APOE ε4 allele is associated with an increased risk of bulbar-onset amyotrophic lateral sclerosis in men.

OBJECTIVE: Several association studies have identified possible susceptibility factors for sporadic amyotrophic lateral sclerosis (SALS). Studies on the APOE gene provided conflicting results, especially about the effect on bulbar onset. We assessed the possible role of APOE gene in a large cohort of patients with ALS and matched controls. METHODS: The APOE alleles were determined in 1482 patients with SALS and 955 controls and analysed by univariate and multivariate statistics, taking into account gender, site-of-onset and age-at-onset. RESULTS: Patients with bulbar onset were more likely to be women [odds ratio (OR)=2.17; 95% CI: 1.74-2.72] and to be older (OR=3.47; 95% CI: 2.58-4.67). The ε4-carriers were more frequent in the bulbar-onset group than in the limb-onset group (OR=1.39 bulbar onset versus limb onset; 95% CI: 1.08-1.80) but this association was observed amongst men (OR=1.78; 95% CI: 1.25-2.53) and not women (OR=1.09; 95% CI: 0.75-1.59). CONCLUSION: Our study provides evidence for a contribution of the ε4 allele in the occurrence of bulbar-onset ALS amongst men. We propose that men are normally protected by androgens against bulbar onset and that the ε4 allele inhibits this protection, perhaps by interfering with the androgen pathway.

Apolipoprotein E genotype and plasma lipid levels in Caucasian diabetic patients.

OBJECTIVE: Apo E polymorphism has been shown to affect lipid profiles in non-diabetic and diabetic populations. We evaluated the relationship between Apo E phenotype and fasting lipid plasma levels in type 2 diabetes patients. METHODS: Two hundred and ten French type 2 diabetic patients (115 men and 95 women) without any lipid lowering drugs were studied. Fasting lipids were measured by usual methods and Apo E genotype was established for each patient: PCR was followed by digestion of the amplification product with restriction enzymes and separation of the fragments by polyacrylamide gel. RESULTS: Genotypes epsilon3/epsilon3, epsilon2/epsilon3 and epsilon3/epsilon4, epsilon2/epsilon2 and epsilon2/epsilon4 were found in 68.1%, 14.8%, 15.7%, 1.0% and 0.5%, respectively. No patient had the epsilon4/epsilon4 genotype. Lipid plasma levels were compared between E3 group (epsilon3/epsilon3) as a reference and E2 (epsilon2/epsilon2 or epsilon2/epsilon3) or E4 (epsilon3/epsilon4 or epsilon2/epsilon4). Total cholesterol, LDL cholesterol and Apo B levels were lower in the E2 group. Total cholesterol, LDL cholesterol and Apo B levels were higher in the E4 group. HDL cholesterol levels were increased in the E4 group, as only previously observed in Japanese populations. CONCLUSION: These results agree with those already reported in diabetic patients of several western European countries. E4 allele carriers have a greater cardio-vascular risk and this could be partially explained by the metabolic variation in lipid metabolism induced by E4 with higher LDL cholesterol and Apo B levels. These results observed in French diabetic subjects without any lipid-lowering drugs may be used as a reference for other studies performed in France.

Changes in plasma triacylglycerol concentrations after sequential lunch and dinner in healthy subjects.

OBJECTIVES: The present study examines the kinetic of plasma triacylglycerol (TAG) after sequential ingestion of lunch and dinner as well as the contribution of dietary fat ingested at lunch to subsequent post-dinner TAG composition. METHOD: Six healthy subjects were included. After standardized breakfast (7: 30AM), 2 mixed meals with fat loads composed of 44 g olive oil (rich in oleic acid) at lunch (12PM) and 44 g sunflower oil (rich in linoleic acid) at dinner (7PM) were ingested. [1-13C] palmitate was added in lunch only. Plasma TAG and chylomicron-TAG (CMTAG) levels were measured sequentially after meals. [1-13C] palmitate enrichment and concentrations of oleic acid and linoleic acid were measured in all lipid fractions. RESULT: Post-dinner plasma TAG peak was delayed as compared to lunch (3 hours vs 1 hour, p=0.002) whereas the magnitude of the postprandial peaks was not significantly different between lunch and dinner (2.4+/-0.3 vs 2.0+/-0.4 mmol/L, p=0.85). [1-13C] palmitate enrichment was maximal 5 hours after lunch in all lipid fractions and decreased slowly thereafter. After dinner ingestion, the rate of decline of [1-13C] palmitate enrichment plateaued during the first 60 minutes. Oleic acid increased slightly and immediately after dinner and remained the predominant fatty acid in all lipid fractions during the first hour after dinner. A delayed peak of plasma and CM-TAG was observed after dinner as compared to lunch without difference in the magnitude of peaks. CONCLUSION: The contribution of dietary fat ingested at lunch to post-dinner lipemia is confirmed despite the relatively long lasting interval between the 2 meals (7 h) and the absence of any early peak of plasma TAG after dinner.

