Neurologic side-effects of ganciclovir.
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Biomedical subjects
Publications and source records attributed to M Laville.
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Detection of subjects from a multiple endocrine neoplasia type 1 family must rest on clinical, biochemical and radiological data, since study of the genome is unable to detect these subjects. In the new family described here, 6 out of the 14 subjects explored were affected. One had a confirmed pancreatic endocrine tumour and in 3 others a pancreatic endocrine tumour was highly probable, since insulin and glucagon levels, as well as ultrasonic exploration of the pancreas were pathological. Measurements of gastrointestinal hormones gave normal results in all cases. We conclude that to detect this endocrine neoplasia in subjects at risk it seems necessary to measure plasma insulin levels and perform an abdominal ultrasonography.
Massive obesity is defined by a body mass index [weight (kg)/height (m)2] greater than 40. It corresponds to an increase in mortality ratio. Its frequency differs among countries and its incidence is important in USA (13 million subjects), Finland, and South Africa. Obesity is now a serious, emerging problem in developing countries. Frequency of obesity is influenced by age, sex, race and has increased during the last 30 years. Importance of heredity has been highlighted. Recently an increase in superobesity in childhood has been observed, especially in the United States. Finally, besides people with stable obesity throughout their life, there are subjects with weight cycling. These subjects have higher cardio-vascular risks than the others.
To investigate the possible existence of a defect of thermogenesis at the onset of obesity, we studied glucose-induced thermogenesis (GIT) during an oral glucose-tolerance test (OGTT) (1 g/kg body wt) in 12 women who were at the onset of obesity (group A) compared with 12 long-standing obese women (group B) and 8 lean control subjects. During OGTT hyperinsulinemia and glucose intolerance were measured in group B, suggesting an insulin-resistant state, but not in group A. A similar defect in GIT occurred in both obese groups (8.9 +/- 1.5% in control subjects vs 4.2 +/- 1.1% in group A and 4.3 +/- 1.0% in group B, P < 0.05) despite the absence of alteration in nonoxidative glucose metabolism. We conclude that a decrease in GIT already exists at the onset of obesity, which supports the hypothesis of a possible involvement of this defect in the genesis of obesity.
In the human astrocytoma cell line U 373 MG, application of substance P (SP) leads to a transient increase in cytosolic calcium concentration and to a biphasic current response in voltage-clamped cells. Using these two functional assays we have characterized pharmacologically the SP response in U 373 MG cells. SP and [L-Pro9]SP displayed high potencies in both assays with EC50 values of 2.5 x 10(-9) M and 1 x 10(-9) M on calcium responses and 1 x 10(-9) M and 5 x 10(-9) M on ion current responses, respectively. The high potency of SP and [L-Pro9]SP as well as the low potency of [Lys5,MeLeu9,N-Leu10]neurokinin A(4-10) and the inactivity of senktide demonstrate the NK1-type pharmacology of these responses. Furthermore, the NK1 antagonists (+/-)-CP 96,345, its chloro analogue, (+/-)-cis-3-(2-chlorobenzylamino)-2-benzhydrylquinuclidine, and RP 67580 were potent antagonists of both SP responses. For the calcium mobilization induced by SP (10(-7) M), the IC50 values for the three antagonists were 4 x 10(-10) M, 4 x 10(-9) M, and 9 x 10(-9) M, respectively, whereas on the current response evoked by SP (10(-8) M), the IC50 values were 8 x 10(-9) M, 2.4 x 10(-8) M, and 1.2 x 10(-7) M, respectively. Despite differences in the absolute IC50 values obtained with both techniques, the relative potencies of the three antagonists correlate fairly well.(ABSTRACT TRUNCATED AT 250 WORDS)
We describe the first association between Hodgkin's lymphoma and Wegener's granulomatosis, heralded by renal involvement. A 43-year-old man developed rapidly progressive glomerulonephritis requiring chronic hemodialysis 8 months after remission of Hodgkin's lymphoma. At that moment, no extrarenal involvement was found, despite extensive investigation. Antineutrophil cytoplasm antibodies were positive, without specificity for proteinase-3 or myeloperoxydase. Six months after beginning hemodialysis, multiple pulmonary nodules appeared, along with rapid clinical worsening. A surgical biopsy was performed which disclosed a giant cell granuloma. Antimyeloperoxydase antibodies remained negative, whereas proteinase-3 antibodies became positive. Wegener's granulomatosis was diagnosed and treatment with cyclophosphamide and steroids was started. Clinical and radiological improvement occurred promptly. Eleven months after treatment, both Wegener's disease and Hodgkin's lymphoma remained in remission.
