Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mercredi 22 novembre 2017

Le dépistage néonatal de la drépanocytose, maladie génétique la plus fréquente en France, permet un diagnostic précoce de toutes les formes de syndromes drépanocytaires majeurs (homozygote S, hétérozygote composite S/bêta-thalassémie ou S/C). Il est réalisé à partir d’un prélèvement sur papier buvard avec une première technique de chromatographie liquide haute performance et confirmé, dans le cas d’une anomalie, par une deuxième technique de type électrophorétique (ou inversement). Le dépistage néonatal n’est utile que lorsqu’il s’inscrit dans un système de soin organisé pour la prise en charge efficace des enfants atteints. Nous avons réalisé une évaluation rétrospective (1995-2009) des enfants atteints de drépanocytose diagnostiqués par le dépistage néonatal et suivis dans les hôpitaux de la région Nord-Francilienne. Nous avons recueilli le devenir des patients, la prise en charge et son adéquation avec les recommandations nationales publiées en 2005. L’efficacité du dépistage pour initier un traitement est très efficace puisque 98,7% des malades commencent un suivi à un âge moyen de 2 mois. Les résultats de 1 033 patients avec 6776 années-patient de suivi, dont 742 sont SS/Sβ0thal, ont été analysés. La moyenne d’âge de la cohorte est de 7,1 ± 3,9 ans. Dix-sept patients sont décédés à un âge moyen de 14,9 mois (rang 0,23-89 mois)avec 13 décès en rapport avec la drépanocytose observés uniquement chez des patients SS. Au total la survie des patients SS/Sβ0thal est de 97,1% à 15,8 ans (intervalle de confiance à 95% de 95,2 à 98,3%). Dans la cohorte, la stratégie préventive est appliquée selon les recommandations. Tous les patients bénéficient de l’antibioprophylaxie avec respect du schéma vaccinal strict pour 81% des patients. Le risque cumulatif d’accident vasculaire cérébral est de 0,25 (0,11-0,39) pour 100 années-patient. La grande majorité des patients (97,3%) avec une échographie transcrânienne ont une intensification thérapeutique adaptée. Cette analyse rétrospective montre l’efficacité de la prise en charge d’un nouveau patient drépanocytaire dépisté. C’est une étape préalable nécessaire à la mise en place de mesures correctives.Neonatal screening for sickle cell disease (SCD), the most common of recessive autosomic hemoglobin disorders, allows detection of affected babies (homozygous sickle cell disease, compound heterozygote SC, and S b-thalassemia) in a target population. A dry blood sample is obtained by heel stick and analyzed by high-performance liquid chromatography as a first-line method, followed by isoelectric focusing for confirmation, whenever a variant haemoglobin is observed on first-line method. Screening is only a component of a comprehensive system of care, including medical care. We conducted a retrospective evaluation (1995-2009) of SCD newborns outcome followed in a multicenter hospital-based network between a referral center and local specialized teams in the Northern Area of Paris. We evaluated patient's outcomes, medical care, and its adequacy to national guidelines published since 2005. Initial retrieval of SCD babies diagnosed through newborn screening was very efficient with 98.7% starting follow-up at a median age of 2 months. Data from 1 033 subjects with 6 776 patient-years of follow-up were analyzed among whom 742 had SS or Sβ0 thalassemia. Mean age of the cohort is 7.1 ± 3.9 years. Seventeen patients died at a median age 14.9 months (range 0.23-89) with 13 SCD related deaths at a median age of 23 months (range 5.5-89), all with sickle cell anemia (SS). Overall survival in SS/Sb0 patients was 97.1% at 15.8 years (95%IC : [95.2 ; 98.3]). In the cohort, preventive strategy was applied as recommended. All patients were under Peni V prophylaxis with 81% of long term optimal schedule of pneumococcal immunization. The cumulative risk of overt stroke was 0.25 per 100 patient years (0.11 ; 0.39). 97.3% of the patients with abnormal TCD have correct intensification therapy. The good results on SCD mortality and morbidity could be improved in this recently immigrated population by programs combining a territorial team with educated multi-ethnic staff and web-conferences on all at risk patients between referral center and local teams.

