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Biomedical subjects

M Laville

Publications and source records attributed to M Laville.

At least 91 records · Page 5Linked to original sources
PubMed1999

Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes.

Peroxisome proliferator-activated receptor (PPAR)-gamma is one of the key actors of adipocyte differentiation. This study demonstrates 1) that PPAR-gamma mRNA expression is not altered in subcutaneous adipose tissue (n = 44) or in skeletal muscle (n = 19) of subjects spanning a wide range of BMIs (20-53 kg/m2) and 2) that insulin acutely increases PPAR-gamma mRNA expression in human adipocytes both in vivo and in vitro. The effect of insulin was investigated in abdominal subcutaneous biopsies obtained before and at the end of a 3-h euglycemic-hyperinsulinemic clamp. Insulin significantly increased PPAR-gamma mRNA levels in lean subjects (88 +/- 17%, n = 6), in type 2 diabetic patients (100 +/- 19%, n = 6), and in nondiabetic obese patients (91 +/- 20%, n = 6). Both PPAR-gamma1 and PPAR-gamma2 mRNA variants were increased (P < 0.05) after insulin infusion. In isolated human adipocytes, insulin induced the two PPAR-gamma mRNAs in a dose-dependent manner, with half-maximal stimulation at a concentration of approximately 1-5 nmol/l. However, PPAR-gamma2 mRNA was rapidly (2 h) and transiently increased, whereas a slow and more progressive induction of PPAR-gamma1 was observed during the 6 h of incubation. In explants of human adipose tissue, PPAR-gamma protein levels were significantly increased (42 +/- 3%, P < 0.05) after 12 h of incubation with insulin. These data demonstrate that PPAR-gamma belongs to the list of the insulin-regulated genes and that obesity and type 2 diabetes are not associated with alteration in the expression of this nuclear receptor in adipose tissue.

Adipocytes↗
PubMed1999

Noninvasive exploration of cardiac autonomic neuropathy. Four reliable methods for diabetes?

OBJECTIVE: The purpose of this work was to assess relevant information that could be provided by various mathematical analyses of spontaneous blood pressure (BP) and heart rate (HR) variabilities in diabetic cardiovascular neuropathy. RESEARCH DESIGN AND METHODS: There were 10 healthy volunteers and 11 diabetic subjects included in the study. Diabetic patients were selected for nonsymptomatic orthostatic hypotension in an assessment of their cardiovascular autonomic impairment. Cardiac autonomic function was scored according to Ewing's methodology adapted to the use of a Finapres device. The spontaneous beat-to-beat BP and HR variabilities were then analyzed on a 1-h recording in supine subjects. The global variabilities were assessed by standard deviation, fractal dimension, and spectral power. The cardiac baroreflex function was estimated by cross-spectral sequences and Z analyses. RESULTS: In diabetic patients, Ewing's scores ranged from 1 to 4.5, confirming cardiovascular autonomic dysfunction. In these diabetic patients, global indices of variabilities were consistently lower than in healthy subjects. Furthermore, some of them (standard deviation and fractal dimension of HR, spectral power of systolic blood pressure and HR) were significantly correlated with the Ewing's scores. The Z methods and the spectral analysis found that the cardiac baroreflex was less effective in diabetic subjects. However, the baroreflex sensitivity could not be reliably assessed in all the patients. The sequence method pointed out a decreased number of baroreflex sequences in diabetic subjects that was correlated to the Ewing's score. CONCLUSIONS: Indices of HR spontaneous beat-to-beat variability are consistently related to the degree of cardiac autonomic dysfunction, according to Ewing's methodology. The Z method and spectral analysis confirmed that the cardiac baroreflex was impaired in diabetic patients. These methods might be clinically relevant for use in detecting incipient neuropathy in diabetic patients.

Adult↗
PubMed1999

[Clinical importance of fetal pulse oximetry. I. Methodological evaluation. Multicenter study. French Study Group on Oximetry of Fetal Pulse].

