Congenital hyperinsulinism: current trends in diagnosis and therapy

Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Utilisation de l'instabilité des microsatellites et de l'immunohistochimie dans le dépistage du syndrome HNPCC [hereditary non polyposis colorectal cancer] (résultats préliminaires)

Les syndromes HNPCC posent le problème de leur reconnaissance au sein de l'ensemble des cancers colorectaux sporadiques. L'intérêt du dépistage des familles HNPCC est bien établi. La recherche d'une mutation des gènes impliqués dans ce syndrome doit être réservée à un sous-groupe de patients susceptibles d'en être porteurs. La recherche d'instabilité des microsatellites ou la réalisation d'une immunohistochimie semble représenter un bon outil d'aide diagnostique. Le but de notre travail était d'étudier, de façon prospective, l'intérêt de ces deux tests biologiques, sur des cancers colorectaux de patients suspects de syndrome HNPCC. Des familles étaient sélectionnées sur des critères cliniques et réparties dans 5 différents sous-groupes. Une recherche de mutation des gènes hMLH1 et hMSH2 était réalisée parallèlement à la réalisation d'une immunohistochimie des protéines correspondantes et d'un test RER. Nos résultats confirmaient une bonne corrélation entre la perte d'expression protéique et la présence d'un phénotype instable. Par contre, ces tests ne permettaient pas de prédire certaines des mutations retrouvées sur le gène hMLH1. Pour sélectionner les sujets atteints d'une mutation MMR, les valeurs prédictives positives et négatives de l'immunohistochimie étaient supérieures à celles du test RER. Ces résultats nécessitent confirmation sur un plus grand effectif. Cependant, cette étude nous incite à la plus grande prudence dans l'interprétation des résultats de ces tests, tout particulièrement lorsque les critères cliniques sont très évocateurs de syndrome HNPCC.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Essai de caractérisation phytoécologique des formations herbacées pâturées de Grande-Terre (Guadeloupe)

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FACTEURS PREDICTIFS DE BONNE REPONSE A LA DILATATION PNEUMATIQUE DANS L'ACHALASIE PRIMITIVE

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Sympathetic Control of Lower Esophageal Sphincter Function in the Cat: ACTION OF DIRECT CERVICAL AND SPLANCHNIC NERVE STIMULATION

The purpose of this study was to determine the effect of direct stimulation of the sympathetic nerves on the lower esophageal sphincter (LES) in the anesthetized cat. Neither unilateral nor bilateral cervical sympathectomy, or splanchnicectomy significantly modified basal LES pressure in animals with intact vagi, or animals having undergone bilateral cervical vagotomy. Electrical stimulation of the cut, peripheral, cervical sympathetic trunk increased mean arterial blood pressure, but had no effect on LES pressure or LES relaxation as induced by vagal stimulation. Stimulation of the central end of the cervical sympathetic trunk had no effect on LES pressure. Stimulation of the central end of the cut splanchnic nerve produced a decrease in LES pressure with a maximal response of 69.1±16.0% (mean±SEM). This inhibitory response was not modified by either propranolol or bilateral cervical vagotomy. Stimulation of the peripheral end of the cut, greater splanchnic nerve gave an increase in LES pressure with a maximal response of 38.2±7.19 mm Hg. Guanethidine, in the presence or absence of the adrenal glands, significantly augmented this excitatory response. This response was also slightly increased by phentolamine alone at 10 V, 1 Hz, but was not altered by propranolol. The excitatory response was completely antagonized by atropine or by trimethaphan camsylate. Stimulation of the peripheral end of the splanchnic nerve inhibited LES relaxation as induced by vagal stimulation. The results of this study suggest that: (a) the LES in the cat is not affected by either central or peripheral stimulation of the cervical sympathetic trunk; (b) the central portion of the splanchnic nerve carries an afferent inhibitory response to the LES through yet unknown pathways; (c) the peripheral splanchnic nerve carries an atropine-sensitive excitatory response to the LES; and (d) the splanchnic nerves may modulate LES relaxation as induced by vagal stimulation

Radar differential reflectivity ZDR : a real-case evaluation of errors induced by antenna characteristics

International audienceMultiple parameter radar measurements (dual frequency hail signal DFR-HS or differential reflectivity ZDR) can be strongly affected by the mismatch of the antenna illumination functions at the two wavelengths or polarizations. The resulting instrumental error can be estimated, with some approximations, from the independently measured reflectivity at one wavelength or polarization by using the actual radar illumination functions. This objective estimation of the antenna-induced error is made in some real cases and its possible conseqences on the data analysis are discussed

Civilisations en transition (III). Sociétés multiconfessionnelles à travers l'histoire du Proche-Orient. Actes du colloque scientifique international, 7-8-9 septembre 2016

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