Background. - Leser-Trelat sign involves the combined sudden onset of seborrheic keratosis and cancer. However, some doubt surrounds the existence of this syndrome. We report a case of Leser-Trelat sign that led to the discovery of Sezary syndrome.Patients and methods. - A 59-year-old woman presented generalized pruritus with secondary appearance of multiple seborrheic keratosis. Leser-Trelat sign was diagnosed and 20 months later, Sezary syndrome was discovered. Extracorporeal photopheresis was initiated, after which there was a marked reduction in the patient's pruritus, erythroderma and numbers of seborrheic keratoses and Sezary. cells.Discussion. - Leser-Trelat sign is often associated with gastric carcinoma or lymphoproliferative tumours. Rampen and Schwengle [J Am Acad Dermatol 21 (1989) 50-5] have thrown doubt on this entity because of the "subjective" definition, the frequent dissociation between the course of the tumour and that of the seborrheic keratosis, the disparity between the frequency with which rapid onset seborrheic keratosis is seen and the rarity of cases in which this phenomenon reveals a tumour and the absence of association with any specific type of malignancy. The time between diagnosis of Sezary syndrome and cutaneous symptoms of Leser-Trelat sign appears very tong in the present case. In the absence of any established physiopathology, it is impossible to prove any direct link between these two syndromes.Leser-Trelat sign remains controversial. Knowledge of its pathogenesis could help determine whether Leser-Trelat sign should or should not be considered a paraneoplastic syndrome. (C) 2008 Elsevier Masson SAS. Tous droits reserves.

Several studies have demonstrated the beneficial role of functional tongue therapy in stabilizing treatments for dental malocclusion and treating sleep-disordered breathing (SDB). The aim of this retrospective study was to evaluate the effect on the upper airways of the Tongue Right Positioner device (TRP) used for the correction of atypical swallowing. We analyzed lateral headfilms of 94 orthodontic patients aged between 11 and 17, before the start of treatment and after establishment of mature swallowing, treated with the TRP (TRP group) or by reeducation exercises (control group). In the TRP group, the establishment of mature swallowing occurs twice as fast as in the control group. This led to thinning of the floor of the mouth (–8.38%, P < 0.001) linked to anteroposterior enlargement of the pharynx (+10.48%, P < 0.01), both probably due to an increase in genioglossal and styloglossal muscle tone and correction of cranio-cervical posture (+2.52%, P < 0.01). These results are not dependent on the type of orthodontic treatment. They suggest that the TRP could be used in the treatment of SDB.

16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure.Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV.Beyond the 16p11.2-related mirror effect on global brain morphometry, we observe regional mirror differences in the insula (deletion > control > duplication). Other regions are preferentially affected by either the deletion or the duplication: the calcarine cortex and transverse temporal gyrus (deletion > control; Cohen’s d > 1), the superior and middle temporal gyri (deletion < control; Cohen’s d < −1), and the caudate and hippocampus (control > duplication; −0.5 > Cohen’s d > −1). Measures of cognition, language, and social responsiveness and the presence of psychiatric diagnoses do not influence these results.The global and regional effects on brain morphometry due to 16p11.2 CNVs generalize across site, computational method, age, and sex. Effect sizes on neuroimaging and cognitive traits are comparable. Findings partially overlap with results of meta-analyses performed across psychiatric disorders. However, the lack of correlation between morphometric and clinical measures suggests that CNV-associated brain changes contribute to clinical manifestations but require additional factors for the development of the disorder. These findings highlight the power of genetic risk factors as a complement to studying groups defined by behavioral criteria.