[Is procalcitonin able to help in pediatric appendicitis diagnosis?]. / La procalcitonine peut-elle aider au diagnostic des appendicites de l'enfant?

BACKGROUND: Appendicitis clinical diagnosis in children is difficult and the acute inflammatory markers hyperleucocytis and CRP do not contribute to it. OBJECTIVE: To study the predictive value of procalcitonin (PCT) and to assess variations of its serum level according to inflammatory lesions in paediatric appendicitis. PATIENTS AND METHOD: Among 101 children aged two and 15, hospitalized for painful abdominal syndromes, 70 underwent operation for acute appendicitis and appendiceal peritonitis, 31 had no operation. PCT was evaluated in all children, normal serum concentration was <0,5 microg/L. Every appendicectomy part has been examined through histological analysis to confirm the diagnosis and the histological lesions have been classified into three categories according to their severity. RESULTS: Out of 70 appendix analysed at histology, 68 (97%) were healthy and 2 (3%)were unhealthy. Among the 68 cases of healthy appendix, 19 had a PCT higher than 0,5 microg/L and among 33 cases of unhealthy appendix 4 had a PCT higher than 0,5 microg/L. The PCT mean of healthy children was not significantly different from unhealthy appendix population, appendicitis prevalence was 0,67, PCT sensitivity 28%: IC 95% [18-40], specificity 88%: IC 95% [72-97], positive predictive value 83%: IC 95% [61-95], and negative predictive value 37%: IC 95% [26-49]. PCT mean increases with the severity of inflammatory lesions of the appendix (P=0,0051). CONCLUSION: PCT has not a good predictive value in acute paediatric appendicitis but remains a good indicator of severity in paediatric appendicitis.

Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes.

AIMS/HYPOTHESIS: Cardiovascular complications and particularly coronary heart disease are the main causes of morbidity and mortality in Type II (non-insulin-dependent) diabetes mellitus. Some studies have shown that hypertriglyceridaemia in diabetes is an independent cardiovascular risk factor. In the ECTIM study high apolipoprotein C3 and lipoprotein B:C3 concentrations (lipoparticles playing a role in triglyceride metabolism) were associated with myocardial infarction in non-diabetic subjects. METHODS: We studied the relations between macroangiopathy and different cardiovascular risk factors and lipid variables in 188 Type II diabetic subjects. RESULTS: Multivariate analysis showed that triglycerides, apo C3 and Lp B:C3, sex, duration of diabetes, microalbuminuria and age were independently associated with macroangiopathy. The study group was divided into quartiles according to apo C3 and Lp B:C3 concentrations: the prevalence of macroangiopathy and coronary heart disease were increased in upper quartiles. CONCLUSION/INTERPRETATION: Triglycerides apo C3 and Lp B:C3 were independent cardiovascular risk markers in our group of Type II diabetic patients.

Sex differences in the control of sex-hormone-binding globulin in the elderly: role of insulin-like growth factor-I and insulin.

OBJECTIVE: Serum levels of sex-hormone-binding globulin (SHBG) have been reported in the literature to increase with age in both sexes. We have investigated the variations in levels of androgens, insulin and IGF-I with age and have evaluated their putative roles to obtain a better understanding of the increase in SHBG. DESIGN: Cross-sectional pilot study of blood samples in healthy elderly subjects aged 50 to 90 years. PATIENTS AND METHODS: Forty-four postmenopausal women and 40 men were classified into three age groups. Subjects who were obese, undernourished or smokers and postmenopausal women receiving hormone replacement therapy were excluded from the study. Body mass index and waist/hip ratio were evaluated in each subject. Fasting levels of blood glucose, insulin, triglycerides, cholesterol, SHBG, testosterone, dehydroepiandrosterone sulfate (DHEAS) and IGF-I were measured. Free testosterone and glucose/insulin ratio were calculated. RESULTS: The results are based on variance analysis of the mean of each parameter in the three age groups. Multiple regression analysis was performed to define the role of age, insulin and IGF-I in the increase in SHBG. The increase in SHBG with age in older men was significant but that in postmenopausal women was not. Decreasing DHEAS with age was confirmed. No significant variations in glucose and insulin were observed with age in our selected population. A positive correlation was observed between insulin and triglycerides in elderly men and women. IGF-I decreased significantly with age in both sexes. Insulin was the main factor explaining SHBG increase with age in women. In men, both age and IGF-I contributed to the SHBG increase. CONCLUSIONS: The factors regulating the increase in SHBG with age appear to be different in the two sexes. Insulin plays a major role in women, whereas a decrease in IGF-I is the predominant regulating factor in men. These results should be thought of as a working hypothesis rather than a reflection of physiology.

