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Biomedical subjects

P Simon

Publications and source records attributed to P Simon.

At least 469 records · Page 26Linked to original sources
PubMed1983

[What phase IV should be like for an anxiolytic agent].

The phase IV of an anxiolytic preparation comprises all studies done after marketing. Specialized complementary studies allow to better define psychopharmacological profile: reaction to provoked stress, anxiolytic and sedative components, correlation blood levels - clinical effects, studies in elderly patients, mixed anxiety-depression syndromes. Surveillance studies are aimed to detect as soon as possible rare and serious adverse reactions. According to the situation the following studies are undertaken: system of data collection and processing for spontaneous reports, prospective follow-up studies of a large group of patients to detect only serious events, intensive follow-up to detect any potentially interesting event. Studies of interactions: systematic studies (alcohol, hypnotics) or sporadic spontaneous reports. Large multicentric uncontrolled studies may have an interest if they are done with an heuristic purpose, in order to use descriptive statistical tools, to generate hypotheses which should be independently confirmed afterwards.

Anti-Anxiety Agents↗
PubMed1983

The value of the reserpine test in psychopharmacology.

Numerous tests have been proposed to search for a possible antidepressive action. Many of these tests are based on a reversal of different reserpine effects, an approach justified mainly by the use of most the classic or new antidepressants. Three effects of reserpine were examined in mice: hypothermia, ptosis and akinesia. All tests were performed with reserpine 2.5 mg/kg, and the drugs were injected 4 h after reserpine administration. In these three models, we studied the relatively specific effects of 21 drugs known for their influence on the metabolism or action of norepinephrine (noradrenaline), serotonin and dopamine. Our results suggest that hypothermia antagonism is only obtained with drugs stimulating beta-adrenergic receptors directly or indirectly, ptosis antagonism with those stimulating alpha-adrenergic or serotonergic receptors, and akinesia antagonism with those stimulating dopaminergic receptors.

Animals↗
PubMed1982

U 43,465F: a benzodiazepine with antidepressant activity? Interaction with Ro 15-1788 and d,1-propranolol.

U-43,465F (8-chloro-1-[2-(dimethylamino)ethyl]-6-phenyl-4H-s-triazolo [4,3-a][1,4]benzodiazepine p-toluene sulfonate) showed two fold activity at 32 mg/kg i.p.: antipunishment activity inhibited by the benzodiazepine receptor antagonist Ro 15-1788, and an antidepressant-like reversal of apomorphine-induced hypothermia, antagonized by the beta-adrenergic receptor blocker d,1-propranolol. U-43,465F hence produced effects not mediated by benzodiazepine receptors and these effects might be related to antidepressant activity.

Alprazolam↗
PubMed1982

[Side effects and risks of benzodiazepines].

If benzodiazepines rank amongst the less harmful drugs, they are not completely safe. As all other drugs, they must be evaluated in relation with their risk/benefit ratio knowing that their side effects must be assessed for each patient and that they may vary according to indication, dosage, routes of administration and pharmacokinetic differences between the molecules. The authors mainly study: vigilance disorders and performance impairment, memory loss, behaviour disturbances, exceptional toxicomania risk, teratogen effects, not proved to this date, acute overdosage, interaction with other sedative psychotropic drugs (CNS depressors, imipramine). In conclusion, the authors underline the importance of the use of benzodiazepines and their success which is a social phenomenon.

Anti-Anxiety Agents↗
PubMed1982

Size determination of an equilibrium enzymic system by radiation inactivation: theoretical considerations.

Radiation inactivation of complex enzymic systems is currently used to determine the enzyme size and the molecular organization of the components in the system. We have simulated an equilibrium model describing the regulation of enzyme activity by association of the enzyme with a regulatory unit. It is assumed that, after irradiation, the system equilibrates before the enzyme activity is assayed. Our theoretical results show that the target-size analysis of these numerical data leads to a bad estimate of the enzyme size. Moreover, some implicit assumptions such as the transfer of radiation energy between non-covalently bound molecules should be verified before interpretation of target-size analysis. It is demonstrated that the apparent target size depends on the parameters of the system, namely the size and the concentration of the components, the equilibrium constant, the relative activities of free enzyme and enzymic complex, the existence of energy transfer, and the distribution of the components between free and bound forms during the irradiation.