Nineteen patients treated by continuous ambulatory peritoneal dialysis (CAPD) were studied according to clinical outcome parameters: insomnia, asthenia, pruritus, arterial hypertension, anorexia, nausea and/or vomiting, anemia, and rate of hospitalization. Using clinical scores, three groups were defined: poor clinical outcome (P), intermediate (I), and good (G). The quantity of treatment by PD was evaluated monthly with urea kinetic tests (weekly Kt/V, weekly urea clearance/1.73 m2 of body surface area (BSA), index of dialysis by Teehan), and with the weekly creatinine clearance/1.73 m2 of BSA. The metabolic index was analyzed: normalized protein catabolic rate (NPCR), serum albumin (Alb) and prealbumin, and reabsorption of glucose. There was good correlation between clinical scores and quantity of dialysis. The Alb was lower in group P. Group G was differentiated from group I and from group P by quantification tests and NPCR, with lower levels as follows: weekly Kt/V = 2.06, urea clearance 70 L/week/1.73 m2, index of dialysis = 0.87, and creatinine clearance = 60 L/week/1.73 m2. We conclude that the qualitative clinical approach is not sufficient to predict deleterious signs, and the quantitative approach is predictive of the good clinical outcome and good nutritional status. We think that levels proposed to now are insufficient, and we suggest the following: weekly urea clearance > 70 L, weekly Kt/V > 2, weekly creatinine clearance > 60 L, and index of dialysis > 0.85.
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OBJECTIVE: To determine whether low protein diets retard the development of end stage renal disease. DESIGN: Meta-analysis of 46 trials since 1975, from which six randomised controlled trials were selected. SETTING: Five trials in Europe and one in Australia between 1982 and 1991. SUBJECTS: 890 patients with mild to severe chronic renal failure who were followed up for at least one year. 450 patients received a low protein diet and 440 a control diet. INTERVENTION: Difference in protein intake between control and treated groups of at least 0.2 g protein/kg/day. MAIN OUTCOME MEASURE: Number of renal deaths (the necessity to start dialysis or death of patient during study). RESULTS: 156 renal deaths were recorded, 61 in the low protein diet group and 95 in the control group, leading to an odds ratio of low protein to control of 0.54 with a 95% confidence interval of 0.37 to 0.79. CONCLUSIONS: This result, obtained on a large population of patients suffering from chronic renal insufficiency, strongly supports the effectiveness of low protein diets in delaying the onset of end stage renal disease.
Recent studies have suggested that the renal effects of high protein intake could be mediated, at least in part, by vasopressin and/or an increase in the urinary concentrating activity. The present study investigated the influence of the level of hydration, and hence of the activity of the concentrating process, on the renal response to an acute oral protein load. Clearance studies were performed before (Control) and during three hours after a protein meal (1.5 g/kg body wt protein as cooked meat) in ten healthy volunteers. This study was performed twice at a two to three week interval under either constant low (LowH) or high (HighH) hydration. In spite of the marked difference in initial diuresis (3.1 +/- 0.3 in LowH vs. 13.9 +/- 0.7 ml/min in HighH) and urine osmolality (501 +/- 42 in LowH vs. 99 +/- 3 mOsm/kg H2O in HighH), a similar relative decrease in urine flow rate was observed following the meal in both conditions. TcH2O increased progressively by 70% in LowH whereas CH2O decreased by 40% in HighH. Plasma vasopressin showed a progressive increase with time in LowH (from 1.10 +/- 0.26 in control, to 1.98 +/- 0.35 pg/ml at the third hour after the PM, P < 0.05) but not in HighH (0.53 +/- 0.09 to 0.70 +/- 0.17 pg/ml). Glomerular filtration rate (inulin clearance) increased significantly on the second post-prandial hour under LowH but not under HighH. Excretions rates of Na, Cl, K, and urea increased after the meal, however, not to the same extent nor with the same time course in the two conditions. Significant positive correlations were observed between GFR and TcH2O, urine osmolality, or the ratio of urine-to-plasma urea concentrations in LowH. These results suggest that the protein-induced hyperfiltration is partially blunted by a high water intake, and hence is dependent, directly or indirectly, on the urine concentrating activity.