Metabolic and hormonal changes induced by hypodermoclysis of glucose-saline solution in elderly patients.

BACKGROUND: Hypodermoclysis, i.e., infusion of solutions into the subcutaneous tissues, is an alternative method for hydration. The aim of our study was to describe the metabolic changes induced by hypodermoclysis of a glucose-saline solution in elderly patients. METHODS: Twelve experiments were conducted in a random cross-over study, intravenous infusion (IV) vs subcutaneous infusion (SC), in 6 hospitalized patients (81.5 +/- 9.8 years). The solution (1000 mL of 5% glucose solution containing 4 g NaCl) was infused over 6 hours in fasted patients who remained in bed. Blood was sampled at -10, 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes for measurement of plasma concentrations of glucose, insulin, free fatty acids, and beta-hydroxybutyrate. Plasma concentration of cortisol was analyzed only at T-10, T0, T180, and T360. RESULTS: The increases in glucose and insulin and the decrease in plasma concentrations of free fatty acids were lower with SC infusion than with IV infusion. The decrease in beta-hydroxybutyrate plasma concentration was lower at T300 with SC infusion than with IV infusion. The decrease in cortisol did not differ with the route. Plasma concentrations of all compounds were similar at T360. CONCLUSION: We conclude that hypodermoclysis of glucose-saline solution induced similar but smaller metabolic and hormonal changes than the IV infusion.

Analysis of the lipid content and the motility of human sperm after follicular fluid treatment.

The effect of human follicular fluid (hFF) on the cholesterol and phospholipid content and the movement characteristics of human spermatozoa were studied. Semen was selected by a discontinuous Percoll gradient and incubated during in vitro capacitating conditions with B2 medium supplemented with hFF 20%. Percoll pelleted spermatozoa were incubated in either B2 (B2-Percoll) or B2 supplemented with hFF (hFF-Percoll). In hFF-Percoll, we observed a time-dependent (24 h) decrease in both the cholesterol and phospholipid contents (cholesterol: 10.1 vs. 8.7 nmol 10(-7) spermatozoa; phospholipids: 17.5 vs. 15.7 nmol 10(-7) spermatozoa, P < 0.05). This decrease in cholesterol and phospholipids in human spermatozoa was concomitant with a high straight line velocity, a high progressive motility percentage and an increased value of lateral head displacement without any significant alteration of the spermatozoal membrane. No modification of the cholesterol: phospholipid ratio after 2 and 24 h of incubation in either B2-Percoll (0.61, 0.54) in hFF-Percoll (0.59, 0.63) was observed when compared with original control semen. It is suggested that the decrease in cholesterol and phospholipids in hFF-Percoll may be taken into account for the changes of membrane modification as part of the capacitation process.

Glucose oxidation after a peritoneal and an oral glucose load in dialyzed patients.

Glucose oxidation and thermogenesis were studied after a peritoneal (P) and an oral (O) glucose load in nine chronically uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 24.4 +/- 5.8 months. The O load (50 g) given was equivalent to the amount of glucose absorbed over six hours through the peritoneum of the subjects (51.7 +/- 3.3 g). Glucose oxidation and energy expenditure were obtained using indirect calorimetry in basal state and over the six hours following the glucose load. Glucose oxidation rate was higher from 60 to 180 minutes after O than after P (P < 0.05), with peak values of 3.85 +/- 0.28 mg.kg-1.min-1 and 2.80 +/- 0.17 mg.kg-1.min-1 respectively (P < 0.05). Cumulated glucose oxidation over six hours was 53.6 +/- 0.6 versus 47.0 +/- 3.4 g after O and P respectively (NS). Glucose-induced thermogenesis was 8.7 +/- 2.9% versus 5 +/- 1.9% after O and P, respectively (NS). The route of administration of glucose induces different kinetics of the glucose oxidation rate, but a similar amount of glucose absorbed either by the peritoneum or by the gut contributes in a similar extent to glucose and energy balance.

