Arginine behaviour after arginine or citrulline administration in older subjects.

Arginine (ARG) and its precursor citrulline (CIT) are popular dietary supplements, especially for the elderly. However, age-related reductions in lean body mass and alterations in organ functions could change their bioavailability. Pharmacokinetics and tolerance to amino acid (AA) loads are poorly documented in elderly subjects. The objective here was to characterise the plasma kinetics of CIT and ARG in a single-dosing study design. Eight fasting elderly men underwent two separate isomolar oral loading tests (10 g of CIT or 9·94 g of ARG). Blood was withdrawn over an 8-h period to measure plasma AA concentrations. Only CIT, ornithine and ARG plasma concentrations were changed. Volume of distribution was not dependent on AA administered. Conversely, parameters related to ARG kinetics were strongly dependent on AA administered: after ARG load, elimination was higher (ARG>CIT; P=0·041) and admission period+time at peak concentration was lower (ARG

Cat sensitization according to cat window of exposure in adult asthmatics.

BACKGROUND: In adults, there is limited information on tolerance to cat, which may be reflected by high IgG4 without IgE sensitization. Early exposure to cat may play a critical role. OBJECTIVE: The aim was to assess among adults the association of Fel d 1 IgG4, Fel d 1 IgE, skin prick test (SPT) response to cat and pet-related symptoms in relation to exposure to cat considering the period of exposure. METHODS: SPT response to cat, specific IgE and IgG4 to Fel d 1 were assessed in 167 asthmatics recruited in chest clinics (40 years of age in average) from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Childhood and/or current exposure to cat were studied retrospectively. RESULTS: IgG4 was higher in relation to current cat exposure (0.53 vs. 0.09 ng/mL; P<0.001) and higher in women than in men. The period of cat exposure was significantly related to Fel d 1 IgE, the IgE/IgG4 pattern and cat weal size. The lowest values of Fel d 1 IgE, cat weal size, pet-related nasal or respiratory symptoms were observed in those with both childhood and current exposure as well as the highest proportion of the IgE-/IgG4+ pattern observed in 1.4%, 4.0%, 38.1% and 12.5% of those with -/-, +/-, +/+, -/+ childhood/current exposure, respectively. CONCLUSIONS: Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG4 and low IgE. Continuous exposure may maintain a state of immunological tolerance to cat.

[Environmental factors for asthma severity and allergy: results from the EGEA study]. / Facteurs environnementaux de l'asthme sévère et de l'allergie: résultats de l'étude EGEA.

INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.

Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France.

OBJECTIVE: To estimate the statistical distribution of the incubation period of Creutzfeldt-Jakob disease (CJD) in human growth hormone (hGH) recipients in France. BACKGROUND: Published papers suggest that the median incubation period of hGH-related CJD is approximately 15 years, but there are as yet no statistical data that support this assertion. METHODS: Of the 1,361 hGH recipients who were included in this study, 55 had developed CJD at the time of the study. Individual data on hGH treatment history were available. Different mathematical models were used to estimate the statistical distribution of the incubation period. One main feature of the models was to take into account the occurrence of future CJD cases. RESULTS: Models showed that the mean incubation period was 9 to 10 years, and the 95th percentile of the distribution was 15 to 16 years. Data and models indicated that the incubation period was significantly shorter in homozygotes at codon 129 of the prion protein gene than in heterozygotes. CONCLUSIONS: The short mean incubation period of CJD in French hGH recipients may be due to high infectivity in hormone lots. Estimates of the 95th percentile indicate that the number of hGH-related CJD cases may continue to increase in the coming years.

Distributions of hand preference and hand skill asymmetry in preschool children: theoretical implications.

We describe the distributions of hand skill asymmetry for the Peg-moving task and the Graphic test among 765 preschool children. A single normal component was observed for the Peg-moving task, but two normal components for the Graphic test, which corresponded primarily to the right- and left-handed children. Hand Preference and Graphic test hand skill asymmetry were age-dependent, but there was no age effect on the PMT hand skill asymmetry. Results are discussed in relation to the Annett's Right Shift theory.

Modelling the annual risk of tuberculosis infection.

BACKGROUND: Tuberculosis has been declining in developed countries for a long time, as a result of the intrinsic epidemiological characteristics of this disease, combined with improvement in the standard of living and more recently the use of antibiotics. In these low prevalence countries, decisions concerning the objectives of tuberculosis programmes have to be taken and the consequences of short term changes in the sanitary situation have to be assessed. METHODS: A deterministic model, without age structure, of the dynamics of pulmonary tuberculosis is proposed. The model extends that of Waaler and is intended to be more suitable for application to developed countries. The flows between seven subgroups of population, based on the natural history of the disease, are modelled and vaccination is taken into account. Values of model parameters and initial prevalences were deduced from published data. RESULTS: As a first step, qualitative comparisons are performed between the model-predicted decline in the annual risk of infection (ARI) and data from the Netherlands tuberculosis survey. Using parameter values suited to France, our model shows that the predicted decline is slower in France than in the Netherlands; a result which tallies with epidemiological observations. Uses of the model as a decision tool are illustrated in two cases, that of ending systematic BCG vaccination and that of a sudden increase in the number of infectious cases.

