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H Choisy

Publications and source records attributed to H Choisy.

At least 37 records · Page 2Linked to original sources

[Role of sodium in the control of compartmental distribution of water during hemodialysis. I. Measurement of water transfer].

Symptomatic hypotension and other symptoms of the so-called dialytic desiquilibrium syndrome have been related to alterations of body fluid osmolality and distribution. Fluid removal from the intracellular compartment can be achieved by manipulating the sodium dialysate (NaD). The extracellular fluid volume ( EFCV ) was measured with inulin and/or 35SO = 4. Total body water changes were calculated in terms of fluid substraction induced by dialysis. They were monitored in 12 patients on hemodialysis with a highly permeable membrane and a careful monitoring of ultrafiltration. NaD was maintained constant throughout the session and was comprised between 140 and 170 mmol/l. Below 150 mmol/l NaD, ECFV was reduced more than the weight loss, indicating concomitant intracellular water loading. Conversely, over 150 mmol/l NaD weight loss resulted from extracellular and cellular water. We conclude: 1) transcellular water shift during dialysis is dependent of sodium dialysate; 2) net cellular water-shift was obtained for NaD higher than 150 mmol/l; 3) at least two compartments for water distribution should be taken into account for sodium modeling.

Body Water↗

Pharmacokinetic study of two pharmaceutical preparations containing alkaloid vincamine administered orally to human subjects.

In a crossover study of six healthy volunteers the pharmacokinetics and the bioavailability of vincamine were studied after administration of two oral forms. All subjects received an oral dose of 60 mg vincamine. The plasma concentrations of the drug were determined by a specific and sensitive gas chromatographic method. In this kind of subject the drug generally follows a one-compartment kinetic model. The average value of Tmax is 1.4 +/- 0.5 h-1 with the tablets and 1 +/- 0.6 h-1 with the solution; the Cmax are, respectively, 155 +/- 82 micrograms . 1(-1) and 133 +/- 104 micrograms . 1(-1). The AUC are 443 +/- 156 micrograms . 1(-1) h with the tablets and 315 +/- 178 micrograms . 1(-1) h with the solution. The short elimination phases, 1.43 +/- 0.80 h with the tablets and 1.55 +/- 0.78 h with the solution should be taken into account during chronic administration.

Administration, Oral↗

[Hypolipidaemic agents (author's transl)].

Since clofibrate was discovered, a number of compounds have been made available for the treatment of hyperlipoproteinaemias. Their principal pharmacological and therapeutic properties are summarized in this paper. Other compounds are now under pre-clinical or clinical studies, including probucol which is reviewed in this issue.

Animals↗

[Experimental pharmacology of probucol (author's transl)].

The experimental studies carried out so far have uniformly demonstrated that probucol lowers plasma cholesterol levels in all animal species. The drug has low toxicity and has been well tolerated during long-term treatment (up to 8 years in monkeys) in most species. In some dogs, however, probucol seemed to increase myocardial sensitivity to catecholamins, but this has not been found in other species. The pharmacokinetics of probucol show a rather slow turnover and are characterized by storage of the drug in adipose tissues, which may explain why the hypocholesterolaemic effect is progressively obtained. The main channel of excretion is the bile. No other pharmacological action has been described with probucol, which in the present state of knowledge appears to be a predominantly cholesterol-lowering agent.

Adipose Tissue↗

[The acetylator polymorphism in a Khmer population: clinical consequences].

The great variability of slow acetylator (SA) and/or rapid acetylator (RA) frequency is mainly due to ethnic-racial origin. Using the urinary elimination ratio of three metabolites of caffeine--acetylamino formylamino methyluracil (AFMU) to AFMU + 1-methyl urate (1U) + 1-methyl xanthine (1X)--we settled the acetylation phenotype in 54 independent subjects of Khmer and 70 independent subjects of Caucasian origin. Using DNA from peripheral leucocytes, we determined by PCR, in 32 Khmer and 122 Caucasian subjects, the frequencies of wild-type alleles (NAT-2 *4) and of mutated alleles (NAT-2 *5A, *6A, *7A). The frequency of SA was respectively 28 per cent and 61 per cent in Khmer and Caucasian subjects. The antimode of the distribution of the ratio was different in the two populations: 0.07 in Khmers and 0.18 in Caucasians showing a reduced acetylation capacity in the Khmer population in spite of a higher frequency of RA. The frequencies of alleles were also different between the two populations. Between Khmers and Caucasians respectively: *4: 48.4-23.8 per cent *5A: 15.6-44.2 per cent. *6A: 29.7-32.0 per cent. *7A: 6.3-0 per cent. These differences might be taken into account to define a therapeutic strategy in the treatment of tuberculosis by isoniazide.

