pseudomonas alone died. These studies suggest that an antimetabolite - induced leukopenia predisposes to severe Pseudomonas sepsis and that such monkeys may serve as a biological model for study of comparative efficacy of antimicrobial agents.

vincristine sulfate

vincristine sulfate

vincristine sulfate

Pseudomonas infections

Leukocytosis

leukopenia

infection

leukopenia

sepsis

vincristine sulfate

sepsis

vincristine sulfate

sepsis

vincristine sulfate

sepsis

vincristine sulfate

leukopenia

vincristine sulfate

leukopenia

vincristine sulfate

leukopenia

vincristine sulfate

leukopenia

vincristine sulfate

leukopenia

vincristine sulfate

leukopenia

vincristine sulfate

Pseudomonas infections

vincristine sulfate

Pseudomonas infections

vincristine sulfate

Pseudomonas infections


Input: Central excitatory actions of flurazepam. Toxic actions of flurazepam (FZP) were studied in cats, mice and rats. High doses caused an apparent central excitation, most clearly seen as clonic convulsions, superimposed on general depression. Following a lethal dose, death was always associated with convulsions. Comparing the relative sensitivity to central depression and excitation revealed that rats were least likely to have convulsions at doses that did not first cause loss of consciousness, while cats most clearly showed marked central excitatory actions. Signs of FZP toxocity in cats included excessive salivation, extreme apprehensive behavior, retching, muscle tremors and convulsions. An interaction between FZP and pentylenetetrazol (PTZ) was shown by pretreating mice with FZP before PTZ challenge. As a function of dose, FZP first protected against convulsions and death. At higher doses, however, convulsions again emerged. These doses of FZP were lower than those that would alone cause convulsions. These results may be relevant to the use of FZP in clinical situations in which there is increased neural excitability, such as epilepsy or sedative - hypnotic drug withdrawal.

flurazepam

flurazepam

FZP

FZP

FZP

pentylenetetrazol

PTZ

FZP

PTZ

FZP

FZP

FZP

convulsions

depression

convulsions

depression

convulsions

loss of consciousness

toxocity

salivation

muscle tremors

convulsions

convulsions

convulsions

convulsions

epilepsy

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

flurazepam

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

FZP

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

pentylenetetrazol

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions

PTZ

convulsions


Input: Evidence for cardiac beta 2 - adrenoceptors in man. We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise - and isoproterenol - induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 + / - 4 (SEM) after placebo to 146 + / - 7 bpm after atenolol and 138 + / - 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0. 04 mg / kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1. 8 + / - 0. 3 micrograms after placebo to 38. 9 + / - 8. 3 micrograms after propranolol and 8. 3 + / - 1. 7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2. 3 + / - 0. 3 micrograms) and atenolol (7. 7 + / - 1. 3 micrograms); it was reduced after propranolol (24. 8 + / - 5. 0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11. 7 + / - 2. 1 and 10. 1 + / - 2. 5 ml / ng). These data are consistent with the hypothesis that exercise - induced tachycardia results largely from beta 1 - receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1 - and beta 2 - receptors so that after cardioselective blockade there remains a beta 2 - component that can be blocked with a nonselective drug. While there appear to be beta 2 - receptors in the human heart, their physiologic or pathologic roles remain to be defined.

atenolol

propranolol

isoproterenol

atenolol

propranolol

isoproterenol

atropine

Isoproterenol

propranolol

atenolol

atropine

atenolol

propranolol

atenolol

propranolol

atropine

isoproterenol

tachycardia

tachycardia

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

Isoproterenol

tachycardia

Isoproterenol

tachycardia

Isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia

isoproterenol

tachycardia


Input: Hormones and risk of breast cancer. This paper reports the results of a study of 50 menopausal women receiving hormonal replacement therapy. The majority (29) had surgical menopause; their mean age was 45. 7 years. It was hypothesized that progestins could equilibrate the effects of the estrogenic stimulation on the mammary and endometrial target tissues of women on hormonal replacement therapy. The treatment schedule consisted of conjugated estrogens (Premarin) 1. 25 mg / day for 21 days and Medroxyprogesterone acetate 10 mg / day for 10 days in each month. The mean treatment period was 18 months. During the follow - up period, attention was paid to breast modifications as evidenced by symptomatology, physical examination, and plate thermography. Mastodynia was reported by 21 patients, and physical examination revealed a light increase in breast firmness in 12 women and a moderate increase in breast nodularity in 2 women. Themography confirmed the existence of an excessive breast stimulation in 1 women who complained of moderate mastodynia and in 5 of the 7 women who complained of severe mastodynia. Normalization was obtained by halving the estrogen dose. These results suggest that hormonal replacement therapy can be safely prescribed if the following criteria are satisfied: 1) preliminary evaluation of patients from a clinical, metabolic, cytologic, and mammographic perspective; 2) cyclic treatment schedule, with a progestative phase of 10 days; and 3) periodic complete follow - up, with accurate thermographic evaluation of the breast target tissues.