Enzyme Activation↗
PubMed1982

[Polycythaemia in a haemodialyzed anephric patient with hepatitis. Demonstration of erythropoietin secretion (author's transl)].

A 45-year-old woman who had undergone bilateral nephrectomy and splenectomy and who had been under haemodialysis since 1966 developed non-A non-B cytolytic hepatitis in October, 1978. Her haematocrit and haemoglobin levels had been stable at 39% and 6 g/dl respectively for more than one year when, two months after the onset of hepatitis, spontaneous improvement of anaemia was observed. This persisted side-by-side with hepatic cytolysis until march, 1980. At that time, the total red cell volume was 24% above normal, the haematocrit was 41% and the haemoglobin level 13 g/dl. It was than that serum erythropoietin was measured and found to be 82 mU/ml (normal values : 5-10 mU/ml). During the following months hepatic cytolysis and polycythaemia gradually subsided, and the serum erythropoietin level decreased. This case suggests that extrarenal erythropoietin can be secreted by the liver in anephric adults with uraemia, that hepatocytes undergoing regeneration after cytolysis in adults may have the same capability or erythropoietin secretion as in foetuses, and that in some haemodialyzed patients bone marrow responses to erythropoietin remains unaltered.

Erythropoietin↗
PubMed1982

Pharmacokinetics of sulfamethoxazole--trimethoprim combination during chronic peritoneal dialysis: effect of peritonitis.

The pharmacokinetics of the fixed combination trimethoprim sulfamethoxazole (TMP--SMZ), including peritoneal transfer, has been studied in patients with end-stage renal disease treated by peritoneal dialysis, intermittent in 18 cases and continuous ambulatory dialysis in 6 cases. After a single oral dose of TMP 4 mg and SMZ 20 mg per kg, peak serum levels of approximately 2.0 micrograms/ml TMP and 28 micrograms/ml SMZ were achieved at 4 hours for TMP, and at 6 hours for SMZ. The protein binding of TMP was 34.7 +/- 1.1% and its distribution volume was 2.2 +/- 0.51/kg. Total plasma clearance of TMP was 66.2 +/- 11.5 ml/min, peritoneal dialysance was 5.1 +/- 0.5 ml/min, and renal clearance was negligible. The protein binding of SMZ was 48.0 +/- 1.4% and the distribution volume was 0.55 +/- 0.071/kg. Total plasma clearance of SMZ was 26.2 +/- 5.7 ml/min, peritoneal dialysance was 1.2 +/- 0.2 ml/min, and renal clearance was negligible. The half lives of TMP and SMZ were 23.7 +/- 4.0 h and 18.1 +/- 3.5 h, respectively. The peritoneal dialysance both of TMP and SMZ after oral administration was very low. In contrast the absorption after intra-peritoneal administration is high. Peritoneal absorption was increased during peritonitis. In patients with peritonitis, the intra-peritoneal administration of TMP-SMZ resulted in an immediate high local concentration, and a serum concentration of both drugs in the therapeutic range within 6 to 12 h.

Administration, Oral↗
PubMed1982

Pharmacology of hypnotics.

Sedative hypnotics belong to several chemical classes and thus have heterogeneous pharmacodynamic properties. Among various ways of approaches, conventional pharmacology using animal models allows one to define a common pharmacological profile. It still remains the best predictive tool of hypnotic efficacy in man. The study of discriminative properties is a useful extension of these conventional models. Electrophysiological and biochemical studies allow primarily to approach the problems of the sites and mechanisms of action, but only begin at the moment to lead to practical applications.