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Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors.
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We performed a nutritional trial to assess the variations of circulating insulin-like growth factor-I (IGF-I) in chronic renal failure (CRF). Eight patients suffering from mild renal failure (SCr = 374 +/- 52 mumol/l) were prescribed a standard diet for 1 month followed by 1 month of protein restriction. Mean protein intake was 0.77 and 0.46 g/kg BW/day, mean caloric intake 25 and 24.7 kcal/kg BW/day for the first and the second month, respectively. After each period of diet, nitrogen balances were negative (-1.2 +/- 1.6 and -1.6 +/- 0.9 g/N/day). Despite these low-caloric conditions, mean serum IGF-I level was at the upper level of normal (358 +/- 136 ng/ml) after 1 month of standard protein intake, and statistically reduced (289 +/- 122 ng/ml, p < 0.002) by the low-protein diet. No correlation was observed between serum IGF-I levels and protein, caloric intake, and nitrogen balances for the two periods. Estimation of the IGF-I binding by the ratio of extracted to nonextracted IGF-I value suggested abnormal binding in CRF. This binding was modified by reduced protein intake. In conclusion, larger studies are needed in CRF to assess the significance of IGF-I variations and the IGF-I binding proteins which modulate the bioactivity of this growth factor.
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The finding of microscopic haematuria in the course of systematic screening accounts for 10 percent of consultations in nephrology clinics. We carried out an investigation in a population of 8,194 workers of the metallurgical and chemical industries, 89.6 percent of whom were male and 69.8 percent were under 49 years of age; 51.2 percent were smokers or ex-smokers, 9.9 percent had arterial hypertension and 2.1 percent had diabetes mellitus. Microscopic haematuria was detected by the dipstick method in 3.53 percent of the subjects tested. Phase contrast microscopy, performed in 222 subjects, showed that the origin of the haematuria was glomerular in 90.5 percent, extraglomerular in 2.5 percent and undetermined in 0.9 percent of the cases. Urinary sediment was normal in 6.3 percent. The prevalence of microscopic haematuria was significantly higher in women, in subjects under 49 years of age, in hypertensive subjects, in smokers or ex-smokers, in subjects who has received non-steroidal anti-inflammatory drugs during the past 6 months and in chemical industry workers.
To determine the effect of insulin and glucagon on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB), we measured simultaneously in normal subjects NEFA and KB kinetics at different NEFA levels in the presence of basal (control test) or increasing insulin concentrations with glucagopenia (somatostatin + insulin infusion, insulin test) and without glucagopenia (somatostatin + insulin + glucagon infusion, glucagon test). NEFA levels were controlled during these tests by an intravenous (IV) infusion of a triglyceride emulsion. During the control test, a moderate increase of NEFA (464 +/- 30 to 715 +/- 56 mumol/L) increased the percentage of NEFA converted into KB (13.3% +/- 1.4% to 26.4% +/- 2.1%, P less than .05), and there was a linear relationship between this percentage and NEFA levels (r = .788, P less than .01). During the insulin and glucagon tests, the progressive increase in NEFA induced by the triglyceride emulsion infusion was associated, despite the increase of insulinemia, with an increase in KB production rate (P less than .05) and in the proportion of NEFA used for ketogenesis in the presence (8.1% +/- 1.2% to 14.2% +/- 6.3%, P less than .05) and absence (15.7% +/- 2.8% to 25.2% +/- 3.99%, P less than 0.05) of glucagopenia. In both tests, this percentage was always linearly related with NEFA levels (P less than .05) and the slopes of these relationships were comparable to that observed in the control test. However, the fraction of NEFA used for ketogenesis was always higher (P less than .05) during glucagon substitution than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)