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Biomedical subjects

G Perret

Publications and source records attributed to G Perret.

At least 55 records · Page 3Linked to original sources

Effect of nifedipine and nitrendipine on insulin release in non-diabetic obese patients: a double-blind, placebo-controlled study.

Calcium antagonists are known to decrease insulin release in vitro. In vivo, their effects on insulin secretion and glucose tolerance are more controversial. We carried out a double-blind, double-dummy, controlled trial to study the effects of nifedipine (40 mg/day; n = 9), nitrendipine (20 mg/day; n = 9) and placebo (n = 10) on insulin release in 3 parallel groups of obese patients with mild or transient hypertension and a normal oral glucose tolerance test. The treatment lasted one week. Patients were asked not to modify their diet throughout the trial, and their body weight did not vary significantly. A 2-hour i.v. glucose tolerance test was performed twice in every patient, just before the first drug intake and one hour after the last one. The following parameters were measured or calculated during each test: basal, peak and early phase levels of blood glucose, insulin and C-peptide; glucose disappearance rate; and glucose, insulin and C-peptide incremental areas under the time-curves. On day 1, the 3 groups of patients were comparable for age, sex, body weight and every biological parameter. One-way analysis of variance did not show any significantly different evolution of those parameters between the 3 treatment groups, but calcium antagonists tended to slightly reduce the early phase of insulin release compared with placebo.

Adolescent↗

Effect of nifedipine on thyrotropin, prolactin, and thyroid hormone release in man: a placebo-controlled study.

Nifedipine (10 mg tid) or placebo was administered in a randomized double-blind trial for 1 wk to 2 groups of 10 mildly hypertensive euthyroid patients. Hormonal concentrations (thyrotropin [TSH], prolactin [PRL], thyroxin, triiodothyronine, and reverse triiodothyronine) before and during a TRH test were assessed in the 2 groups before (D0) and after (D7) each treatment. Parameters of the TRH test were determined (peak values, area under the curve [AUC], release [Kr], and elimination [Ke] rate constants) and their D7:D0 ratios were compared in the 2 groups. The TSH (peak values and Kr) and PRL (peak values and AUC) responses to TRH were significantly decreased in the nifedipine group compared to the placebo group. Neither basal nor TRH-stimulated thyroid hormone levels were modified. These results confirm experimental data but seem to be clinically irrelevant.

Adult↗

Effective high-performance liquid chromatographic determination of glafenine in plasma: pharmacokinetic application.

A high-performance liquid chromatographic method for an effective determination of glafenine and its main metabolite, glafenic acid, is described. The assay involves separate extraction procedures for glafenine and for its metabolite, but the same internal standard (floctafenine) and the same chromatographic conditions (including a 5-micron C8 column, a quaternary solvent mixture of water-acetonitrile-diethylamine-acetic acid and an ultraviolet detector set at 360 nm). For 1 ml of plasma, the detection limit is 0.05 mg/l for glafenine and 0.25 mg/l for glafenic acid. Compared with previously described techniques, this assay uses a very low glafenine linearity range, which allows the true pharmacokinetics of this drug to be described for the first time.

Chromatography, High Pressure Liquid↗

Use of a pharmacokinetic model to characterize the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (THR) in man.

On the basis of a pharmacokinetic model using the data of a TRH test and without the use of radio-isotope tracers, a simple procedure of estimation of PRL and TSH TRH-stimulated release and elimination half-lives is presented. TRH tests were performed in 33 healthy subjects and their data were used to calculate the kinetic parameters of each subject. Elimination half-lives of TSH and PRL were found to be respectively (mean +/- SD in min) 63 +/- 7.4 and 35 +/- 2.8. Release half-lives were 8.2 +/- 1.3 for TSH and 5 +/- 0.4 for PRL. The usefulness of the procedure in the evaluation of drug effects on pituitary secretion in man and the comparison with the literature data are discussed.

Adult↗

Effect of diosmin upon red blood cell deformability and osmotic fragility. Relationship with lipid content.

Rats were treated by ingesting forcibly 2 ml of a suspension of four different doses (100, 200, 300 and 400 mg/kg) of diosmin in carboxymethylcellulose (CMC) and were killed immediately or after 3 or 6 hours of fasting. Animals treated by CMC only in a similar way (gavage) exhibited a fall in red blood cell (RBC) membrane cholesterol and an increase in RBC rigidity at the third hour while osmotic fragility remained stable. Diosmin treatment opposed the rise in RBC rigidity evoked by the gavage and induced a dose-dependent decrease of the RBC membrane cholesterol over phospholipid ratio.

Animals↗

Remission of idiopathic nephrotic syndrome after treatment with cyclosporin A.

