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Biomedical subjects

M Laville

Publications and source records attributed to M Laville.

At least 163 records · Page 9Linked to original sources

Stress-induced renal functional alterations in normotensives.

This study was performed to assess changes in renal function accompanying cardiovascular responses to mental stress. Glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), filtration fraction (FF), sodium excretion, and segmental sodium tubular reabsorption (lithium clearance) were measured in 15 normal volunteers during rest and stress. The psychological stress test used is based on a computerized version of the Stroop word color conflict test. Stress induced a significant (P less than .05) and sustained increase in blood pressure and heart rate. During stress, GFR and RPF did not change whereas FF increased significantly (P less than .05) and sodium excretion tended to decrease. The decrease in sodium excretion was due to a significant (P less than .05) increase in proximal reabsorption, which may be mediated by renal hemodynamic changes. The observed significant increase in FF suggests an increase in postglomerular arteriolar resistances, which may account for the increase in proximal sodium reabsorption through an alteration in peritubular Starling forces. In the long run, the stress-associated increase in sodium reabsorption may contribute to the development of hypertension.

Adult↗

Lipolytic and ketogenic fluxes in human hyperthyroidism.

The effect of hyperthyroidism on lipolytic and ketogenic fluxes was determined by measuring simultaneously (stable isotope methodology) glycerol, nonesterified fatty acids (NEFA), and ketone body (KB) kinetics in euthyroid and hyperthyroid subjects. In the postabsorptive state hyperthyroid patients had normal concentrations of insulin and glucagon, but increased concentrations (P less than 0.01) and turnover rates (P less than 0.01) of glycerol, NEFA, and KB. The ratio of NEFA appearance rate to glycerol appearance rate was decreased in hyperthyroid subjects (2.34 +/- 0.23 vs. 3.15 +/- 0.22; P less than 0.05), indicating that intracellular cycling between triglycerides and fatty acids was increased. The percentage of NEFA flux used for KB production, calculated from NEFA disappearance rates and KB appearance rates, was increased in hyperthyroid patients (21.20 +/- 2.75% vs. 13.37 +/- 0.63%; P less than 0.05), suggesting a diversion during hyperthyroidism of hepatic fatty acid metabolism toward ketogenesis. However, when the plasma NEFA levels of control subjects were raised by the infusion of a triglyceride emulsion to levels comparable to those observed in hyperthyroid patients their percentage of NEFA flux used for ketogenesis rose to values slightly higher (26.30%) than those of hyperthyroid subjects. In conclusion, 1) hyperthyroidism results not only in increased lipolysis, but also in enhanced triglyceride-fatty acid cycling, which could contribute to the excessive energy expenditure; and 2) the increased KB production of hyperthyroid patients results more from an increase in NEFA availability than from a direct stimulation of hepatic ketogenesis.

Adult↗

[New techniques for investigation of human nutrition].

Accurate determination of energy requirement and nutrients metabolism is essential to improve physiological knowledge and for physiopathological purpose in human nutrition. This evaluation is an absolute necessity for food industry. Energy expenditure could be precisely determined by indirect calorimetry or doubly labeled water technic. Nutrients metabolism (kinetics?) and substrates turn-over studies are now accessible without health hazard using tracers labelled with stable isotopes. These three methods are the basic tools for the new Research Nutrition Center which are now in progress.

Calorimetry, Indirect↗

Pharmacokinetics of oral cefatrizine in patients with impaired renal function.

The pharmacokinetics of cefatrizine was studied in 15 patients with various degrees of renal impairment, after single oral administration of 500 mg. Cefatrizine elimination was reduced in parallel to renal function, as indicated by the significant correlations between apparent clearance (Cl/F) and creatinine clearance (Clcr), and between renal clearance (Clr) and creatinine clearance (Clcr). In patients with totally impaired renal function, the residual clearance (Cl/F) was 63 ml.min-1 per 1.73 m2. Comparisons with previously published data indicate that the apparent volume of distribution (V/F) of cefatrizine was lower in patients with impaired renal function than in young healthy volunteers, leading to increased peak concentrations (Cmax), but there was no relationship between V/F and Clcr. In patients with totally impaired renal function, the upper limit of cefatrizine elimination half-life was estimated to 5.5 h. The clinical significance of pharmacokinetic modifications observed in renal disease patients may only be realized through integration of pharmacodynamic characteristics of cefatrizine. The observed increase in Cmax and the lengthening of t1/2 could suggest a reduction of dosing frequency in patients with severe renal impairment.

Administration, Oral↗

[Renal function during stress in hypertensive patients].

In this study, the measurement of blood pressure values, glomerular filtration rate (GFR, inulin clearance), renal plasma flow (RPF, PAH clearance), the filtration fraction (GFR/RPF), natiuresis and proximal sodium resorption (measured by lithium clearance), was performed at rest and during a computerised psychological stress test (Stroop word color conflict test) in 12 normotensive and 10 hypertensive subjects. The stress induced in the normotensives induced a significant increase of the filtration fraction and proximal tubule sodium resorption. The hypertensive kidney, submitted to a basal vasoconstriction greater than that of the normotensive kidney, does not react to stress. In the hypertensives, proximal sodium resorption occurs but is not significantly greater than at rest. In the long-term, the increased sodium resorption during stress could contribute to the development and the persistence of essential hypertension.