OBJECTIVE: To evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relation with the neonatal outcome in a population with an abnormal fetal heart rate (FHR). STUDY DESIGN: A prospective multicenter observational study, from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded using a Nellcor N-400 fetal pulse oximeter in case of abnormal FHR during labor. Simultaneous readings of fetal oxygen saturation and of fetal blood analysis (FBA) were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values and relation with neonatal outcome were assessed. RESULTS: 74 patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than FBA attempt (easy in 87.5% vs 78.9% for FBA, p = 0.03). The mean reliable signal time (+/- SD) was 64.7 +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2 +/- 8.0% (10th-90th centile range: 30-53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29; p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between a low fetal oxygen saturation (< 30%) and a poor neonatal condition. CONCLUSION: The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.

Adult↗
PubMed1999

[Clinical importance of fetal pulse oximetry. II. Comparative predictive values of oximetry and scalp pH. Multicenter study].

OBJECTIVE: To compare the predictive value of intrapartum fetal pulse oximetry to that of fetal blood analysis for an abnormal neonatal outcome in case of abnormal fetal heart rate (FHR). STUDY DESIGN: A prospective multicenter observational study, from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded using a Nellcor N-400 fetal pulse oximeter in case of abnormal FHR during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth, i.e. either at full dilatation, or before cesarean section when indicated, were compared with the neonatal status. The criteria for an abnormal neonatal outcome were 1) an umbilical arterial blood pH < or = 7.15 and 2) a combined variable including: 5 min. Apgar score < or = 7, umbilical arterial pH < or = 7.15, secondary respiratory distress, transfer in a neonatal care unit, or neonatal death. RESULTS: At a 7.20 threshold for fetal scalp pH, and 30% for fetal oxygen saturation (i.e. the tenth centile in the study population), the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pH < or = 7.15, and for an abnormal neonatal outcome (positive predictive value 56% vs 55%, negative predictive value 81% vs 82%, sensitivity 29% vs 35%, and specificity 93% vs 91% respectively). The receiver operating curve showed similar performance of either technique for cut-off values < or = 7.20 for fetal blood pH and < or = 30% for fetal oxygen saturation, whereas fetal pulse oximetry became superior at higher thresholds. CONCLUSION: The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis. Randomized controlled management trials can now be performed to assess potential clinical benefits of this new tool.

Female↗
PubMed1999

[Phenotypes of essential arterial hypertension in Caribbean women].

UNLABELLED: The characterisation of phenotypes of patients with essential hypertension (EH) is an important pre-requisite for genetic research. The present study compares clinical and renal function parameters in 2 groups of patients from different origins. METHOD: Out of a cohort of essential hypertensives disclosed on routine work medical examinations, 21 caucasian (CC) women were paired with 21 Caribbean (CB) women. In the 2 groups we recorded family history of hypertension (FHH), duration of hypertension, BMI, salt intake based on 24 h urinary sodium excretion, microalbuminuria, and blood pressure (BP). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured with inulin and para-amino-hippuric acid clearances. Plasma active renin (AR) and aldosterone (Aldo) levels were measured by immuno-assays. White coat (WC) effect was assessed on the difference between BP values measured on medical visits and by the nurses on clearance measurements. Anova and t-test were used for analysis, statistical significance was assumed for p < 0.05. RESULTS: Casual BP values were 150/94 mmHg in CB and 153/95 mmHg in CC. There were no significant differences on BMI (CB 30.6 kg/m2 vs CC 27.1 kg/m2). AR (CB 6.6 pg/mL vs CC 8.7 pg/mL) and Aldo (CB 195.1 pmol/L vs CC 202.8 pmol/L) provided an equivalent dietary salt intake (CB 11.2 g/d vs CC 10.7 g/d). Mother FHH was found predominantly in CB women (60% vs 30% in CC, p < 0.05), whereas paternal FHH was more frequent in CC women (21% vs 8% in CB, p < 0.05). At the same age, duration of hypertension was longer by 1 year in CB. White coat effect was more marked in CC (BP > 30 mmHg: 40% in CC vs 5% in CB, p < 0.05). GFR values were normal and similar in CB and CC women. But a significantly lower RPF was measured in CB (489 vs 542 mL/min/1.73 m2 in CC, p < 0.05). Higher filtration fraction and microalbuminuria were also observed in CB women. CONCLUSION: Essential hypertension occurs at younger ages in Caribbean women. The decrease in RPF could be genetically determined and is likely to participate in early onset of hypertension, as previously described in young normotensive subjects. In paired women, we did not found significant differences in active renin and aldosterone levels. The ongoing longitudinal study should contribute to assess the consequences of these findings on renal prognosis and the effects of antihypertensive therapy.

