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Biomedical subjects

J Fabre

Publications and source records attributed to J Fabre.

At least 109 records · Page 6Linked to original sources
PubMed1983

The genetic control of drug oxidation in the liver.

Hepatic drug oxidation is a major source of interindividual variations in drug behaviour. A wide spread of the pharmacokinetic parameters of extensively oxidized drugs is a common observation. For such compounds, in the absence of polymodal distribution of the kinetic parameters, no distinct genetic influence can be detected. The discovery that the urinary excretion of debrisoquine and its main hydroxylated metabolite displays a bimodal pattern opened a new field in the study of hepatic metabolism. This new genetic polymorphism now concerns the oxidative metabolism of numerous substances such as antihypertensive agents, antidepressants, antiarrhythmic drugs and various other unrelated compounds. The poor metabolizer phenotype is observed in some 8% of individuals in European populations. We have shown that the oxidative metabolism of beta-adrenoceptor blocking drugs is under the same genetic control as debrisoquine. Using bufuralol as a test drug, we have studied the influence of polymorphic oxidation on interindividual variations of parent drug and metabolite plasma concentrations. It appears clearly that oxidation polymorphism is a major factor of variability in hepatic drug handling. This fact has important clinical and pharmaceutical implications.

Adrenergic beta-Antagonists↗
PubMed1983

Consequences of renal insufficiency on the hepatic clearance of some drugs.

There have been numerous investigations into the effect of kidney or liver diseases on the renal or hepatic elimination of drugs, but little is known about the possible consequences of renal insufficiency on the hepatic clearance of medicinal agents. The first reports of diminished presystemic elimination of drugs in renal failure were presented by Bianchetti in 1976 for propranolol and by Levy in 1979 for dextropropoxyphene. We confirmed the fact that the hepatic presystemic elimination of drugs might be diminished by kidney diseases. We studied this phenomenon with the beta-blocking agents tolamolol, bufuralol and oxprenolol. Tolamolol is eliminated from the body mainly by aromatic hydroxylation and, for bufuralol, aliphatic hydroxylation also plays an important role, whereas, for oxprenolol, glucuroconjugation of the unchanged compound is an important route of elimination. After oral administration, the areas under the plasma/blood concentration curves were markedly increased in patients with renal insufficiency as compared to healthy subjects. The clearance approach of Rowland and Tozer led to the conclusion that decrease of the presystemic hepatic elimination might be the main reason for this finding. Cefoperazone is a cephalosporin eliminated to 75% by the biliary route under normal conditions. In a study in which the drug was intravenously infused to both healthy volunteers and patients with renal insufficiency, we found that in some patients the extrarenal clearance was markedly reduced. It is probable that in this situation the patients also suffered from a slight hepatic insufficiency, as sometimes observed in the case of kidney disease associated with a poor physical condition. It is well-known that in patients with terminal liver failure, the kidney may also be involved, producing a condition known as the "hepato-renal" syndrome. We feel that there is evidence to support the hypothesis that renal failure can disturb the pharmacokinetics of drugs by processes other than merely reducing their renal excretion. The precise causes of the decreased hepatic elimination found in renal patients remains, however, to be determined.

Adrenergic beta-Antagonists↗
PubMed1983

[Borderline hypertension. Survey of 8390 international officials].

The epidemiology of borderline hypertension (BHT) is studied on a population comprising 8390 international civil servants. The prevalence of BHT (systolic 141-159 mm Hg and/or diastolic 86-94 mm Hg) is noted to be 21,4%. It affects men and obese more frequently and increases with age. It differs according to national origin (p less than 0.001), being least frequent for Indians (9%) and most frequent in black Africans (38%). Professional status does not play a role. The occurrence of true hypertension is noted in 43% and 54% of those who were followed over a period of 15 resp. 20 years after discovery of BHT (as opposed to 22% for the entire population of the same age, p less than 0.01). The occurrence of sustained hypertension is more likely when there is both systolic and diastolic BHT, in certain predisposed national groups, in men and possibly also when there is obesity. Even when BHT does not change into sustained hypertension, the risk of cardio-vascular morbidity is increased 2.5 times. These findings give rise to series of practical considerations.

Adult↗
PubMed1982

[Use of drugs in a medical polyclinic].

The medical prescriptions of 18 house officers working at the Policlinique Universitaire de Médecine in Geneva were analyzed for a period of 17 working days and provide insight into drug therapy chosen for 2194 outpatients at 2694 consultations. These patients were prescribed an average of 1.39 drugs each or 1.13 per call. Of the 298 different drugs thus prescribed, the following were chosen most frequently (in decreasing order): Digoxin, Hygroton, Lexotanil, Metamucil, Voltaren, Aspirin, different insulins and Aldomet. Antimicrobial agents accounted for only 2.5% of all prescriptions, while vitamins and "fortifiers" represent an even lower percentage. It would be possible to limit the number of drugs, since half of the prescriptions cover 23 drugs and 90% of all prescriptions cover 119 drugs. Prescription patterns vary markedly from one subspecialty of internal medicine to another, but also between physicians working in the same field. House officers in charge of given sectors of the city (internists not working in a subspecialty) may thus prescribe between 1,83 and 2.9 drugs per patient, whereas the number of drugs chosen may vary between 81 and 134. Some quaint individual preferences for drugs were also noted and the trend is analyzed. The data is compared with results of the few existing similar studies and offers food for thought on prescription habits, directed ultimately towards a more rational approach to drug therapy for outpatients.