Evaluation of the degree of desialylation of serum alpha 1-acid glycoprotein and alpha 1-antitrypsin.

A method for evaluating the degree of desialylation of alpha 1-AGP and alpha 1-AT has been developed. It consists in their simultaneous determination by radial immunodiffusion (RID) and electroimmunodiffusion (EID). When a desialylation exists, an underestimation by EID relative to RID is found. (1) No significant desialylation of alpha 1-AGP and alpha 1-AT occurred in normal subjects. (2) No correlation between desialylation of alpha 1-AGP and alpha 1-AT and their amounts existed. (3) Desialylation was preferentially observed in patients with severe hepatic damage but also with inflammatory disorders.

Assessment of the global two-stage method to EC50 determination.

Preclinical studies of a new drug supply sets of concentration-effect observations. For each experiment, EC50 is estimated through fitting of the Emax model. Naive pooling of these individual estimates, also called the Standard Two-Stage method (STS), is usually performed. A better combination is obtained by the Global Two-Stage method (GTS) which takes into account the variability of the nonlinear regression estimation errors. The performances of STS and GTS are compared on real and simulated data. The results show that GTS performs better than STS in terms of bias or RMSE, especially in case of poorly designed experiments. Degradation of the quality of STS results in simulations appears to be mainly due to some experiments that are usually rejected by experimenters. Such rejections are avoided when using GTS, which hence is particularly suitable for systematic treatment of this kind of data.

Lipogenesis from U14C lactate in obese Zucker rat hepatocytes. Effect of albumin-bound oleate.

Lipogenesis from U(14C) lactate was studied in hepatocytes isolated from obese Zucker rats (fa/fa) their lean littermates (Fa/?) and Sprague Dawley rats. The distribution of radioactive carbon between the glycerol and the fatty acid moieties of the acylglycerols were studied. Radioactive lactate was better utilized for glycerol formation than it was for fatty acid formation in the obese rats. However, when oleate was added to the hepatocytic incubation medium, radioactive lactate was preferentially incorporated into the fatty acid moiety of the acylglycerols. Zucker obesity classified as a "metabolic obesity" by Meyer (1) depends upon abnormalities in carbohydrate metabolism associated with increased lipogenesis. This might be explained by biochemical shifts in the utilization of nutrients (2). Among the nutrients, lactate seems to be a better source of carbon than glucose for lipid synthesis (3). It has been shown that there is an increased hepatic portal blood concentration of lactate several hours after eating: about 4 mM in Wistar rats (4) and 10-15 mM in obese Zucker rats (3). We are interested in determinating the incorporation of carbon from lactate either into glycerol or into fatty acyl moieties of hepatic acylglycerols, and in determining the influence of exogenous fatty acids on acylglycerol synthesis, since a high level of circulating fatty acids in Zucker obese rats has been reported (5). Our purpose was to determine the incorporation of lactate into glycerol and fatty acyl moieties of acylglycerols, under the influence of oleate. Hepatocytes were isolated from ad libitum fed obese Zucker rats (fa/fa), their lean littermates (Fa/?) and Sprague-Dawley rats (SD). Incorporation of lactate was studied for three hours, in order to exclude short-term regulation effects and to allow oleate to be distributed into all cellular compartments.

Permutation distribution estimation applied to the comparison of the profile of the activity of two antianginal drugs.

The comparison of the anti-ischemic activity of trimetazidine and propranolol was evaluated by multiple end points (clinical, exercise test, and ambulatory electrocardiogram [ECG] monitoring criteria) in 149 male patients with effort angina who received either trimetazidine 20 mg tid or propranolol 40 mg tid during a period of 3 months. The distribution of the standardized differences between the two treatments for each variable was obtained by a permutation method. The medians (estimation of the actual difference between the two treatments) and the 5, 25, 75 and 95% quantiles were represented on the same diagram for all end points. The pattern of the standardized distribution of the differences showed a similar activity of both drugs on symptoms and nitrates consumption, on exercise tolerance and increase in ischemic threshold at exercise, and on ischemia recorded at ambulatory ECG monitoring. Conversely, only propranolol decreased heart rate and rate pressure product at rest as well as at exercise, underlining the difference in the mode of action of the two drugs. This descriptive technique is an attractive method to evaluate the differences between drugs considering multiple criteria favouring the estimation of these differences together with their variability.

A three-state Markov model of Plasmodium falciparum parasitemia.

A three-state Markov model taking into account clinical signs of malaria infections by P. falciparum is described. The three states considered are the noninfected (state 0), the infected exhibiting no clinical signs (state 1), and the infected with clinical signs (state 2). Methods for estimating the transition rates from longitudinal data are indicated. This model was used to assess the effect on children of an intervention trial on the use of mosquito nets impregnated with insecticide. The trial was conducted in West Africa (Burkina Faso) between 1985 and 1987. The analysis showed that the intervention was most effective on transition rates between state 1 and state 2.