breast cancer

Mastodynia

mastodynia

mastodynia

progestins

conjugated estrogens

Premarin

Medroxyprogesterone acetate

estrogen

conjugated estrogens

Mastodynia

conjugated estrogens

mastodynia

conjugated estrogens

mastodynia

Premarin

Mastodynia

Premarin

mastodynia

Premarin

mastodynia

Medroxyprogesterone acetate

Mastodynia

Medroxyprogesterone acetate

mastodynia

Medroxyprogesterone acetate

mastodynia


Input: Early infections in kidney, heart, and liver transplant recipients on cyclosporine. Eighty - one renal, seventeen heart, and twenty - four liver transplant patients were followed for infection. Seventeen renal patients received azathioprine (Aza) and prednisone as part of a randomized trial of immunosuppression with 21 cyclosporine - and - prednisone - treated renal transplant patients. All others received cyclosporine and prednisone. The randomized Aza patients had more overall infections (P less than 0. 05) and more nonviral infections (P less than 0. 02) than the randomized cyclosporine patients. Heart and liver patients had more infections than cyclosporine renal patients but fewer infections than the Aza renal patients. There were no infectious deaths in renal transplant patients on cyclosporine or Aza, but infection played a major role in 3 out of 6 cardiac transplant deaths and in 8 out of 9 liver transplant deaths. Renal patients on cyclosporine had the fewest bacteremias. Analysis of site of infection showed a preponderance of abdominal infections in liver patients, intrathoracic infections in heart patients, and urinary tract infections in renal patients. Pulmonary infections were less common in cyclosporine - treated renal patients than in Aza - treated patients (P less than 0. 05). Aza patients had significantly more staphylococcal infections than all other transplant groups (P less than 0. 005), and systemic fungal infections occurred only in the liver transplant group. Cytomegalovirus (CMV) shedding or serological rises in antibody titer, or both occurred in 78% of cyclosporine patients and 76% of Aza patients. Of the cyclosporine patients, 15% had symptoms related to CMV infection. Serological evidence for Epstein Barr Virus infection was found in 20% of 65 cyclosporine patients studied. Three had associated symptoms, and one developed a lymphoma.

infections

infection

infections

infections

infections

infections

infection

bacteremias

infection

abdominal infections

infections

urinary tract infections

infections

staphylococcal infections

fungal infections

CMV infection

Epstein Barr Virus infection

lymphoma

cyclosporine

azathioprine

Aza

prednisone

cyclosporine

prednisone

cyclosporine

prednisone

Aza

cyclosporine

cyclosporine

Aza

cyclosporine

Aza

cyclosporine

cyclosporine

Aza

Aza

cyclosporine

Aza

cyclosporine

cyclosporine

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infections

cyclosporine

infection

cyclosporine

infection

cyclosporine

infections

cyclosporine

infections

azathioprine

infections

azathioprine

infection

azathioprine

infections

azathioprine

infections

azathioprine

infections

azathioprine

infections

azathioprine

infection

azathioprine

infection

azathioprine

infections

azathioprine

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infections

Aza

infections

Aza

infections

Aza

infections

Aza

infection

Aza

infection

Aza

infections

Aza

infections


Input: Structure - activity and dose - effect relationships of the antagonism of picrotoxin - induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice. Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK - 8 - SE) and nonsulphated cholecystokinin octapeptide (CCK - 8 - NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N - and C - terminal fragments revealed that the C - terminal tetrapeptide (CCK - 5 - 8) was the active centre of the CCK octapeptide molecule. The analogues CCK - 8 - SE and CCK - 8 - NS (dose range 0. 2 - 6. 4 mumol / kg) and caerulein dose range 0. 1 - 0. 8 mumol / kg) showed bell - shaped dose - effect curves, with the greatest maximum inhibition for CCK - 8 - NS. The peptide CCK - 5 - 8 had weak anticonvulsant activity in comparison to the octapeptides, 3. 2 mumol / kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin - induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK - 5 - 8 demonstrated that the effectiveness of the beta - alanyl derivatives of CCK - 5 - 8 were enhanced and that they were equipotent with CCK - 8 - SE. Of the CCK - 2 - 8 analogues, Ser (SO3H) 7 - Ac - CCK - 2 - 8 - SE and Thr (SO3H) 7 - Ac - CCK - 2 - 8 - SE and Hyp (SO3H) - Ac - CCK - 2 - 8 - SE were slightly more active than CCK - 8 - SE.

