Search PubMed⌕ Search

Biomedical subjects

J Fabre

Publications and source records attributed to J Fabre.

At least 199 records · Page 11Linked to original sources
PubMed1976

Renal failure, drug pharmacokinetics and drug action.

Patients with renal insufficiency often react abnormally to a number of drugs. Small doses that are safe under normal conditions may cause severe and even fatal side-effects. As a consequence, modification of the usual drug dosage of these drugs in required in renal insufficiency. Since the risk of retention concerns only those drugs which are mainly excreted by the kidney, it is possible to establish a mathematical relationship between glomerular filtration rate and the rate of drug elimination. These relationships serve as a basis for the determination of the proper dosage regimen for the individual patient. Such dosage adaptation for intermitten drug administration can be obtained by two methods and a series of compromises between them: (1) increase of the dosage interval without changing the dose, and (2) reduction of the does without changing the frequency of administration. One must however, not only consider inadequate drug elimination but also a number of other factors. Some of these modify the behaviour of the drug, such as hypoalbumineamia, which causes an increase of the unbound portion of the drug; anomalies of the volume of distribution, as found in patients with oedema; metabolic disturbance; alteration of absorption from the gastro-intestinal tract, etc. Other factors are related only indirectly to the pharmacokinetic behaviour of the drug. Frequently, there is an increased sensitivity to the undesirable side-effects of certain drugs in patients with renal insufficiency, causing the level of tolerance to be lowered compared with normal patients. Such an effect probably involves functional or morphological modifications of the drug receptors, or interaction with substance retained in renal insufficiency. Furthermore, drugs may accentuate the consequences of the nephropathy or have increased nephrotoxicity for those with diseased kidneys. It is with these important reservations that a critical analysis of the proposed methods of adapting drug dosage in renal insufficiency is presented. An appendix tabulates the effects of renal insufficiency on the behaviour of 117 drugs. Irrespective of the method used to calculate drug dosage, all patients with renal disease must be monitored closely, particularly for signs of unexpected drug toxicity.

Drug Administration Schedule↗
PubMed1975

[Proceedings: Alkaline phosphatases in patients in chronic hemodialysis].

The alkaline phosphatases (AP) have been studied in 28 patients on chronic hemodialysis. Total AP averaged 49 IU/1 while 4 out of the 28 patients exhibited pathologic values (above 60 IU/1). Determination of iso-AP by acrylamide gel electrophoresis revealed the existence of an intestinal band in 50% of cases, thought this is not observable in a control population. The only relationship seen between the presence of the intestinal iso-AP and different parameters concerned the blood groups O and B. Significant increase of total AP is in all cases due to a bone iso-AP. During a hemodialysis session a mean increase of 30% in total AP has been noted. An increase in total AP is observed in only 2 cases out of 17.

Alkaline Phosphatase↗
PubMed1975

[Proteinuria in mature diabetic patients. Quantitative and qualitative analysis].

Proteinuria has been analysed in 334 maturity-onset diabetics and 80 matched controls. Proteinuria measured in the recumbent position exceeded 100 mug/min in 53% of the diabetic population. The percentage of excessive proteinuria increased with duration of the disease. Sex and age had no influence. Out of 55 first year diabetics, 49% had abnormal quantitative proteinuria; this is in contrast to 76 longterm diabetics (over 12 years) of whom 38% had proteinuria under 100 mug/min. Electrophoresis and immuno-electrophoresis showed a glomerular pattern in 40%, a tubular pattern in 15% and a mixed pattern in 8% of all the diabetics. 32% of the diabetics with quantitatively normal proteinuria were abnormal qualitatively, and this may be the first manifestation of diabetic nephropathy. Thirty-eight other patients had a normal electrophoretic pattern in spite of increased proteinuria. Proteinuria levels were significantly associated with hematuria, bacteriuria and reduced GFR, but not with leukocyturia, insulin dependence and hypertension. Upright position increased the proteinuria to a greater degree amongst the patients with normal proteinuria. We discuss the role of increased filtration pressure and glomerular permeability in modifying proteinuria in diabetes. Sensitive quantitative and qualitative proteinuria determinations are important tools both in early diagnosis of diabetic nephropathy in clinical practice and in epidemiological studies.

Adult↗
PubMed1975

[Alkaline phosphatase isoenzymes. Selection of the seperation methods and their diagnostic value].

Polyacrylamide gel electrophoresis (PAGE) of alkaline phosphatase (AP) was performed in 116 patients with elevated AP and in 36 controls. Results were compared with clinical data and with the heat inactivation techniques for AP isoenzyme separation. This latter method is simple but approximate; it is without value in the case of coexistent bone and liver pathology. PAGE gave a clear separation of liver, bile, bone, and intestinal AP isoenzymes. Disagreement with clinical data was rare (6 out of 86) and occurred in cases of associated bone and liver pathology (with 1 exception only), where one of these two abnormalities was not detected. Heat inactivation is useful as a screening test. If the cause of the elevated AP remains unknown after a few simple examinations, PAGE should then be utilized. Although more time-consuming, it is certainly more effective in the separation of AP isoenzymes.