Aggression↗
PubMed1982

Diflunisal versus placebo for treatment of pain in general practice.

The efficacy and safety of diflunisal versus placebo in the treatment of pain were compared in a multicenter, double-blind study of 1,037 patients treated for seven days by general practitioners. A statistically significant (P less than 0.001) difference in favor of diflunisal was seen using four evaLuation criteria. The incidence of side effects was generally low with both treatments; nevertheless, the number of patients suffering at least one side effect was greater after diflunisal than after placebo (P less than 0.05). A comparison of the profile of responders to diflunisal and to placebo showed no particular pattern.

Clinical Trials as Topic↗
PubMed1982

[Mytomycin C nephrotoxicity. 3 new cases and review of the literature].

Three women with adenocarcinoma of cardia, adenocarcinoma of liver or ileum carcinoid tumor, respectively, were treated with mitomycin C (MMC) and 5-fluoro-uracil (5-FU). Two patients had renal impairment 6 and 11 months, the third as early as 8 weeks after initiation of MMC therapy. In the three cases, blood transfusions appeared to play an aggravating role inducing respiratory distress, microangiopathic hemolytic anemia and thrombocytopenia, and to accelerate progression of renal failure. Death occurred in the first patient; terminal renal insufficiency necessitated hemodialysis treatment in the second, and after 10 plasma exchanges, renal failure remained stable in the third. Light and electron microscopy study of the kidney revealed renal lesions compatible with thrombotic microangiopathy in all cases. Mesangiolysis with swollen nuclei of endothelial cells in most glomeruli was also seen in two cases. We compared our observations with the findings found in 30 previously reported cases. These observations substantiate the renal toxicity of mitomycin C.

Adenocarcinoma↗
PubMed1981

Enhancement of cocaine-induced hyperactivity in mice by benzodiazepines: evidence for an interaction of GABAergic processes with catecholaminergic neurons?

The effects of nine benzodiazepines on the locomotor stimulation induced in mice by cocaine (4 mg . kg-1 i.p.) were studied. These benzodiazepines markedly enhanced cocaine-induced hyperactivity. This effect was observed at low doses, e.g. doses at least 8 times lower than those required to depress the stimulation caused by cocaine. Nitrazepam-induced enhancement of the hyperactivity elicited by cocaine was reduced or suppressed by blocking dopaminergic receptors with pimozide (0.015--0.03 mg . kg-1), by interrupting GABAergic transmission with picrotoxin (0.25--0.5 mg . kg-1) or blocking alpha- or beta-adrenergic receptors with prazosin (0.25 mg . kg-1) or dl-propranolol (4 mg . kg-1) respectively. At these doses, neither pimozide, picrotoxin, prazosin nor propranolol were able to modify the spontaneous locomotor activity or the stimulation elicited by cocaine alone. Strychnine (0.25--0.50 mg . kg-1) or methysergide (2 mg . kg-1) failed to alter the enhancement by nitrazepam of cocaine-induced hyperactivity. These results suggest that an interaction of benzodiazepines with some catecholaminergic processes, either directly or through the involvement of a GABAergic link, may account for their facilitatory activity on cocaine-induced locomotor stimulation.

Animals↗
PubMed1981

Effect of chronic lithium treatment on isolation-induced behavioral and biochemical effects in mice.

The following effects were induced in mice by a prolonged of isolation (6-7 weeks from weaning): (1) reduction in motor activity; (2) reduction in the effect of oxotremorine on rectal temperature; (3) increase in the response to salbutamol, a beta-adrenergic stimulant. Chronic lithium treatment (2 mg/ml in the drinking water during the last 3-4 weeks of isolation) prevented these phenomena. The number and affinity of beta-adrenergic receptors in the whole mouse brain (excluding the cerebellum) was unmodified by either isolation or by lithium. It is suggested that lithium blocks isolation-induced hypersensitivity, especially of the beta-adrenergic system; this mechanism may be involved in the therapeutic action of lithium.

Animals↗