Adult↗

Use of a new gas chromatograph isotope ratio mass spectrometer to trace exogenous 13C labelled glucose at a very low level of enrichment in man.

The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4 +/- 0.7 mg.kg-1.min-1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1 +/- 1.1 mg.kg-1.min-1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g.kg.-1,1 g.kg.-1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97 +/- 0.04 g.kg.-1 and 1.2 +/- 0.04 g.kg.-1, exogenous glucose appearance was 0.51 +/- 0.02 g.kg.-1 and 0.84 +/- 0.04 g.kg.-1, endogenous glucose production was 0.44 +/- 0.04 g.kg.-1 and 0.35 +/- 0.06 g.kg.-1 after the 0.5 and 1 g.kg.-1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of thyroid hormones on gluconeogenesis from glycerol in rat hepatocytes: a dose-response study.

The role of L-3,3'-5 triiodothyronine (T3), in a pathophysiological range, on gluconeogenesis from low concentration of glycerol (2 mmol/L), was investigated in isolated liver cells from 24-hour fasted rats either thyroidectomized, normal, or treated by a T3 dose ranging from 1, 5, or 10 micrograms/d/100 g body weight (BW) during 3 days to 50 micrograms during 7 days. Gluconeogenesis from glycerol was decreased by 63% in hypothyroid rats and increased by 35% in severely hyperthyroid rats. However, in cells from mild hyperthyroid rats no increase of gluconeogenesis was observed. Nevertheless, in mild hyperthyroidism, alpha-glycerophosphate (G3P) was significantly decreased and gluconeogenesis from glycerol was not inhibited by the addition of ethanol (10 mmol/L), both of which have a drastic effect in cells from thyroidectomized rats. The decrease of gluconeogenesis observed in cells from thyroidectomized rats was reversed by the addition of pyruvate (10 mmol/L). Thus, when the cells were in a "reduced state" (addition of ethanol) the differences between the group were magnified, and when the cells were in an "oxidized state" (addition of pyruvate) the differences were suppressed. These findings suggest that alteration of the capacity of reducing equivalents transfer from the cytoplasmic compartment to the mitochondria is the main mechanism by which mild hyperthyroidism can stimulate gluconeogenesis.

Animals↗

Cardiovascular reactivity to and renal impact of stress and exercise: effects of bisoprolol.

The orthosympathetic nervous system is involved in the pathogenesis of essential hypertension. In this study, we carried out tests of sympathetic stimulation using successfully an isometric exercise and a psychological stress. The efficacy of the two tests in 10 normotensive patients (NTs) was assessed by a significant increase in blood pressure and heart rate and a significant increase in metanephrine urinary excretion. These tests, repeated 2 months later, were perfectly reproducible in NTs. The cardiovascular response during exercise and stress was significantly higher in 10 hypertensive patients (HTs) than in NTs. At rest, urinary norepinephrine excretion was significantly higher in HTs. In contrast to NTs, stress in HTs significantly increased urinary excretion of epinephrine and norepinephrine, whereas exercise failed to increase urinary catecholamine excretion in both groups. In HTs, both tests induced an increase in microalbuminuria. Among functional renal parameters, only proximal sodium reabsorption (measured by lithium clearance) was significantly lower in HTs than in NTs, compensated by a higher distal reabsorption. In HTs, 2 months of treatment with bisoprolol reduced rest and peak heart rate and blood pressure, but failed to reduce blood pressure reactivity to the orthosympathetic stimulation. Proximal sodium reabsorption at rest was normalized by the treatment. Bisoprolol was also able to reduce microalbuminuria during the 24 h and in the rest period preceding the test, but the same percent increase was observed during tests.

Adrenergic beta-Antagonists↗

[Is it possible to use creatinine for following the development of renal insufficiency?].

Accurate methods of measuring glomerular filtration rate are usually considered as expansive and time consuming. Therefore, alternative methods (creatinine clearance, either calculated or measured, reciprocal plasma creatinine, slopes of creatinine vs time) have frequently been used to assess the rate of progression of renal failure and predict the time of dialysis. The present review underlines the limitations of such techniques frequently underestimated in recent trials intending to evaluate the potential benefit of protein restriction. It delimitates the restrictive conditions in which such methods could be used for clinical but not research purposes.

Creatinine↗

Cyclosporin A-sensitive nephrotic syndrome preceding Hodgkin's disease by 32 months.

A 20-year-old man developed a massive nephrotic syndrome, rapidly complicated by pulmonary embolism and septicemia. Two renal biopsies taken 3 months apart showed minimal change glomerulonephritis. Treatment with prednisolone 1.5 mg/kg/day failed to induce a sustained remission, then monotherapy with cyclosporin A (CsA, 5 mg/kg/day) was started. Complete remission was obtained after 15 weeks. CsA was gradually tapered to 3 mg/kg/day. Twenty-two months after starting CsA, a routine examination disclosed a right sub-clavicular lymph node, of which histological examination showed a class 4 large cell Hodgkin's lymphoma. CsA was abruptly withdrawn and a polychemotherapy resulted in lymphoma remission after four courses. Ten months later, Hodgkin's disease is currently in remission and there is no relapse of proteinuria.