Caribbean Region↗
PubMed1999

Blood compartmental metabolism of docosahexaenoic acid (DHA) in humans after ingestion of a single dose of [(13)C]DHA in phosphatidylcholine.

The amount and distribution of [(13)C]docosahexaenoic acid (DHA) in plasma, platelet, and erythrocyte lipid classes were followed as a function of time (1 to 72 h) in young adults after ingestion of a single dose of [(13)C]DHA esterified in a phosphatidylcholine (PC), in using gas chromatography combustion;-isotope ratio mass spectrometry. [(13)C]DHA first appeared in plasma non-esterified fatty acids (NEFA) and triglycerides (TG), with a maximal appearance at 6 h and a further decline, then being delayed 3-fold compared to [(13)C]DHA ingested in triglycerides. Lysophosphatidylcholine (LPC) was also enriched in [(13)C]DHA, due mainly to earlier hepatic secretion, and plateaued at 6 h, whereas phosphatidylethanolamine (PE) and phosphatidylcholine (PC) containing [(13)C]DHA plateaued at 9 h. The labeling of erythrocyte and platelet phospholipids exhibited different kinetics, probably involving different metabolic pathways for [(13)C]DHA incorporation in cell membranes. Computation of the relative contribution of LPC and NEFA for delivery of [(13)C]DHA to blood cells showed that the supply to platelets occurred through NEFA. In contrast, [(13)C]DHA was carried by both LPC and NEFA to erythrocytes, which differs from what was previously been observed after intake of triglycerides labeled with [(13)C]DHA where LPC was the only source of [(13)C]DHA for erythrocytes. We conclude that the lipid form of ingested DHA affects markedly its kinetics and partly its metabolic fate.

Adult↗
PubMed1999

Interstitial alpha-smooth muscle actin: a prognostic marker in membranous nephropathy.

AIM: Membranous nephropathy in adults causes 20% of nephrotic syndromes. Spontaneous outcome of this glomerulopathy is difficult to evaluate from clinical and histological data. Some patients can achieve complete remission, while others develop progressive renal failure. In this study we assessed alpha-smooth muscle actin (alpha-SMA) expression in renal interstitial myofibroblasts as a marker to predict the outcome of membranous nephropathy. PATIENTS AND METHODS: Renal function tests in tandem with alpha-SMA immunolabelling were performed on 25 patients with a mean follow-up of 7.2+/-5.6 years. The intensity of interstitial alpha-SMA (ialpha-SMA) immunostaining was compared to changes in glomerular filtration rate (GFR) evaluated by inulin clearance, between the time of diagnosis (GFR1) and the end of follow-up (GFR2). RESULTS: A significant correlation (r = 0.62, p<0.001) was found, between the intensity of interstitial myofibroblasts, immunolabeling and GFR at the end of follow-up. Moreover, the annual GFR variation and the annual percentage of GFR variation were correlated to interstitial myofibroblast labeling (respectively r = 0.62, p<0.001; r = 0.67, p<0.001). In addition, the importance of proteinuria, initial GFR impairment and fibrosis were confirmed as prognostic criteria. CONCLUSION: This study strongly shows that ialpha-SMA expression is a useful and early prognostic marker in the evolution of membranous nephropathy.