Treatment of human spermatozoa with follicular fluid can influence lipid content and motility during in vitro capacitation.

In order to evaluate the role of human follicular fluid (HFF) on the fertilizing capacity of spermatozoa, we studied the effect of HFF on the lipid composition and on the movement characteristics of human spermatozoa. Spermatozoa (spz) from normospermic patients were prepared with a discontinuous Percoll gradient and incubated in Ménézo B2 medium with or without a supplement of 20% HFF (HFF-Percoll spz and B2-Percoll spz respectively) for 2 and 24 h. After 2 h HFF incubation, percentage progressive motility, straight line velocity (VSL), and amplitude of lateral head displacement (ALH) were improved in HFF-Percoll spz as compared to B2-Percoll spz (P < or = 0.05). After a longer incubation period (24 h), lipid changes appeared in HFF-Percoll spz with lower levels of cholesterol (P = 0.02) and phospholipids (P = 0.05). No modification of the cholesterol/phospholipid ratio after 2 and 24 h of incubation in either B2-Percoll spz or HFF-Percoll spz was observed. Such decreases in lipid content of HFF-Percoll spz may be factors which could be taken into account as constituting part of membrane modifications during the capacitation process.

[Short-duration fatty meal loading for the assessment of intestinal malabsorption syndromes in children: preliminary study]. / Epreuve courte de charge orale en graisse pour l'exploration des syndromes de malabsorption intestinale chez l'enfant: étude préliminaire.

The determination of fecal fat gives a reliable index for studying fat intestinal absorption in children, but requires the collection of whole day stools for 3 consecutive days. To avoid stool collection constraint, the authors implemented a 3-point short-duration fatty meal test with determination of subsequent increase in serum levels of triglycerides and chylomicrons which then were compared to fasting values. Normal values were determined among control healthy children. Five patients with diagnosed malabsorption syndromes showed markedly impaired results. This fatty meal test seemed simple, easy to perform during a full-day admission. Further studies are being implemented to confirm its good diagnostic value.

[Comparison of plasma concentration and tolerance of a single dose of human calcitonin by intradermal and subcutaneous administration]. / Comparaison des concentrations plasmatiques et de la tolérance d'une dose unique de calcitonine humaine administrée par voie intradermique et sous-cutanée.

UNLABELLED: The aim of the study was to compare plasmatic levels of calcitonin obtained after intradermic (ID) and usual subcutaneous (SC) route of administration. METHOD: 6 volunteers between 18 and 40 years old received calcitonin 0.5 mg (Cibacalcin, Ciba-Geigy Laboratory) by ID and SC routes in a random order but at the same site of injection. Each administration was spaced by 8 days. Plasmatic levels were measured by R.I.A. before administration then 2 (M2), 7 (M7), 15 (M15), 30 (M30) minutes and 1 (H1), 2 (H2), 4 (H4), 8 (H8), 12 (H12) hours after each administration. RESULTS: Tmax were at 23.6 +/- 10 min and 16.2 +/- 7.5 min for SC and ID routes respectively. With ID route, Tmax was reached simultaneously or earlier (3 times). Cmax is significantly higher with ID route. Neither mean plasmatic levels at each plasmatic dosage nor mean areas under the curve between 0 to 1,440 min or between 0 to 480 min (this latest AUC calculate to minimize the importance of calcitonin basal level) were significantly different with ID and SC routes. 16 mild side effects (8 with each administration) were observed in 4 subjects. They appeared before 5 min. and were transient (1 hour) for cutaneous manifestations, and later between hours 3 and 7 for nausea and vomiting or asthenia. The mean lowering of calcemia was 0.29 +/- 0.21 and 0.18 +/- 0.11 mmol/l respectively for SC and ID route. In this study ID and SC routes for calcitonin administration are not different with regard to plasma levels and side effects.

[Changes in nutritional status at the initial phase of treatment of cancers and malignant hemopathies]. / Modifications de l'état nutritionnel à la phase initiale du traitement des cancers et des hémopathies malignes.