picrotoxin

cholecystokinin

cholecystokinin

cholecystokinin octapeptide

CCK - 8

cholecystokinin octapeptide

CCK - 8

picrotoxin

CCK - 8

CCK - 8

caerulein

CCK - 8

diazepam

picrotoxin

diazepam

CCK - 8

CCK - 8

seizures

seizures

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures

picrotoxin

seizures


Input: Vasopressin as a possible contributor to hypertension. The role of vasopressin as a pressor agent to the hypertensive process was examined. Vasopressin plays a major role in the pathogenesis of DOCA - salt hypertension, since the elevation of blood pressure was not substantial in the rats with lithium - treated diabetes insipidus after DOCA - salt treatment. Administration of DDAVP which has antidiuretic action but minimal vasopressor effect failed to increase blood pressure to the levels observed after administration of AVP. Furthermore, the pressor action of vasopressin appears to be important in the development of this model of hypertension, since the enhanced pressor responsiveness to the hormone was observed in the initial stage of hypertension. Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension.

Vasopressin

vasopressin

Vasopressin

DOCA

lithium

DOCA

DDAVP

vasopressin

vasopressin

vasopressin

angiotensin

sodium

vasopressin

hypertension

hypertensive

hypertension

diabetes insipidus

hypertension

hypertension

hypertension

hypertension

DOCA

hypertension

DOCA

hypertensive

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertensive

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

DOCA

hypertension

lithium

diabetes insipidus


Input: Toxic hepatitis induced by disulfiram in a non - alcoholic. A reversible toxic liver damage was observed in a non - alcoholic woman treated with disulfiram. The causative relationship was proven by challenge.

Toxic hepatitis

toxic liver damage

disulfiram

disulfiram

disulfiram

Toxic hepatitis

disulfiram

toxic liver damage

disulfiram

Toxic hepatitis

disulfiram

toxic liver damage


Input: Atrial thrombosis involving the heart of F - 344 rats ingesting quinacrine hydrochloride. Quinacrine hydrochloride is toxic for the heart of F - 344 rats. Rats treated with 500 ppm quinacrine hydrochloride in the diet all developed a high incidence of left atrial thrombosis. The lesion was associated with cardiac hypertrophy and dilatation and focal myocardial degeneration. Rats died from cardiac hypertrophy with severe acute and chronic congestion of the lungs, liver, and other organs. Seventy percent of rats given 250 ppm quinacrine hydrochloride and 1, 000 ppm sodium nitrite simultaneously in the diet had thrombosis of the atria of the heart, while untreated control rats in this laboratory did not have atrial thrombosis. Sodium nitrite in combination with quinacrine hydrochloride appeared to have no additional effect.