Adult↗
PubMed1975

[Physiological proteinuria. Data of acrylamide-SDS gel electrophoresis and other methods of qualitative and quantitative analysis].

Since detection of the first stage of nephropathies requires an exact definition of physiological proteinuria, this has been sought in 97 healthy individuals. Measured by a modification of the biuret reaction, physiological proteinuria did not exceed 100 mug/min in the recumbent position (average of 24.5 mug/min) and 150 mg/24 h (average of 51 mg/24 h). No significant differences were seen with respect to age or sex. Qualitative analysis of urinary proteins was done by cellulose acetate electrophoresis, immunoelectrophoresis and polyacrylamide-SDS electrophoresis. This latter method has the great advantage of classifying the proteins according to their molecular weight, wtihout electrostatic interference. Its graphic representation delineates a normal zone allowing an objective distinction between physiological and pathological proteinurias. In the majority of cases, the proportion of albumin is between 25 and 55%. The orthostatic position increases proteinuria (average of 41 mug/min) with a tendency to a distribution which erroneously suggests a glomerulopathy. Accordingly, investigation for small changes in proteinuria should always be carried out on urine formed in the recumbent position.

Adult↗
PubMed1975

[Factors of arterial and renal complications in diabetes].

In a population of 744 diabetics composed mainly of elderly female patients, 172 developed hypertension after the onset of diabetes. Compared to normotensive diabetics, they had an increased prevalence of diabetic retinopathy (p less than 0.001), cerebral accidents, ischemic disorders of the lower limbs and a decreased glomerular filtration rate (p less than 0.05); they are frequently insulin-dependent and difficult to manage. In 173 other indivuals the diabetes emerged several years after the hypertension. This group was characterized by relatively easily controlled blood sugar and increased prevalence of angina and myocardial infarction (p less than 0.001). The association of hypercholesteremia with hypertension increases the risk of coronary disease (p less than 0.02) and, to a lesser degree, of glomerular insufficiency. The prevalence of coronary symptoms increases with obesity (p less than 0.05) while retinopathy increases with insulin dependence (p less than 0.001). From this information it may be concluded that the importance of various risk factors in the diabetic chiefly varies according to the vascular territory involved: cerebral vascular accidents occur mainly in hypertensives, while the presence of retinopathies, proteinuria and peripheral ischemia is directly related to the diabetes and particularly to insulin dependence. The risk of coronary lesions increases considerably when hypertension is added to the diabetes, with an even greater risk in the case of a diabetic, hypertensive, hypercholesterolemic nexus.

Aged↗
PubMed1975

Comparison of the pharmacokinetics of glipizide and glibenclamide in man.

Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-lives increased steadily with time. The two sulfonylureas were extensively metabolized and were excreted in the urine as hydroxylated or conjugated metabolites. The effects of both drugs on blood glucose and immunoreactive insulin were comparable. The findings are compared with other published results.

Administration, Oral↗
PubMed1975

Behaviour of doxycycline in the tissues.

Little is known about the behaviour of antibiotics in the tissues. To investigate this problem, rats were sacrificed in groups of six, 1, 2, 4, 6, 8, 12 and 18 h after an intraperitoneal injection of 10 mg doxycycline/kg body weight. The antibiotic levels were determined in the nine major organs and in the serum by a microbiological method. One hour after injection, the doxycycline concentrations in all the tissues were already higher than the serum concentrations. After 4 h, the concentration exceeded 2.5 mug/ml in the lungs, muscles, testes and heart, and were much greater in the excretory organs: 11.4 +/- 4.1 mug/ml in the liver, 10.2 +/- 1.6 in the renal medulla and 27.8 +/- 7.0 in the renal cortex. Throughout the experiment, the lung and muscle concentrations were about double the serum concentrations, and this occurred with great regularity. Doxycycline is thus capable of penetrating extremely rapidly and intensely into tissues, while still retaining a great degree of freedom of movement between plasma and tissues.

Animals↗
PubMed1975

[Muscular work and its hyperemic phase in the patient with arteritis].

Already users of a method of functional assessment of the muscular circulation in the patients with peripheral artery disease by Xenon 133, the authors propose a radical modification of the performance of the exercise test. A quantified exercise test leads to a new and more objective interpretation of the radio-active tracer elimination curve. This new method permits the measurement of the total quantity of blood which passed during the hyperhaemic stage and its time distribution. The aim of this test is to form an opinion on the tenacity and the efficiency of the supplementary mechanisms when there is an occlusion of the arterial axis.

Adult↗