Actins↗
PubMed1998

mRNA expression of the long and short forms of uncoupling protein-3 in obese and lean humans.

Uncoupling protein-3 (UCP3) is a mitochondrial protein expressed in skeletal muscle, an important site of thermogenesis in humans. By uncoupling respiration from ATP synthesis, UCP3 might be involved in the control of energy expenditure. Two transcripts encoding long (UCP3L) and short (UCP3S) form are generated from the human UCP3 gene. UCP3S is predicted to encode a protein which lacks the C-terminus of UCP3L, a region which contains motifs critical for uncoupling activity. We have investigated the regulation of UCP3L and UCP3S mRNAs in lean and obese humans. A specific reverse transcription-competitive polymerase chain reaction assay was developed to separately quantify the two mRNAs. Each transcript represents half of total UCP3 mRNA in 16 vastus lateralis muscle samples. The amounts of UCP3L and UCP3S mRNAs did not differ between obese and lean subjects. The effect of fasting was studied in six lean and seven obese subjects maintained on a hypocaloric diet (1045 kJ/d) for 5 days. Calorie restriction results in an approximately threefold increase of UCP3L and UCP3S mRNA levels. The induction was similar in lean and obese subjects. The data suggest that there is no major alteration of UCP3 gene expression and regulation at the level of transcription and alternative splicing in skeletal muscle of obese subjects.

Adult↗
PubMed1998

Paget's disease versus Toker cell hyperplasia in a supernumerary nipple.

We report the second case of mammary Paget's disease arising in a supernumerary nipple of a 29-year-old woman. The epithelium of the nipple was infiltrated by large cells with abundant and pale-staining cytoplasm. The nuclei had a vesicular chromatin pattern and identifiable nucleoli. The cells were strongly immunoreactive with KL1, CEA and EMA, but did not show reactivity with PS100, HMB45, or erb-B2. The pathogenesis of Paget cells is unclear. In our case, the lesion showed nearly all the clinical, histological and histochemical characteristics of Paget's disease, though without involvement of mammary gland epithelium and underlying carcinoma. The possibility of an intraepidermal origin, either by transformation from epidermal keratinocytes or by derivation from intraepidermal precursor cells, has to be considered. The differential diagnosis against Toker cell hyperplasia is also discussed.

Adult↗
PubMed1998

Acute leptin regulation in end-stage renal failure: the role of growth hormone and IGF-1.

BACKGROUND: Leptin, a recently discovered peptide involved in nutrient intake and energy expenditure, has been shown to be abnormally regulated in certain conditions such as obesity. In chronic renal failure, leptin appears to be increased. However, little is known about leptin regulation during chronic renal failure (CRF). METHODS: We measured serum leptin in eight well nourished, chronic hemodialysis patients (seven males, one female) receiving anabolic factors for three days as either recombinant insulin-like growth factor-1 (rhIGF-1) or a combination of recombinant growth hormone (rhGH) plus recombinant IGF-1, in a random cross-over trial. RESULTS: Serum leptin values were in the range of normal volunteers matched for body mass index. As reported in other conditions, serum leptin was strongly correlated with patients dry body wt (P = 0.01) and body fat (P = 0.0001). Both treatments affected serum leptin in a rapid and opposite manner. RhIGF-1 decreased serum leptin from 11.2+/-20.8 (SD) to 4.3+/-3.8 microg/liter (P = 0.011), whereas the combination of rhGH + rhIGF-1 increased serum leptin from 7.4+/-9.4 to 21.0+/-32.9 microg/liter (P = 0.011). Regression analyses indicated a linear regression between serum leptin and insulin variations after treatment. CONCLUSIONS: This study shows for the first time that both rhIGF-1 and rhGH acutely regulate serum leptin in dialysis patients. Whether leptin changes are explained by the concomitant insulin variation should be further studied under renal failure conditions.

Adult↗
PubMed1998

Influence of human obesity on the metabolic fate of dietary long- and medium-chain triacylglycerols.