Atrial thrombosis

atrial thrombosis

cardiac hypertrophy

myocardial degeneration

cardiac hypertrophy

thrombosis

atrial thrombosis

quinacrine hydrochloride

Quinacrine hydrochloride

quinacrine hydrochloride

quinacrine hydrochloride

sodium nitrite

Sodium nitrite

quinacrine hydrochloride

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

Quinacrine hydrochloride

cardiac hypertrophy

Quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

cardiac hypertrophy

quinacrine hydrochloride

Atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

Quinacrine hydrochloride

Atrial thrombosis

Quinacrine hydrochloride

atrial thrombosis

Quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

Atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

Atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

Atrial thrombosis

quinacrine hydrochloride

atrial thrombosis

quinacrine hydrochloride

atrial thrombosis


Input: Alternating sinus rhythm and intermittent sinoatrial block induced by propranolol. Alternating sinus rhythm and intermittent sinoatrial (S - A) block was observed in a 57 - year - old woman, under treatment for angina with 80 mg propranolol daily. The electrocardiogram showed alternation of long and short P - P intervals and occasional pauses. These pauses were always preceded by the short P - P intervals and were usually followed by one or two P - P intervals of 0. 92 - 0. 95 s representing the basic sinus cycle. Following these basic sinus cycles, alternating rhythm started with the longer P - P interval. The long P - P intervals ranged between 1. 04 - 1. 12 s and the short P - P intervals between 0. 80 - 0. 84 s, respectively. The duration of the pauses were equal or almost equal to one short plus one long P - P interval or to twice the basic sinus cycle. In one recording a short period of regular sinus rhythm with intermittent 2 / 1 S - A block was observed. This short period of sinus rhythm was interrupted by sudden prolongation of the P - P interval starting the alternative rhythm. There were small changes in the shape of the P waves and P - R intervals. S - A conduction through two pathways, the first with 2 / 1 block the second having 0. 12 - 0. 14 s longer conduction time and with occasional 2 / 1 block was proposed for the explanation of the alternating P - P interval and other electrocardiographic features seen. Atropine 1 mg given intravenously resulted in shortening of all P - P intervals without changing the rhythm. The abnormal rhythm disappeared with the withdrawal of propranolol and when the drug was restarted a 2 / 1 S - A block was seen. This was accepted as evidence for propranolol being the cause of this conduction disorder.

Alternating sinus rhythm

sinoatrial block

Alternating sinus rhythm

sinoatrial (S - A) block

angina

alternating rhythm

S - A block

S - A block

conduction disorder

propranolol

propranolol

Atropine

propranolol

propranolol

propranolol

sinoatrial block

propranolol

sinoatrial (S - A) block

propranolol

S - A block

propranolol

S - A block

propranolol

sinoatrial block

propranolol

sinoatrial (S - A) block

propranolol

S - A block

propranolol

S - A block

propranolol

sinoatrial block

propranolol

sinoatrial (S - A) block

propranolol

S - A block

propranolol

S - A block

propranolol

sinoatrial block

propranolol

sinoatrial (S - A) block

propranolol

S - A block

propranolol

S - A block

propranolol

Alternating sinus rhythm

propranolol

Alternating sinus rhythm

propranolol

alternating rhythm

propranolol

Alternating sinus rhythm

propranolol

Alternating sinus rhythm

propranolol

alternating rhythm

propranolol

Alternating sinus rhythm

propranolol

Alternating sinus rhythm

propranolol

alternating rhythm

propranolol

Alternating sinus rhythm

propranolol

Alternating sinus rhythm

propranolol

alternating rhythm


Input: Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma - bearing LOU / M / WSL rat. Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU / M / WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15. 8 + / - 3. 3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0. 015 - 4. 0 mg / kg body wt). Tumor regression was observed with 0. 5 mg doxorubicin / kg. Complete disappearance of the tumor was induced with 1. 0 mg doxorubicin / kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1. 0 mg doxorubicin / kg. Light microscopic evidence of renal damage was seen above a dose of 0. 5 mg doxorubicin / kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1. 0 mg doxorubicin / kg, the serum albumin level decreased from 33. 6 + / - 4. 1 to 1. 5 + / - 0. 5 g / liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non - tumor - bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU / M / WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.

cardiotoxicity

nephrotoxicity

immunocytoma

cardiotoxicity

nephrotoxicity

immunocytoma

tumor

Tumor

tumor

cardiotoxicity

renal damage

albuminuria

Ascites

hydrothorax

tumor

cardiotoxicity

nephrotoxicity

Albuminuria

renal damage

ascites

hydrothorax

cardiomyopathy

doxorubicin

doxorubicin

doxorubicin

doxorubicin

doxorubicin

doxorubicin

doxorubicin

doxorubicin

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

hydrothorax

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

Ascites

doxorubicin

ascites

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria

doxorubicin

albuminuria

doxorubicin

Albuminuria


Input: Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops. A 69 - yr - old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24 - h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2. 6 ng ml - 1) was consistent with partial beta - adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.

