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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 433 records · Page 24Linked to original sources

[Effect of nitroglycerin plasters on hemodynamics and stress tolerance of patients with coronary heart disease].

The haemodynamic and antianginous efficacy of percutaneous nitroglycerin was evaluated in 24 patients with coronary heart disease. Groups of 8 patients each received one, two or four patches (nitroglycerin liberation 5 mg per patch within 24 hours). Prior to application and after 1 and 2 hours cardiac frequency, arterial and pulmonary arterial pressures and exercise tolerance were assessed. Cardiac frequency and arterial pressure showed no relevant changes after application of patches. The mean pulmonary arterial pressure decreased after application of one or two plasters by 18.5 and 22.2% at rest and by 12.7 and 21.1%, respectively, during exercise. The working capacity showed a trend towards improvement only. With four nitroglycerin patches the mean pulmonary arterial pressure at rest was lower by 26.2% and during exercise by 39.1%. The working capacity rose significantly by 48.7%. Comparison of these effects with oral single dosage of 20 mg 5-isosorbide mononitrate (ISMN) showed that two simultaneously administered plasters did not achieve efficacy of 20 mg 5-ISMN, four plasters, however, were more effective.

Adult↗

Evidence against the involvement of a noradrenergic mechanism in the release by diazepam of novelty-induced hypophagia in rats.

The involvement of noradrenergic processes in both the behavioral suppression and release of food intake induced by diazepam, was investigated using the novelty-induced inhibition of food consumption model. Clonidine (7.5-60 micrograms/kg i.p.) and another alpha 2-noradrenergic receptor agonist, guanfacine (0.25-1 mg/kg i.p.), increased the food intake of rats placed in an unfamiliar situation. The effects of clonidine (15 micrograms/kg) were antagonized by yohimbine (0.5-2 mg/kg i.p.). Clonidine (7.5 micrograms/kg) was unable to enhance the efficacy of diazepam (0.5 and 1 mg/kg i.p.) in stimulating food consumption, whereas yohimbine (0.5-2 mg/kg) did not reduce and even increased the potency of diazepam (2 mg/kg) to facilitate food intake. These findings suggest that although noradrenergic processes (and in particular alpha 2-adrenoreceptors) are involved in the hyponeophagia model they do not mediate the releasing effect exerted by benzodiazepines on novelty-induced suppression of food intake.

Animals↗

[Immunoglobulin A glomerulonephritis. Epidemiology in a population of 250 000 inhabitants].

Between April 1, 1975 and May 1, 1982, 192 cases of primary glomerulonephritis were histologically diagnosed in the Nephrology centre of a health district with 250 000 inhabitants; 58 (30.2%) of the lesions were IgA glomerulonephritis. All patients were born and lived in that district. At the end of the period under review the prevalence of IgA glomerulonephritis was evaluated at 1/10 000 and its incidence at 2.5/100 000 per year. The disease began in subjects under 35 years of age in 65% of the cases, with a peak between 16 and 25 years. Thirty-seven patients were symptom-free, and the condition was diagnosed either at recruitment in the army (15 cases; 25.2%) or during the annual medical examination of industrial workers (19 cases; 39.7%). At the end of the study, 21 patients (36%) had renal failure, and 5 of these (8.5%) were under periodical haemodialysis. This study shows how valuable it would be from a socio-economic point of view if the role played by public health institutions in detecting the disease were confirmed and if its prevalence among the French population were precisely known.

Adolescent↗

Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat.

The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 microgram in 0.4 microliter) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 micrograms in 0.5 microliter) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10(-5)-10(-4)M in 0.2 microliter) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.

5,7-Dihydroxytryptamine↗

Stimulation of beta-adrenergic receptors and spontaneous motor activity in mice.

The effects of 3 beta-adrenergic agonists (clenbuterol, isoproterenol and salbutamol) on the spontaneous motor activity of mice were studied. The present research indicated that motor activity was significantly decreased 30 minutes after IP injection of either clenbuterol (0.06 mg/kg), isoproterenol (0.5 mg/kg) or salbutamol (2 mg/kg). Hypomotility induced by clenbuterol was also significantly antagonized by propranolol in doses ranging from 1 to 8 mg/kg and by penbutolol in doses from 0.03 to 0.5 mg/kg. However, practolol, which does not cross the blood brain barrier, did not antagonize the effect of clenbuterol. Therefore, it may be hypothesized that beta adrenergic agonists decrease motor activity by a central mechanism. It was also found that tachyphylaxis or resistance to treatment, observed in cardiovascular and bronchopulmonary systems with beta-adrenergic agonists, developed after 7 injections of clenbuterol (0.25 mg/kg IP, twice daily) in the behavioral model of spontaneous motor activity in mice.

Adrenergic beta-Agonists↗

Disappearance of the decrease in biting behavior induced by clenbuterol, a beta-adrenergic agonist, after chronic administration.

The beta-adrenergic agonist clenbuterol decreased interest in food in starved mice, 30 minutes after administration. This effect disappeared after repeated treatment with clenbuterol (0.25 mg/kg, twice daily). Three chronic injections were sufficient to prevent the effect of an acute dose of clenbuterol (0.125 mg/kg) up to 45 hours after treatment.