Nephrotic syndrome in minimal change lipoid nephrosis and focal segmental glomerulosclerosis may be due to alteration of glomerular anionic sites by a lymphokine. Six adults with nephrotic syndrome who were resistant to treatment with corticosteroids and immunosuppressants were treated with cyclosporin A. In three patients with minimal change lipoid nephrosis who had been nephrotic for 3.5 to 23 years proteinuria resolved within 12 to 42 days. Subsequently, these patients became dependent on cyclosporin A. In three patients with focal segmental glomerulosclerosis who had been nephrotic for four to six years mean (SD) 24 hour urinary protein decreased from 14.7 (8.4) g to 3.6 (0.6) g within 20 to 25 days, serum albumin concentration rose, and oedema subsided. One patient died of myocardial infarction when still in partial remission after 11 weeks' treatment. Two patients remained proteinuric despite continuing treatment with cyclosporin A, but control of sodium balance was easy and serum albumin concentrations remained higher than without cyclosporin A. In all patients renal function improved during treatment. These preliminary results show that cyclosporin A may be effective in the treatment of patients with nephrotic syndrome that resists every other form of treatment and especially in the treatment of those with minimal change lipoid nephrosis. The results are in keeping with a T lymphocyte mediated mechanism of minimal change lipoid nephrosis and focal segmental glomerulosclerosis, but they also suggest that minimal change lipoid nephrosis and focal segmental glomerulosclerosis are separate entities.

Adult↗

Effect of a short-term oral administration of cimetidine and ranitidine on the basal and thyrotropin-releasing hormone-stimulated serum concentrations of prolactin, thyrotropin and thyroid hormones in healthy volunteers. A double-blind cross-over study.

Cimetidine (400 mg b.d.), ranitidine (150 mg b.d.) and placebo were administered for 1 week to 6 healthy male volunteers in a randomized double-blind cross-over fashion. Hormonal concentrations before and after a TRH test were assessed before and after each treatment. A spontaneous decrease in the hormonal response to TRH was observed after placebo treatment. Both cimetidine and ranitidine induced a significant increase in basal prolactin (PRL) values. Neither TSH nor T3 were modified by cimetidine or by ranitidine. The basal concentration of reverse T3 was increased during cimetidine treatment. There was a significant rise in post-TRH T4 after cimetidine and ranitidine administration. These results suggest a role for histamine H2 receptors in the secretion of PRL and T4. Moreover, cimetidine affects the hepatic metabolism of thyroid hormones.

Adult↗

Evidence of direct thyroid-stimulating action of thyrotropin-releasing hormone by perifusion of rat thyroid fragments.

The possibility that TRH has a direct thyroid-stimulating action has never been reported. A number of studies have shown a rise in serum concentrations of thyroid hormone after stimulation with TRH, without a rise in TSH secretion. This has led us to test TRH with rat thyroid fragment perifusion. Significant T4 release was observed for TRH concentrations as low as 1.7 X 10(-11) M. A dose-response curve was determined. The response was immediate, reaching a peak after the sixth minute and continuing for 15 min after the stimulation had ceased. This kinetic pattern is different from the one observed with TSH and with theophylline and suggests that a different mechanism may be involved. TRH seems to be capable of directly stimulating both the secretion of the pituitary hormone (TSH) and the corresponding peripheral gland, like LHRH, which also acts directly on the Leydig cells of the testis.

Animals↗

[Ulcerogenic potential of corticoids in man: a reality or methodologic artifact?].

It is generally accepted that glucocorticoids are ulcerogenic. The different pharmacological, biological and clinical arguments on which this opinion is founded are reviewed. It is concluded that, particularly in pneumology, none of them is sufficiently sound to justify the prophylactic measures generally systematically used. In fact it appears that glucocorticoids are not primary offenders by rather potentiate ulcerogenesis. Prophylactic measures are therefore indicated only in ulcerogenic conditions such as association with non steroidal anti-inflammatory agents or in some pathological situations such as rheumatoid arthritis and severe cirrhosis. These conditions are generally not encountered in pneumology and therefore the ulcerogenic risk in this case can be considered as non existent.

Adrenal Cortex Hormones↗

Compared effect of propranolol and acebutolol on serum thyroid hormones' levels in euthyroid and hyperthyroid patients: a randomized study.

An open randomized study involving 57 subjects, 40 euthyroid and 17 hyperthyreotic, was undertaken to compare the effect of two beta-adrenergic blocking drugs, propranolol (120 mg/day) and acebutolol (600 mg/day), on the thyroid hormones serum level. In hyperthyreotic as well as in euthyroid subjects, propranolol evoked a fall in T3, an increase in reverse T3 and therefore a decrease in the T3/rT3 ratio. Acebutolol caused a decrease in T3 and in the T3/rT3 ratio only in euthyroid subjects. The only significant variation in the hyperthyroid acebutolol treated group was a decrease in reverse T3, perhaps spontaneous. TBG and TSH concentrations remained stable under treatment in all the groups. The relation of these effects with the existence of a membrane stabilizing activity displayed by propranolol as well as by acebutolol is discussed.

Acebutolol↗

in vivo Ageing of human erythrocytes and cell-surface labeling by metaperiodate and sodium borotritide.