bradycardia

hypotension

bradycardia

hypotensive

bradycardia

hypotension

timolol

pilocarpine

pilocarpine nitrate

timolol maleate

halothane

timolol

pilocarpine

Timolol

pilocarpine

timolol

halothane

Pilocarpine

timolol

hypotension

timolol

hypotensive

timolol

hypotension

timolol maleate

hypotension

timolol maleate

hypotensive

timolol maleate

hypotension

timolol

hypotension

timolol

hypotensive

timolol

hypotension

Timolol

hypotension

Timolol

hypotensive

Timolol

hypotension

timolol

hypotension

timolol

hypotensive

timolol

hypotension

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine nitrate

bradycardia

pilocarpine nitrate

bradycardia

pilocarpine nitrate

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

pilocarpine

bradycardia

Pilocarpine

bradycardia

Pilocarpine

bradycardia

Pilocarpine

bradycardia

pilocarpine

hypotension

pilocarpine

hypotensive

pilocarpine

hypotension

pilocarpine nitrate

hypotension

pilocarpine nitrate

hypotensive

pilocarpine nitrate

hypotension

pilocarpine

hypotension

pilocarpine

hypotensive

pilocarpine

hypotension

pilocarpine

hypotension

pilocarpine

hypotensive

pilocarpine

hypotension

Pilocarpine

hypotension

Pilocarpine

hypotensive

Pilocarpine

hypotension

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol maleate

bradycardia

timolol maleate

bradycardia

timolol maleate

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

Timolol

bradycardia

Timolol

bradycardia

Timolol

bradycardia

timolol

bradycardia

timolol

bradycardia

timolol

bradycardia


Input: Succinylcholine apnoea: attempted reversal with anticholinesterases. Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train - of - four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2. 5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.

Succinylcholine

succinylcholine

Edrophonium

succinylcholine

edrophonium

neostigmine

succinylcholine

succinylcholine

apnoea

neuromuscular blockade

apnoea

Succinylcholine

apnoea

Succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea

succinylcholine

apnoea


Input: Effect of doxorubicin on [omega - I - 131] heptadecanoic acid myocardial scintigraphy and echocardiography in dogs. The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega - I - 131] heptadecanoic acid (I - 131 HA), and on global left - ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin - treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg / kg. A significant increase in the myocardial t1 / 2 of the I - 131 HA was observed only at a higher cumulative dose, 10 mg / kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I - 131 HA are not the initiating factor in doxorubicin cardiotoxicity.

doxorubicin

[omega - I - 131] heptadecanoic acid

doxorubicin

[omega - I - 131] heptadecanoic acid

I - 131 HA

doxorubicin

doxorubicin

I - 131 HA

doxorubicin

I - 131 HA

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity


Input: Hemodynamics and myocardial metabolism under deliberate hypotension. An experimental study in dogs. Coronary blood flow, cardiac work and metabolism were studied in dogs under sodium nitroprusside (SNP) and trimetaphan (TMP) deliberate hypotension (20% and 40% mean pressure decrease from baseline). Regarding the effects of drug - induced hypotension on coronary blood flow, aortic and coronary sinus metabolic data (pH, pO2, pCO2) we could confirm that nitroprusside hypotension could be safely used to 30% mean blood pressure decrease from control, trimetaphan hypotension to 20% mean blood pressure decrease. Cardiac work was significantly reduced during SNP hypotension. Myocardial O2 consumption and O2 availability were directly dependent on the coronary perfusion. Careful invasive monitoring of the blood pressure, blood gases and of the ECG ST - T segment is mandatory.

hypotension

hypotension

hypotension

hypotension

hypotension

hypotension

sodium nitroprusside

SNP

trimetaphan

TMP

nitroprusside

trimetaphan

SNP

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

TMP

hypotension

TMP

hypotension

TMP

hypotension

TMP

hypotension

TMP

hypotension

TMP

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

trimetaphan

hypotension

sodium nitroprusside

hypotension

sodium nitroprusside

hypotension

sodium nitroprusside

hypotension

sodium nitroprusside

hypotension

sodium nitroprusside

hypotension

sodium nitroprusside

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

nitroprusside

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension

SNP

hypotension


Input: Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat. Male rats received the noradrenaline neurotoxin DSP4 (50 mg / kg) 7 days prior to injection of D - amphetamine (10 or 40 mumol / kg i. p.). The hyperactivity induced by D - amphetamine (10 mumol / kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphetamine - induced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the noradrenaline - uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The present results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.

amphetamine

noradrenaline

D - amphetamine

D - amphetamine

amphetamine

amphetamine

noradrenaline

desipramine

amphetamine

hyperactivity

stereotypies

hyperactivity

neurotoxic

D - amphetamine

hyperactivity

D - amphetamine

hyperactivity

D - amphetamine

hyperactivity

D - amphetamine

hyperactivity


Input: Accelerated junctional rhythms during oral verapamil therapy. This study examined the frequency of atrioventricular (AV) dissociation and accelerated junctional rhythms in 59 patients receiving oral verapamil. Accelerated junctional rhythms and AV dissociation were frequent in patients with supraventricular tachyarrhythmias, particularly AV nodal reentry. Verapamil administration to these patients led to an asymptomatic increase in activity of these junctional pacemakers. In patients with various chest pain syndromes, verapamil neither increased the frequency of junctional rhythms nor suppressed their role as escape rhythms under physiologically appropriate circumstances.