Acetylation↗

The effects of 5-fluorouracil on contractility and oxygen uptake of the isolated perfused rat heart.

Clinical cardiotoxicity related to 5-fluorouracil (5-FU) simulates either myocardial ischemia or left ventricular dysfunction. In order to characterize the changes occurring in the heart following 5-FU administration, the isovolumic perfused rat heart model according to Langendorff has been used. Particular emphasis was laid on contractility and oxygen uptake. Perfusion of isolated hearts with 1 mg/L 5-FU for 80 minutes failed to show any differences in contractility and oxygen consumption in comparison with the control group. On the contrary, 5-FU pretreatment of Wistar rats (50 mg/kg I.P. for 5 consecutive days) led to a decrease in inotropism without any change in maximum relaxation rate. The most significant finding was the consistent increase in oxygen consumption throughout the 80 minutes of perfusion (p less than 0.05) associated with a decrease in the fractional extraction of oxygen. Mean coronary flow was consistently increased in the 5-FU-pretreated group. Lactate release and CK Leakage did not differ in the two groups. In the 5-FU-pretreated group the ratio of oxygen consumption to rate-pressure product remained significantly elevated throughout 80 minutes of perfusion in comparison with the control group (p less than 0.05). Inappropriately high oxygen uptake could be a reflection of cellular metabolic disturbances responsible for post-ischemic dysfunction.

Animals↗

Combination chemotherapy with cisplatin, etoposide and gallium chloride for lung cancer: individual adaptation of doses.

Twelve inoperable lung cancer patients were treated with a combination chemotherapy of cisplatinum (CDDP) and etoposide (VP16), as a continuous infusion for 5 days, every 21 days, and with a daily oral administration of GaCl3. Dosages of CDDP and VP16 were adapted in order to obtain an area under the curve (AUC) of 80,000 micrograms l-1.h for plasma total platinum and of 200 mumol.l-1 h for plasma VP16 during each 120 h infusion. GaCl3 was given at the dosage of 400 mg/24h from the time of diagnosis at least until the evaluation after 3 courses of chemotherapy. An objective response was observed in 5 non small cell (NSCLC) lung cancer patients (group 1) and 3 small cell (SCLC) lung cancer patients (group 2). In the other 4 patients with a NSCLC no partial response was noted (group 3). No significant difference in area under the curve (AUC) was noted between the 3 groups, either for plasma total platinum (group 1 = 89,598 +/- 20,843 micrograms l-1.h; group 2 = 88,081 +/- 15,431 micrograms l-1.h; group 3 = 83,820 +/- 13,455 micrograms l-1.h), or for VP16 (group 1 = 227 +/- 41 mumol.l-1 h; group 2 = 217 +/- 29 mumol.l-1.h and group 3 = 211 +/- 30 mumol.l-1.h). The maximal plasma Ga concentrations were 244 +/- 34 micrograms/l in group 1, 112 +/- 57 micrograms/l in group 3 (p less than 0.005) and 243 +/- 132 micrograms/l in group 2. It was then decided to increase the dose of GaCl3 in the further non-responding patients. In 6 responders, 3 additional courses of this combination chemotherapy could have been given without major toxicity, allowing a much more important decrease in the tumor volume in 4 of them. This schedule of treatment should permit the chemotherapy to continue for longer than 6 courses, in order to improve the survival time.

Adenocarcinoma↗

[Chronopharmacokinetics of dexamethasone in young subjects].

Dexamethasone chronopharmacokinetics was studied in six young subjects 20 to 30 years old. The randomized cross-over study consisted of evening (11.00 p.m.) or morning (08.00 a.m.) dose separated by a period of one week. After the evening administration of the drug, only Tmax (1.77 +/- 0.74 à 11.00 p.m. and 0.99 +/- 0.64 à 08.00 a.m.) and Cmax/Tmax were higher than those determined at 08.00 a.m. This difference might be related to a cyclic variation of the absorption phase of dexamethasone. Thus, in our study, the time of administration has only a weak effect on the pharmacokinetics of dexamethasone.

Adult↗