The metabolic fate of an oral long-chain-triacylglycerol (LCT) load and of a mixed oral LCT and medium-chain-triacylglycerol (MCT) load was followed for 6 h in eight control and eight obese subjects with normal postabsorptive triacylglycerol concentrations. Labeled triacylglycerol and indirect calorimetry were used. Results showed that LCTs were less oxidized in obese than in control subjects (3.2+/-0.5 compared with 6.0+/-0.4 g, P < 0.01). Moreover, the amount of LCT oxidized was negatively correlated with fat mass (r = -0.77, P < 0.01). Appearance in plasma of dietary triacyglycerol-derived long-chain fatty acids was blunted in obese subjects and it was negatively related to fat mass (r = -0.84, P < 0.01) and positively to LCT oxidation (r = 0.70, P < 0.01). On the contrary, MCT oxidation was not altered in obese subjects compared with control subjects. Furthermore, the proportion of MCTs oxidized was higher in both groups compared with LCTs (x+/-SEM: 57.5+/-2.6% compared with 15.2+/-1.6%, P < 0.01, n = 16). Our conclusion is that obesity is associated with a defect in the oxidation of dietary LCTs probably related to an excessive uptake by the adipose tissue of meal-derived long-chain fatty acids. MCTs, the oxidation of which is not altered in obesity, could therefore be of interest in the dietary treatment of obesity.

3-Hydroxybutyric Acid↗
PubMed1998

Effects of moxonidine on stress-induced peak blood pressure and renal function: a randomized, double-blind, placebo-controlled crossover study.

Moxonidine is an imidazoline I1-receptor agonist that centrally acts by reducing the sympathetic tone. Furthermore, proximal tubular I1-receptors have been isolated in human kidneys, but their natriuretic effects have never been demonstrated. Because stress tests elicited a sympathetically mediated increase in blood pressure and in sodium reabsorption, the aim of this study was to assess the effects of moxonidine (0.4 mg/day; 1 month) on stress-induced cardiovascular response and renal sodium handling in hypertensives, in a double-blind, crossover, placebo-controlled study. The stress test used is an efficient and reproducible computerized version of Stroop's stress test. During the experimental sessions, both rest and stress renal functional parameters were determined: glomerular filtration rate (inulin clearance), renal plasma flow (para-aminohippurate clearance), filtration fraction, sodium excretion, and segmental sodium tubular reabsorption (lithium clearance). During the placebo phase, stress induced a significant increase in systolic blood pressure (deltaSBP; 15.8+/-10.7 mm Hg) and diastolic blood pressure (deltaDBP; 8.2+/-6.1 mm Hg). During stress, glomerular filtration rate tended to decrease, whereas renal plasma flow significantly decreased, resulting in a significant increase in filtration fraction. Despite the increase in BP, stress induced a decrease in sodium excretion that was mainly due to a nonsignificant increase in sodium reabsorption in the proximal parts of the tubules. Moxonidine significantly reduced rest and stress BP, but the stress cardiovascular reactivity was not altered. At rest, renal function was well preserved by the treatment. Stress-induced modifications in renal function and sodium handling were not altered by the treatment. In conclusion, moxonidine reduced rest and stress-induced peak BP and preserved basal renal function. The study failed to demonstrate any effect of moxonidine either on basal renal sodium handling or on stress-induced increase in sodium reabsorption.

Adult↗
PubMed1998

Effects of recombinant growth factors on energy expenditure in maintenance hemodialysis patients.