Accelerated junctional rhythms

accelerated junctional rhythms

Accelerated junctional rhythms

supraventricular tachyarrhythmias

chest pain

verapamil

verapamil

Verapamil

verapamil

verapamil

Accelerated junctional rhythms

verapamil

accelerated junctional rhythms

verapamil

Accelerated junctional rhythms

verapamil

Accelerated junctional rhythms

verapamil

accelerated junctional rhythms

verapamil

Accelerated junctional rhythms

Verapamil

Accelerated junctional rhythms

Verapamil

accelerated junctional rhythms

Verapamil

Accelerated junctional rhythms

verapamil

Accelerated junctional rhythms

verapamil

accelerated junctional rhythms

verapamil

Accelerated junctional rhythms


Input: Treatment of ovarian cancer with a combination of cis - platinum, adriamycin, cyclophosphamide and hexamethylmelamine. During the last 2 1 / 2 years, 38 patients with ovarian cancer were treated with a combination of cisplatinum (CPDD), 50 mg / m2, adriamycin, 30 mg / m2, cyclophosphamide, 300 mg / m2, on day 1; and hexamethylmelamine (HMM), 6 mg / kg daily, for 14 days. Each course was repeated monthly. 2 patients had stage II, 14 stage III and 22 stage IV disease. 14 of the 38 patients were previously treated with chemotherapy, 1 with radiation, 6 with both chemotherapy and radiation, and 17 did not have any treatment before CPDD combination. 31 of the 38 cases (81. 5%) demonstrated objective responses lasting for 2 months or more. These responses were partial in 19 and complete in 12 cases. Hematologic toxicity was moderate and with reversible anemia developing in 71% of patients. Gastrointestinal side effects from CPDD were universal. HMM gastrointestinal toxicity necessitated discontinuation of the drug in 5 patients. Severe nephrotoxicity was observed in 2 patients but was reversible. There were no drug - related deaths.

ovarian cancer

ovarian cancer

Hematologic toxicity

anemia

gastrointestinal toxicity

nephrotoxicity

cis - platinum

adriamycin

cyclophosphamide

hexamethylmelamine

cisplatinum

CPDD

adriamycin

cyclophosphamide

hexamethylmelamine

HMM

CPDD

CPDD

HMM

CPDD

anemia

CPDD

anemia

CPDD

anemia

CPDD

nephrotoxicity

CPDD

nephrotoxicity

CPDD

nephrotoxicity

CPDD

gastrointestinal toxicity

CPDD

gastrointestinal toxicity

CPDD

gastrointestinal toxicity


Input: Nontraumatic dissecting aneurysm of the basilar artery. A case of nontraumatic dissecting aneurysm of the basilar artery in association with hypertension, smoke, and oral contraceptives is reported in a young female patient with a locked - in syndrome.

dissecting aneurysm

dissecting aneurysm

hypertension

locked - in syndrome

oral contraceptives

oral contraceptives

dissecting aneurysm

oral contraceptives

dissecting aneurysm


Input: Propylthiouracil - induced hepatic damage. Two cases of propylthiouracil - induced liver damage have been observed. The first case is of an acute type of damage, proven by rechallenge; the second presents a clinical and histologic picture resembling chronic active hepatitis, with spontaneous remission.

