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Objective: Rapid undernutrition in patients with anorexia nervosa can compromise vital functions, notably due to cardiac complications. The aim of this study was to analyze the clinical parameters of anorexic patients, hospitalized for substantial weight loss, in a general pediatric inpatient unit, in order to determine which parameters should be tested by the medical doctor., Population and Methods: We performed a retrospective study on 20 consecutive patients (18 girls), median age of 13.75 (+/-2.3) years, admitted for the first time in our pediatric inpatient unit for anorexia nervosa., Results: Symptoms evolved for a median duration of 11.5 (+/-10.2) months before admittance and was shorter for the youngest patients (r = 0.42, p = 0.067). The mean BMI was 13.3 (+/-0.6) kg/m(2) (-3.0+/-1.2 Z-score) and was inversely correlated with serum creatinine levels (74+/-15 micromol/l) (r = 0.44, p < 0.05). The mean BMI variation between the beginning of the disease and hospitalization (Delta BMI) was-3.5 Z-score and was correlated to low systolic blood pressure (r = 0.45, p< or =0.05) and the presence of a pericardial effusion at admittance (r = 0.45, p < 0.05). Complete blood count, electrolyte balance and the serum phosphorus levels were normal except in 1 case. Mean serum glucose was 3.5+/-1.2 mmol/l. At admittance, an electrocardiogram, performed for 16 patients, showed sinusal bradycardia without conduction impairment. Enteral nutrition was necessary for 14 patients (70%) for a mean duration of 18.1 days (range, 6-56 days). The mean weight gain was 3.1+/-2 kg and was inversely correlated to the BMI at admittance (r = 0.49, p < 0.05)., Conclusion: Medical supervision of undernutrition tolerance during anorexia nervosa is above all clinical, as hematological and biological parameters remain normal for a long time. The cardiac complications found in our study appeared to be more related to the rapid rate of weight loss than to the amount of weight loss itself., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Insulin resistance is observed in several diseases such as non insulin dependent diabetes mellitus (NIDDM) or polycystic ovarian syndrome (PCOS). To understand genetic determinism of this abnormality we have developed a multidisciplinary approach including selection of phenotypes with insulin resistance confirmed in vivo by minimal model of Bergman and characterization of cellular defects in insulin action on circulating erythrocytes and monocytes. Exploration of variability in candidate genes by direct sequencing in some genetic syndromes of severe insulin resistance and acanthosis nigricans (mainly the Type A syndrome) revealed mutations of the insulin receptor gene associated with major defects in insulin binding or kinase activity. In other rare genetic syndromes or patients affected by NIDDM or PCOS defects appear to be located at post-receptor level, where IRS (insulin receptor substrate) genes are the most attractive candidates. Prevalence of some allelic variants suggested a potential role of IRS genes in insulin resistance, although their involvement in the pathogenesis of NIDDM remains controversial. Genotype-phenotype correlations in first degree relatives of an index case caring the Type A syndrome, suggested that association of allelic variants of IRS-1 and IRS-2 with insulin receptor mutations contribute, by synergistic effects, to phenotypic expression of defects in signal transduction. These mechanisms through genetic epistasis, involving several genes in insulin action, fit better with the polygenic nature of current forms of NIDDM and represent a good model in the study of pathogenesis of insulin resistance.

The authors describe the aggregation provoked on rat platelets using cumulative doses of ADP on the same sample. This model of aggregation is used to study the effects of three known aggregation inhibitors (aspirine, theophylline, isoproterenol) and one protease inhibitor, aprotinine.

As opposed to unique doses on different samples, cumulative doses of trypsin on the same rat platelet sample induced a monophasic and a more intense aggregation. Cumulative doses of trypsin were added in the presence of aprotinin, a protease inhibitor, and the curves drawn taking into account the amount of trypsin inhibited. In these conditions, the decrease of the maximum effect (Emax.) of trypsin, without change of the concentration inducing 50% of this maximum effect (EC50), suggests a non-competitive antagonism of trypsin by aprotinin on the mechanisms inducing platelet aggregation.

Desensitization of beta-adrenergic receptors means loss of receptor activity due to overstimulation by beta-mimetic drugs. Desensitization has been demonstrated in experimental studies using cell cultures, isolated organs and in vivo models. It generally evolves in two steps: uncoupling between the receptor and adenylate cyclase is followed by a decrease of the number (or down-regulation) of receptors. Desensitization can be either specific or non specific. In the first case, the phenomenon is related to the occupation of the receptor by an agonist and the occupied receptor only is altered (homologous desensitization). In the second case, the phenomenon is related to production in excess of cyclic AMP and other adenylate cyclase-coupled receptors are altered (heterologous desensitization). Studies performed on cellular models have shown that beta-receptor desensitization can be related to phosphorylation of the receptor by a cyclic AMP-dependent protein-kinase and that down-regulation corresponds to the incorporation of the beta-receptors in cytoplasmic vesicles. Desensitization has also been related to the activation of membrane phospholipid metabolism and the production of prostaglandins. Studies of bronchial beta-adrenergic receptors, mostly performed on isolated organs, have shown that beta-mimetic and, in some cases, phosphodiesterase inhibitor drugs can induce desensitization of beta-receptors. The possibility of beta-adrenergic receptor activity and desensitization independent of adenylate cyclase and cyclic AMP has also been evoked. In clinical practice, the reality of beta-adrenergic desensitization is still controversial. The existence of a variable proportion of "spare" receptors could explain the variability of patient responses to the long-term treatment of asthma by beta-mimetic drugs.