Ambulatory Care↗
PubMed1982

[Pharmacokinetic study of a cephalosporin: cefoperazone in patients with a Kehr drain].

Cefoperazone is a semi-synthetic cefalosporine for parenteral use which has an excellent activity against a wide range of grampositive and gramnegative bacteria, especially Pseudomonas aeruginosa, Enterobacter, Proteus indole positive and Serratia marcescens. The pharmacokinetics of the new antibiotic have been studied in patients who had undergone cholecystectomy and choledochotomy for lithiasis and who required T-tube drainage of the bile duct. Five patients were anicteric and one was icteric. Mean serum concentration of cefoperazone determined by a microbiological method) measured after a two-hour intravenous perfusion of 2 g cefoperazone was 198.6 microgram/lm; this level is higher than the mean level measured in normal subjects (134 microgram/ml) but lower than the mean level measured in patients with hepatic insufficiency (208 microgram/ml). Apparent half life of elimination was longer (mean 4.1 hours) in the patients than in controls (mean 1.6 hours) and compares with that of patients with hepatic insufficiency (mean 4.3 hours). The distribution volume and renal clearance are similar to that in healthy volunteers and patients with hepatic insufficiency. Extrarenal clearance of cefoperazone was significantly lower in our patients (15.8 ml/min), as it is in patients with hepatic insufficiency (7.3 ml/min), than in the control group (59.4) ml/min). Cefoperazone concentrations in the bile were 10-20 times higher than those in the serum; in the icteric patient the concentrations achieved were still higher than the MIC values for organisms commonly encountered in the bile. These results open the way to the use of cefoperazone to treat infectious biliary diseases, particularly angiocholitis, which need a high biliary antibiotic concentration.

Adult↗
PubMed1982

The infusion of catecholamines in dogs under general anaesthesia with fentanyl. The effects on intrapulmonary shunt.

The pulmonary venous admixture, PaO2, and pulmonary and systemic haemodynamics were studied in six mongrel dogs during infusion of dobutamine (infusion rate 7.5 micrograms . kg-1 . min-1), dopamine (7.5 micrograms . kg-1 . min-1) and isoproterenol (0.1 microgram . kg-1 . min-1). Anaesthesia was performed by a single injection of Fentanyl (0.35 mg/kg). The carbon dioxide tension and body temperature were strictly maintained within limits. Only isoproterenol produced a significant change in pulmonary arterial pressure from an average of 1.2 +/- 0.4 kPa to 1.6 +/- 0.2 kPa (P less 0.05). There was no significant change in systemic haemodynamics with any of the three drugs. The use of catecholamines in dogs with healthy lungs does not induce any development in pulmonary venous admixture when haemodynamics are unchanged. Changes in these variables are dependent upon changes in pulmonary blood flow rather than being direct effects of the catecholamine.

Anesthesia, General↗
PubMed1982

Warthin-Finkeldey-like cells in benign and malignant lymphoid proliferations.

Multinucleate giant cells resembling Warthin-Finkeldey cells have been described in various lymphoid disorders. These Warthin-Finkeldey-like cells (WFLC) with as many as 50 nuclei are of three main types: reticular, lymphocyte and intermediary. In reactive lymphoid proliferations (34 cases) WFLC were mainly observed inside germinal centres and to a lesser extent in the interfollicular zones. In neoplastic lymphoid proliferations (33 cases) WFLC were most commonly found in the lymphocytic predominance type of Hodgkin's disease (16/25 cases). All non-Hodgkin's lymphomas (13 cases) in which WFLC were detected proved to be of low grade malignancy (lymphocytic: one case, lymphoplasmacytic-plasmacytoid: six cases; and centroblastic-centrocytic, six cases). They were also found in two cases of angioimmunoblastic lymphadenopathy. Immunoperoxidase and electron microscopic studies could not elucidate the exact histogenesis of these cells, but it is assumed that they are associated with B cell proliferations.

Hodgkin Disease↗
PubMed1981

[Retention of metabolites of a beta-blocking drug, oxprenolol, in renal insufficiency].

The pharmacokinetics in blood of oxprenolol and its glucuro-conjugated metabolites has been investigated in healthy volunteers and hemodialyzed patients; in addition, the effect of the drug on the heart rate has been measured. Renal insufficiency does not modify the elimination kinetics of oxprenolol, but it does lead to massive retention of the glucuro-conjugated derivatives on multiple dosing. The present study failed to show hydrolysis of the conjugates with liberation of the active parent compound. In addition, from measurement of the exercise-stimulated heart rate it can be concluded that active metabolites of oxprenolol are absent. The duration and intensity of the effect of a single dose of the drug were comparable in the healthy volunteers and the patients with renal insufficiency.

Biotransformation↗
PubMed1981

[Poisoning by adulterated edible oil].

In spring 1981, thousands of people living in Madrid were intoxicated by adulterated edible oil containing oleoanilide and probably other toxic substances. Due to increasing international travel Swiss doctors may also be faced with this particular disease. The case is reported of a 28-year-old woman who presented in May 1981 with a highly febrile influenza-like syndrome after consuming the adulterated oil while in Madrid. In the following weeks she developed myopathy, characterized by muscular weakness and pain, aldolase elevation and typical electromyographic disturbances, as well as edema and general discomfort. The white cell count showed eosinophilia up to 2170/mm3. Five months later, the symptoms are still continuing. Other members of the family have been exposed to the oleoanilide and exhibited various abnormalities which constitute a new clinical syndrome different from previously reported intoxications by industrial oil.

Acetanilides↗