Propylthiouracil

propylthiouracil

hepatic damage

liver damage

chronic active hepatitis

Propylthiouracil

chronic active hepatitis

propylthiouracil

chronic active hepatitis

Propylthiouracil

hepatic damage

Propylthiouracil

liver damage

propylthiouracil

hepatic damage

propylthiouracil

liver damage


Input: Studies on the bradycardia induced by bepridil. Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non - specific anti - tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life - support medium for isolated sino - atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10 (- 6) M. This effect was dose - dependent up to concentrations of 5 X 10 (- 5) M, whereupon blockade of sinus activity set in. Bepridil at a dose of 5 X 10 (- 6) M, induced a concomitant reduction in AP amplitude (falling from 71 + / - 8 mV to 47 + / - 6 mV), maximum systolic depolarization velocity (phase 0) which fell from 1. 85 + / - 0. 35 V / s to 0. 84 + / - 0. 28 V / s, together with maximum diastolic depolarization velocity (phase 4) which fell from 38 + / - 3 mV / s to 24 + / - 5 mV / s. In vivo injection of bepridil at a dose of 5 mg / kg (i. v.) into 6 anaesthetized dogs which had undergone ablation of all the extrinsic cardiac afferent nerve supply, together with a bilateral medullo - adrenalectomy, caused a marked reduction in heart rate which fell from 98. 7 + / - 4. 2 beats / min to 76 + / - 5. 3 beats / min sustained for more than 45 min. It is concluded that bepridil reduces heart rate by acting directly on the sinus node. This effect, which results in a flattening of the phase 0 and phase 4 slope, together with a longer AP duration, may be due to an increase in the time constants of slow inward ionic currents (already demonstrated elsewhere), but also to an increased time constant for deactivation of the outward potassium current (Ip).

bradycardia

anginal attacks

bradycardia

tachycardial

bepridil

Bepridil

bepridil

KCl

Bepridil

bepridil

bepridil

potassium

bepridil

bradycardia

bepridil

bradycardia

Bepridil

bradycardia

Bepridil

bradycardia

bepridil

bradycardia

bepridil

bradycardia

Bepridil

bradycardia

Bepridil

bradycardia

bepridil

bradycardia

bepridil

bradycardia

bepridil

bradycardia

bepridil

bradycardia


Input: Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane. A 69 - year - old man operated for acute cholecystitis under methoxyflurane anesthesia developed postoperatively a hepatic insufficiency syndrome and renal tubular acidosis. Massive bleeding appeared during surgery which lasted for six hours. Postoperative evolution under supportive therapy was favourable. Complete recovery was confirmed by repeated controls performed over a period of one year after surgery.

Hepatitis

renal tubular acidosis

acute cholecystitis

hepatic insufficiency syndrome

renal tubular acidosis

bleeding

methoxyflurane

methoxyflurane

methoxyflurane

renal tubular acidosis

methoxyflurane

renal tubular acidosis

methoxyflurane

renal tubular acidosis

methoxyflurane

renal tubular acidosis

methoxyflurane

Hepatitis

methoxyflurane

Hepatitis


Input: Pituitary response to luteinizing hormone - releasing hormone during haloperidol - induced hyperprolactinemia. The effects of a 6 - hour infusion with haloperidol on serum prolactin and luteinizing hormone (LH) levels was studied in a group of male subjects. Five hours after starting the infusions, a study of the pituitary responses to LH - releasing hormone (LH - RH) was carried out. Control patients received infusions of 0. 9% NaCl solution. During the course of haloperidol infusions, significant hyperprolactinemia was found, together with an abolished pituitary response to LH - RH, as compared with responses of control subjects.

haloperidol

haloperidol

NaCl

haloperidol

hyperprolactinemia

hyperprolactinemia

haloperidol

hyperprolactinemia

haloperidol

hyperprolactinemia

haloperidol

hyperprolactinemia

haloperidol

hyperprolactinemia

haloperidol

hyperprolactinemia

haloperidol

hyperprolactinemia


Input: Antirifampicin antibodies in acute rifampicin - associated renal failure. 5 patients with acute renal failure (3 with thrombopenia and hemolysis) induced by the reintroduction of rifampicin are described. No correlation was found between the severity of clinical manifestations and the total dose taken by the patients. In all but 1 patient, antirifampicin antibodies were detected. Antibodies suggested to be of the IgM class were detected in all 3 patients with hematological disorders. The pattern of non - specific acute tubular necrosis found in the 2 biopsied patients, indistinguishable from that of ischemic origin, raised the possibility of a vascular - mediated damage. In 3 patients, the possibility of a triggering immunoallergic mechanism is discussed.

rifampicin

rifampicin

renal failure

acute renal failure

thrombopenia

hemolysis

hematological disorders

acute tubular necrosis

rifampicin

hemolysis

rifampicin

hemolysis

rifampicin

thrombopenia

rifampicin

thrombopenia

rifampicin

acute tubular necrosis

rifampicin

acute tubular necrosis