[Comparison of 14 methods for analysing left ventricle segmental kinetics by cineangiography]. / Comparaison de 14 méthodes d'analyse de la cinétique segmentaire du ventricule gauche par cinéangiographie.

Fourteen methods of analysing left ventricular wall motion on 30 degrees right anterior oblique left ventricular cineangiography were compared in 70 cases using a HP 9845 B computer. The methods included the superposition of the centres of gravity, perpendicular to the long axis, Leighton's Rickard 's, Ingels ' and others to determine the influence of the use of different anatomical points of reference on the results. A score was given for each programme in comparison with three groups of normal angiography, anterior infarction and inferior infarction limited to a single zone with no lesion on the opposite coronary artery. The score was the ratio of radial shortening of normal wall motion to that of the infarcted wall. The fourteen methods were divided into 4 groups according to the type of infarct studied (anterior or inferior) and according to the use of either percentage radial shortening or the ratio of the surfaces described by these radii and the systolic and diastolic contours. The results underlined the importance of the anatomical references : aortic orifice and apex for centering systolic and diastolic contours. The methods which did not take these factors into account or which did not correct for them in diastole and systole gave poor results. The centre of gravity of the systolic contour was also an unreliable reference point. The three methods which gave the best results, independent of the site of infarction or the method of calculation (ratio of the radii or surfaces) were all based on the long axis from the aortic orifice to the apex.(ABSTRACT TRUNCATED AT 250 WORDS)

[Structural relations in the comparison of methods in clinical chemistry. Application to the study of bias between a centrifugal analysis (Cobas) and the Kodak-Ektachem method]. / La relation structurale dans la comparaison de méthodes en chimie clinique. Application à l'étude du biais entre une analyse centrifuge (Cobas) et le procédé Kodak-Ektachem.

In this paper, the authors present the aims of a comparison of 2 biochemical methods in terms of their accuracy. They discuss the inadequacies of classical statistical techniques (paired series, linear correlation coefficient, regression). Instead of them, the authors suggest other approaches based on the structural relationship and, more particularly, York's method which, at the present time, seems to be the best one adapted to the most frequently encountered experimental conditions. They illustrate their view by a study of bias between centrifuge analysis (Cobas) and the Kodak-Ektachem process in plasma calcium assay.

Estimation of the proportion of genetic cases in late-onset diseases: an application to Alzheimer's disease.

In diseases with a complex etiology including a genetic component, an important issue is to determine the proportion of cases really having inherited the disease. This is not easy in late-onset diseases where censoring might obscure the transmission pattern of the disease and give an apparently non-genetic distribution of the cases. We present a model that allows the estimation of the proportion of genetic cases in late-onset diseases. This model takes censoring into account by explicit modelling of the time dependency of the onset of the disease. The model is illustrated with an example based on an epidemiological survey in Alzheimer's disease and with simulated data.

Is dementia of the Alzheimer type a purely genetic illness? A modelling approach.

In some multiple-case families, dementia of the Alzheimer type (DAT) is very likely to be of a genetic origin. Nevertheless, most DAT cases are sporadic and a disease with a majority of sporadic cases is usually of environmental origin. Are there two different etiologies of DAT? And if so, what is the proportion of genetic cases? We describe a model designed to assess the genetic risk in DAT. Our basic hypotheses were: (1) DAT could be of either genetic or environmental origin; (2) in its genetic form, transmission is of the autosomal dominant type, and (3) a proportion (pi) of the population is exposed to environmental risk. We have estimated the value of the probability (pi) of being exposed to the environmental risk and of the gene frequency (p). These values were highly dependent on the model assumptions, but non-inherited cases were consistently more frequent than inherited ones.

The protective role of country living on skin prick tests, immunoglobulin E and asthma in adults from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy.

BACKGROUND: Farming environment and traditional lifestyle seem to protect from childhood allergy. OBJECTIVE: The aim is to analyse the relationships of living in the country to asthma, positive skin prick tests and IgE among adults considering various windows of exposure over the life-span. METHODS: The study concerns 805 adults drawn from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA) (asthmatic cases, non-asthmatic controls, and parents of cases with and without asthma). Ever living in the country concerned 55% of the subjects. Early (beginning < 1 years), childhood (beginning < or = 16 years), prolonged (duration > or = 10 years) and current life in the country were studied. RESULTS: The results based on the case control and family components of the study show that IgE levels were significantly lower in those who ever lived in the country and in particular in those who lived for > or = 10 years. Positive skin prick tests (SPT) were significantly less prevalent in those who ever lived in the country and in particular in those with childhood (< or = 16 years) exposure. These associations remained independent of age, sex, smoking or asthma with IgE levels of 64 vs. 88 IU/mL; P = 0.004 for those ever living in the country vs. others and odds ratio for SPT positivity of 0.72 (95% CI [0.53-0.98]). In the more specific group with traditional mode of heating in childhood (use of wood) associations were stronger. The association with asthma, studied in parents of asthmatic probands showed that fathers, but not mothers, of asthmatics were significantly less often asthmatic themselves in relation to country living. CONCLUSION: Country life protects from asthma and adulthood allergy. The protective effect is not restricted to exposure in early childhood.