Changes in nutritional status at the initial phase of treatment of cancers and malignant blood diseases were evaluated in 32 male patients (mean age 58 +/- 18 years) examined during three 4-day stays in hospital (T0, T1, T2) at 2 months' interval. On the first day of each stay the following parameters were measured: food intake (kcal/day), weight (kg), squared height (m), fat mass (kg) obtained by measuring 4 skin folds and using Durnin's tables, brachial muscle area (cm2) and total skeletal muscle mass (kg) calculated from Heymsfield's equations. On the third and fourth days, after 48 hours of meat-free and fish-free diet, 3-methylhistidine (mmol/g creatininuria) and creatinine (mg) were measured in urine, and the urinary creatinine/height ratio (mg/cm/day) was calculated. Full anthropomorphic measurements were performed on 19/32 patients and complete measurements of 3-methylhistidine and the urinary creatinine/height ratio in 9/32 patients. Subsequent examinations revealed a decrease in brachial muscle area, total skeletal muscle mass and urinary creatinine/height ratio which, together with an increase in baseline 3-methylhistidine, confirmed the loss of muscle mass. Mean losses of muscle and fat were 6 p. 100 between T1 and T0 and 7 p. 100 between T2 and T0 for the muscle mass, and 9 p. 100 between T2 and T0 for the fat mass. These losses of body mass occurred very early, with significant differences between T1 and T0 and between T2 and T0. They suggest that protein-calorie malnutrition develops at a very early stage in patients treated for cancer or malignant blood disease.

[Anthropometric and biological evaluation of 44 patients with protein-calorie malnutrition]. / Evaluation anthropométrique et biologique de 44 patients présentant une malnutrition protéino-énergétique.

In industrial countries protein-calorie malnutrition (PCM) is a frequent cause of hospital morbidity and mortality. In this study, 88 hospital patients were evaluated: 44 (25 men and 19 women) aged from 20 to 80 years) with PCM, and 44 without malnutrition; the two groups were matched with regard to sex, age and height. The following parameters were determined: arm muscle surface, whole-body muscle mass, proportion of body fat, serum albumin (Alb), prealbumin (PA), retinol-binding protein (RBP), transferrin, thyroxine-binding protein, thyroxine, triiodothyronine, reverse triiodothyronine and total complement. Anthropometric measurements were validated by planimetry of a computerized tomographic section of the arm in 60 patients. There were significant differences between the two sexes in anthropometric values. Alb, PA and RBP values were different in men and RBP only in women; all other biochemical parameters were the same in both sexes. Thus, the group with PCM could be distinguished from the control group by anthropometric values and RBP values. Anthropometric parameters have been reported as being more specific of PCM than biochemical parameters, but since the latter are considered more sensitive, both complement each other and must be taken into account.

[Hypocaloric and high-protein diet in obese patients: changes in the lean mass]. / Régime hypocalorique et hyperprotidique chez l'obèse: variations de la masse maigre.

We have followed for 40 days seven hospitalized, young (age, mean SD : 33 +/- 8 yrs), and moderately obese (W/H : 35 +/- 3.92) women. During the first 5 days (DO to D5) they received a diet similar to their customary home-diet; from D6 to D40, their daily caloric intake was adjusted to 3,41 +/- 0.13 MJ (816 +/- 30 kcal). This diet comprised 21 p. 100 of sugars, 35 p. 100 of lipids, 1.57 +/- 0.09 g proteins per kg ideal body weight. Five seven-day periods have been studied. On the first day of each period, we recorded body weight and measured plasma albumin, pre albumin, retinol binding protein, complement (CH50 and C3) C peptide (in the fasting state and after glucagon stimulation), and thyroid hormones (T3 and rT3). On each of the 35 days of this study, total nitrogen was measured (Kjeldahl's method) in food, urine and faeces. On D0 and D41 lean and fat body masses were evaluated through measurements of total water (dilution of tritiated water) and of skin fold thickness respectively. From D0 to D40, the average weight loss was 8.76 +/- 1.86 kg; the cumulated nitrogen balances were negative in 6 patients and positive in one, with variations from one period to another and from one patient to another. Plasma proteins and hormones did not vary significantly. Changes in lean mass were comprised between + 0,7 and -- 1,6 kg in spite of the fact that all patients received the same caloric and protein intake.

Mathematical studies of complement activation.

Kinetic studies of complement activation were followed by hemolytic assay. Mathematical analysis shows that the curve is composed of two exponents: the first one, which occurs during a short span of time, represents the classical pathway, the second the alternative pathway. We were therefore able to foretell the respective participation of each activator used: inulin, zymosan, and aggregated immunoglobulins.