Adult↗

[Side effects of therapeutic plasma exchange. A controlled prospective study].

Solutions of human albumin are generally used as plasma substitutes during therapeutic plasma exchanges. The safety of 2 solutions of human albumin was evaluated in a multicentre, randomized, double-blind trial. Between June, 1984 and February, 1986, 80 patients who were undergoing plasma exchanges for the first time entered the study and were randomly assigned into 2 groups according to whether they received plasma albumin (PM) or placental albumin (PC). Each patient had 6 plasma exchanges over a 2-week period. Failure was defined as the occurrence of an untoward effect during an exchange. No significant difference in the number of failures was found between the 2 albumins (PM 23/40, PC 15/40; P = 0.07). However, when the type of adverse reaction was taken into account there was a significant difference between the two treatment groups regarding the number of febrile episodes (PM 8, PC 2; P = 0.043) and shivering fits (PM 9, PC 2; P = 0.023). Thus, the nature of the albumin has no significant influence on the overall safety of plasma exchanges, but it seems that different methods of preparation may affect the type of untoward effect observed.

Adult↗

Potassium channel openers act through an activation of ATP-sensitive K+ channels in guinea-pig cardiac myocytes.

In a previous article (Escande et al. 1988a), we have shown that cromakalim (BRL 34915), a potassium channel opener (PCO), is a potent activator of ATP-sensitive K+ channels in cardiac cells. In the present article, the influence on K+ channels of two other potassium channel openers chemically unrelated to cromakalim, RP 49356 and pinacidil, has been investigated in patch-clamped isolated cardiac myocytes. In the whole-cell configuration, K+ currents were recorded in the presence of 50 microM TTX and 3 microM nitrendipine or 3 mM cobalt. Like cromakalim, RP 49356 or pinacidil activated a time-independent outward current at 33-35 degrees C but not at 19-21 degrees C, which showed little voltage-dependency in the potential range -60 to +60 mV. Its amplitude was a function of the agonist concentration, e.g. it was 2.1 +/- 0.4 nA at +60 mV with 30 microM RP 49356 and 4.3 +/- 0.8 nA with 300 microM. In control conditions, glibenclamide, a blocker of K+-ATP channels in pancreatic and heart cells, affected neither the inward rectifier, iK1, nor the delayed K+ current, iK. At 3 microM, glibenclamide fully prevented the effects of 300 microM RP 49356 or pinacidil. At lower concentrations, glibenclamide partially counteracted the activation by PCOs of a K+ current. In the cell-attached configuration, externally applied RP 49356 or pinacidil caused opening of large channels which reversed around O mV in a high K+ external medium. In inside-out patches, both RP 49356 or pinacidil activated K+-ATP channels by increasing the time period for which the channels remained in the open state. It is concluded that, like cromakalim, RP 49356 and pinacidil are potent activators of K+-ATP channels in cardiac myocytes.

Adenosine Triphosphate↗

Restrictions on use of creatinine clearance for measurement of renal functional reserve.

The increase of glomerular filtration rate after a 90-gram oral protein load was determined in 9 healthy individuals by simultaneous measurements of both creatinine (Ccr) and inulin (Cin) clearances, performed before and every 30 min during 4 h after the meat meal. This protein load resulted in a short 26% increase of Cin at 90 min, and a sustained 29% increase of Ccr from 90 to 240 min after load. Individual peak values of Ccr occurred later than those of Cin (Ccr: 189 +/- 19 vs. Cin: 127 +/- 19 min; p = 0.023). These discrepancies were related to an increase of serum creatinine, and a subsequent increase of the net tubular excretion of creatinine which accounted for up to 15% of the urinary creatinine. The creatinine content of red meat could lead to overestimation of renal functional reserve when measured by creatinine clearance only.

Adult↗

[Clinicobiological study of drug-induced renal diseases].

The kidney is the main organ involved in drugs elimination and thereby is particularly liable to their toxic effect. The determination of renal function is thus of importance, before and during treatment with a potentially nephrotoxic drug or during trial of new drugs. In this general review, the main methods to measure renal function are briefly analysed. They consist either of simple dosages in blood and urine which allow to roughly evaluate renal functional value and its variations, or more sophisticated investigations which allow a more precise analysis of various nephron functions: glomerular filtration rate and renal plasma flow with measurement of clearances of exogenous markers, determination of basal or maximal tubular activities. The interest of these specific tests is illustrated by the results of a study performed in patients receiving streptozotocin, an antineoplastic nephrotoxic drug. In conclusion, nephrotoxicity of drugs may be in most cases prevented owing to an accurate knowledge of their pharmacokinetics and of risk factors inherent in patients, and to survey of renal function with suitable methods which may lead to modify drug dosage and/or to choose a therapy considering the own evolution of the disease and the possible occurrence of irreversible renal impairment.

Adult↗