We compared the metabolic effects of recombinant human (rh) insulin-like growth factor (IGF)-1 or a combination of rhIGF-1 + rh growth hormone (GH) on resting energy expenditure (REE) in 8 maintenance hemodialysis (MHD) patients. Seven males and 1 female (aged 41.6 +/- (SD) 12.4) with no evidence of malnutrition (BMI 21.6 +/- 2.2 kg/m2, serum albumin 45 +/- 2 g/l, serum IGF-1 359 +/- 165 microg/l) received either rhIGF-1 (80 microg/kg/day) or rhIGF-1 (80 microg/kg/day) + rhGH (50 microg/kg/day) for 3 days in a random crossover design. REE and the respiratory quotient (RQ) were measured at rest before and after the 3-day treatment. The results confirmed that MHD patients have a REE not different from normal individuals. REE was strongly correlated with lean body mass but not with fat mass. rhIGF-1 treatment did not modify REE despite doubling serum IGF-1 values, whereas a combined rhIGF1 + rhGH treatment significantly increased REE by 11% (p < 0.001). There was no change in RQ under both treatments, in response to a proportionate increase in VCO2 and VO2. These results show that energy expenditure is mainly dependent upon lean body mass in well-nourished MHD patients. The metabolic effects of rhIGF-1 and rhGH on energy expenditure may differ in response to their opposite effects on lipid oxidation and insulin regulation.

Adult↗
PubMed1998

Depot-specific differences in adipose tissue gene expression in lean and obese subjects.

Intra-abdominal and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral, but not subcutaneous, fat with obesity-related cardiovascular and metabolic problems. Because the molecular mechanisms contributing to these differences are not yet defined, we compared by reverse transcription-polymerase chain reaction the expression of 15 mRNAs that encode proteins of known importance in adipocyte function in paired omental and subcutaneous abdominal biopsies. No difference in mRNA expression between omental and subcutaneous adipose tissue was observed for hormone sensitive lipase, lipoprotein lipase, 6-phosphofructo-1-kinase, insulin receptor substrate 1, p85alpha regulatory subunit of phosphatidylinositol-3-kinase, and Rad. Total amount of insulin receptor expression was significantly higher in omental adipose tissue. Most of this increase was accounted for by expression of the differentially spliced insulin receptor lacking exon 11, which is considered to transmit the insulin signal less efficiently than the insulin receptor with exon 11. Perhaps consistent with a less efficient insulin signaling, a twofold reduction in GLUT4, glycogen synthase, and leptin mRNA expression was observed in omental adipose tissue. Finally peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA levels were significantly lower in visceral adipose tissue in subjects with a BMI <30 kg/m2, but not in obese subjects, indicating that relative PPAR-gamma expression is increased in omental fat in obesity. This suggests that altered expression of PPAR-gamma might play a role in adipose tissue distribution and expansion.

Adipose Tissue↗
PubMed1998

Acetate-free biofiltration for acute renal failure.

The characteristics of acetate-free biofiltration (AFB) are now well documented in patients with chronic renal failure: hemodynamic tolerance, correction of acid-base imbalance, buffer-free dialysate (without acetate) and absence of backfiltration. This hemodialysis technique can be beneficial to patients with acute renal failure (ARF). In our intensive care unit, we prospectively studied 29 patients with isolated ARF or ARF associated with failure of other organs. All eligible patients were randomly assigned to undergo dialysis with bicarbonate hemodialysis (BH) or with (AFB). All used the same high flux biocompatible dialysis membranes. Effectiveness and hemodynamic tolerance of hemodialysis sessions and evolution of patients were analyzed. Correction of metabolic disorders, although better in the AFB group was not statistically different from that in the BH group. Re-equilibration of acid-base balance was also similar, with or without mechanical ventilation. Heparin consumption was significantly higher in the AFB group, with no effect on haemorrhagic complications. Analysis of hypo- and hypertensive episodes, defined as arterial pressure (AP) variations 20% greater than initial pressure, showed no difference in terms of number or degree of AP variation. However, weight loss and the rate of ultrafiltration led to a higher hypotensive risk in the BH group (p < 0.05). Finally, the clinical course and prognosis was similar in both groups. In summary, AFB may be considered as effective a hemodialysis technique as BH in patients with ARF. Weight loss was better tolerated in the AFB group and can be a favorable factor considering the deleterious effect of overhydration in patients admitted to an intensive care unit. This study invites a comparison of longer dialysis session of AFB therapy and continuous hemodiafiltration.

Acid-Base Equilibrium↗