Young and old human erythrocytes, separated in vitro according to age, were labeled at the surface-sialic acid residues by sodium periodate and borotritide treatment. No qualitative difference was observed between the sialic acid derivatives of young- and old-erythrocyte membranes. The number of labeled residues was significantly decreased in the in vivo aged erythrocytes (12 +/- 2.8 X 10(6); n = 8) when compared to the young ones (19.4 +/- 2.8 X 10(6); n = 8). Analysis of the labeled glycoproteins by sodium dodecyl sulfate gel-electrophoresis showed that this decrease affects the PAS-1, PAS-4, PAS-2, and PAS-3 bands (glycophorins A and B) of the old-erythrocyte membranes.

ABO Blood-Group System↗

Lecithin content estimate of human alveolar lining layer: comparison with mouse, rat and rabbit.

Saturated as well as total lecithins recovered by lung lavage are linearly correlated with the species body weight and with their respiratory rate. The value of the ratio:amount of saturated lecithins recovered by lung lavage to theoretical minimum amount needed to form a monomolecular film over the alveolar surface at functional residual capacity decreases linearly according to the respiratory rate of the species examined. In man this ratio is lower than 1 (0.45 +/- 0.11) and suggests the possible existence of a discontinuous mono molecular film of lipidic surfactant.

Animals↗

Red cell ageing: phagocytosis and life-span of young and old erythrocytes fractionated by centrifugation.

Young and old red blood cells, separated by centrifugation on the basis of differences in cell density, were submitted to phagocytosis by either autologous human alveolar macrophages or syngeneic murine bone-marrow macrophages. Young cells adhere to macrophages, but to a much smaller extent than old ones. The influence of both type and quality of the separation procedure on the differences observed between the two erythrocyte subpopulations is discussed in the light of the half-life times of murine young and old red blood cells. Fractionation according to age was obtained following the method of Murphy (1973) and glutamate oxalo-acetate transaminase activity was measured and used as an indicator of both cell age and separation.

Animals↗

[Pulmonary diffusion of gentamicin administered by the direct intravenous route].

Gentamicin diffusion in pulmonary parenchyma was studied in 10 adult patients with normal renal functions before undergoing thoracic surgery. This aminoside was given in a one time dose of 120 mg directly and by way of IV route in 10 min time; blood samples from peripheral and pulmonary sources were drawn at regular intervals between the 10 min period and the 8th hr; parenchymal samples were collected 1 and 2 hrs after drug administration. After separation of residual blood by centrifugation at high speed, the tissues are grinded and homogenized. The assay was performed with an immunological method using a fluorescent polarized detection system. Tissue levels were low in all the patients (0.5 to 2.75 micrograms/g of fresh tissue) and this in spite of the high level of blood collected throughout the administration protocol. As a rule, the relation between tissue/blood is lower than those discussed in literature concerning bronchial secretion. Beside this, the concentrations are similar in peripheral and pulmonary blood collected. Practical conclusions are drawn for therapeutic purpose.

Gentamicins↗

[Pharmacokinetics of gentamicin in the decompensed alcoholic cirrhotic patient. Therapeutic consequences].

Aminoglycosides and in particular gentamicin are still largely used in the treatment of spontaneous bacterial peritonitis in the decompensed alcoholic cirrhotic patient. For that matter, we decided to study the various passage of gentamicin in the ascites after its administration through IM injection (80 mg in 6 patients and 120 mg in 6 other patients) and through IV injection (120 mg in 6 other patients). What could possibly be the best protocol to replace the daily intraperitoneal injections? We found out that no matter what the style of injection is, the peritoneal levels are only exceptionnaly higher than 3 mg/g at the highest peak period. These results brought us to analyze the passage of gentamicin in the blood when injected intraperitonealy (160 mg in 6 patients), and then to propose a therapeutic protocol combining on the first day, to the peritoneal injection a loading dose of an IP injection of 160 mg, the relay been taken over later with a peritoneal injection of 80 or 120 mg repeated 2 or 3 times daily. For each of the protocol the pharmacokinetic coefficients of gentamicin were calculated.

Bacterial Infections↗

In vivo ageing of rat erythrocytes and cell surface labeling by D-galactose oxidase and sodium borotritide.

1. Young and old rat erythrocytes, separated in vitro, according to their age in vivo, were radioactively labeled at the cell surface D-galactosyl and 2-acetamido-2-deoxy-D-galactose (Gal and GalNAC) residues by treatment with D-galactose oxidase, followed by reduction with sodium borotritide: 2. The number of labeled surface residues per erythrocyte was found to be 0.52 X 10(6) +/- 0.08 X 10(6) for young, 0.38 X 10(6) +/- 0.05 X 10(6) for middle-aged and 0.32 X 10(6) +/- 0.05 X 10(6) for old, indicating a significant decrease of these surface Gal and GalNAC residues during ageing. 3. Qualitative changes were observed between the sodium dodecyl sulfate electrophoretic patterns of young, middle-aged and old labeled erythrocytes. 4. Quantitative changes were previously observed between the electrophoretic patterns of the labeled glycoproteins from young, middle-aged and old human labeled erythrocytes. 5. It is concluded that some of the changes occurring during in vivo ageing of rat and of human erythrocytes are different.

Animals↗