Aggression↗

Comparison of the stimulatory effects of eight antiparkinsonian drugs.

The effects of eight antiparkinsonian anticholinergic drugs on motor activity in mice were studied. Trihexyphenidyl, biperiden, benztropine, etybenztropine, procyclidine and tropacine clearly stimulated motor activity. Orphenadrine did not change motor activity, and profenamine had sedative properties. The classification of these drugs by order of their effect on this animal model does not agree with the classification proposed by Deniker et al (1980).

Animals↗

Searching-waiting strategy: a candidate for an evolutionary model of depression?

The model proposed here assumes that depressive disorders could reflect an extreme state of a current behavioral strategy. According to this model, a subject facing a problem of survival without apparent solution may choose between two behavioral patterns: searching for a solution or waiting for that solution to occur. This choice can be made after one or several estimations of the cost and benefit attached to each of these alternatives. Two of the main behavioral models of depression are interpreted according to this model: namely, infant response to maternal separation in monkeys and "behavioral despair" in rodents. Practical and theoretical consequences of this model are discussed.

Adaptation, Biological↗

Metronidazole kinetics and bioavailability in patients undergoing gastrointestinal surgery.

Kinetics and bioavailability of metronidazole were studied in 17 patients admitted in our emergency care unit for gastrointestinal surgery. All were treated with intravenous metronidazole (500 mg three times a day) before, during, and for 4 days after surgery. Seven of the patients continued the intravenous regimen and seven were switched to oral therapy with the same dose and dosing interval for 4 additional days. Kinetic evaluations were performed at steady state on days 4 and 8. The main unexpected result was a consistent 51% increase in AUC with no increase in elimination t 1/2 when intravenous was changed to oral therapy. This change was accompanied by an upward 75% shift in the trough metronidazole plasma concentrations. There was no change when patients remained on intravenous metronidazole. Reduction of clearance on oral treatment appears to be the most likely explanation.

Administration, Oral↗

Pharmacological classification of benzamides.

The problem of classifying benzamides is, in general, the same as classifying neuroleptics. A pharmacological classification of neuroleptics can be established on the basis of the following criteria: specificity of action on dopaminergic receptors; penetration into the CNS; dopaminergic profile in the CNS; relative binding with respect to subclasses of DA; preferential antagonism of certain effects of apomorphine; preferential affinity for dopaminergic structures; activating effects on DA systems at low doses; different clinical effects: antiemetic, psychiatric (antihallucinatory and disinhibitory), neurologic. A relationship between biochemical, behavioural and clinical effects is proposed: antihallucinatory effect: decrease of dopaminergic function; disinhibitory effect: increase of dopaminergic function. We emphasize the problem of doses used because the different effects occurred for a given drug at different doses. This hypothesis suggests that positive symptomatology of schizophrenia is related to hyperdopaminergic activity, negative symptomatology is related to hypodopaminergic activity. Classification of benzamides: metoclopramide: peripheral dopaminolytic activity antiemesis without psychiatric or neuroleptic effects with low doses. sulpiride, tiapride, DAN 2163: peripheral effects + preferential blockade of D3 and D4 receptors, central DA activation with low doses, disinhibitory effects. With high doses, decrease of specificity for subclasses of DA receptors, central DA inhibition, antihallucinatory effects but little extrapyramidal symptomatology and sedation. sultopride: central DA inhibition, antihallucinatory effects, sedative and neurological effects.

Animals↗

Rapidly progressive ('crescentic') glomerulonephritis and monoclonal gammapathies.

In 3 patients rapidly progressive glomerulonephritis revealed plasma cell dyscrasia in 2 cases and Waldenstrom's macroglobulinemia in the 3rd. Renal biopsy showed proliferative glomerulonephritis with marked endo- and extracapillary (crescentic) proliferation. In case 1, corticosteroids and cyclophosphamide favorably influenced the course of the disease. The 2nd patient was not treated and went on to maintenance hemodialysis. In the 3rd case, plasma exchange and cytotoxic drugs allowed discontinuation of hemodialysis. Thirteen other cases of proliferative glomerulonephritis associated with monoclonal gammapathies have been described in the literature, including 3 with crescents. B-cell dyscrasia should be considered a possible etiology in a patient with crescentic glomerulonephritis. In such case we show that treatment of the hematologic disorder can be followed by a dramatic improvement of renal function.

Aged↗

Ketanserin, a serotonin antagonist. Administration in patients with acute respiratory failure.

Increased release of serotonin (5-hydroxytryptamine, 5-HT) can play a significant role in the development of acute respiratory failure. The hemodynamic effects of ketanserin, a selective inhibitor of 5-HT2 receptors, were studied in eight patients who developed acute respiratory insufficiency after an episode of circulatory shock. Administration of ketanserin was associated with reductions in systemic and pulmonary artery pressures, without significant change in heart rate or cardiac output. Concomitant decreases in hemoglobin and protein concentrations suggested an associated increase in plasma volume. These changes were attributed to an increased peripheral pooling of blood related to vasodilation. Arterial oxygenation and pulmonary shunt were unaffected. These results indicate ketanserin represents a promising vasoactive agent for treatment of acute respiratory failure in critically ill patients.

Adult↗