Propos. – Le déficit immunitaire commun variable (DICV) regroupe des patients atteints d'un désordre immunitaire qui s'exprime par un défaut primaire de synthèse des immunoglobulines. Si les manifestations cliniques révélatrices du DICV sont dominées par des infections des voies aériennes supérieures, d'autres événements cliniques plus originaux existent comme des affections auto-immunes ou une granulomatose évocatrice de sarcoïdose.Méthodes. – Il s'agit d'une étude rétrospective portant sur 17 patients répondant à la définition du DICV. Parmi eux, 12 ont eu une étude de leurs sous-populations lymphocytaires avec expression de l'HLA-DR, marqueur d'activation des lymphocytes T.Résultats. – Il s'agit de 17 patients, 7 hommes et 10 femmes. L'âge moyen de début des symptômes est de 23 ans et l'âge moyen au moment du diagnostic est de 39 ans. Tous les patients décrivent des infections à répétition (principalement des infections des voies aériennes supérieures et des pneumopathies). Une malade présente une mycobactériose digestive. Les autres événements digestifs sont dominés par des diarrhées chroniques en rapport avec une atrophie villositaire, une giardiase ou une hyperplasie nodulaire lymphoïde. Sept malades présentent des manifestations auto-immunes (diabète insulinodépendant, purpura thrombopénique idiopathique, polyarthrite rhumatoïde) et 7 ont une splénomégalie. Trois patients ont une granulomatose diagnostiquée sur une pièce de splénectomie ou une biopsie ganglionnaire. Dix patients ont une lymphopénie T, 2 une lymphopénie B, 5 ont un rapport CD4/CD8 < 1 et 6 ont un taux de lymphocytes T CD4+ < 400/mm3. Parmi les 12 patients chez lesquels l'expression du marqueur d'activation lymphocytaire T HLA-DR a été recherchée, 7 ont des lymphocytes T activés sur les lymphocytes T CD4+ et/ou CD8+ et sont atteints soit d'une pathologie auto-immune soit d'un syndrome tumoral (splénomégalie ± adénopathies). Les 5 autres malades n'ont pas d'activation lymphocytaire et ne présentent que des manifestations infectieuses.Conclusions. – Notre travail permet de distinguer 2 groupes de patients avec un DICV selon le degré d'activation lymphocytaire T. Une classification de ces malades est utile pour définir des groupes homogènes permettant de réaliser des études fonctionnelles et génétiques qui devraient conduire à la découverte de défauts moléculaires hétérogènes.Purpose. – Common variable immunodeficiency (CVID) is an immune defect characterized by primary hypogammaglobulinemia. Most of the time, clinical manifestations that reveal CVID are recurrent bacterial infections, but auto-immune or granulomatous events may occur.Methods. – This retrospective study was conducted on 17 patients fulfilling the classical CVID definition. Lymphocyte activation level was evaluated in 12 patients through HLA-DR expression on lymphocytes subsets.Results. – This study includes 17 patients, 7 men and 10 women. The mean age at the first clinical manifestation is 23 years and the mean age at diagnosis is 39 years. Recurrent upper and lower bacterial respiratory tract infections are common to all patients. Abdominal infection due to Mycobacterium avium-intracellulare complex is found in one patient. Digestive events are dominated by chronic diarrhea caused by giardiasis, nodular lymphoid hyperplasia or villous atrophy. Seven patients developed auto-immune conditions (insulindependent diabetes, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis) and 7 patients have a splenomegaly. Non caseating granulomas in the spleen or in lymphnode biopsies are found in 3 patients. Ten patients have a T lymphopenia, 2 have a B lymphopenia, 5 have a CD4/CD8 ratio <1, and 6 have T CD4+ lymphocytes <400/mm3. The study of HLA-DR expression on lymphocytes subsets shows that 7/12 patients have activated T CD4+ and/or CD8+ cells and these patients have auto-immune or tumoral manifestations. The other 5 patients do not have activated T lymphocytes but present with infectious events only.Conclusions. – Our study allows the separation of patients with CVID according to their T lymphocytes activation level. A patient's classification is necessary to define homogeneous groups of patients to perform genetic and functional studies which will probably reveal heterogeneous molecular abnormalities.

Il n'existe aucune recommandation sur la prévention des thromboses rénovasculaires après transplantations rénales. Nous avons enquêté sur les pratiques cliniques.Dans 29 centres hospitaliers universitaires (CHU), le praticien référent en transplantation a été interrogé sur la thromboprophylaxie utilisée dans quatre cas cliniques de risque thrombotique croissant. No 1 : Homme jeune, sans facteur de risque thrombotique ou cardiovasculaire. Néphropathie à Ig A. Hémodialysé (HD). No 2 : Homme, 53 ans. Antécédent de phlébite. Glomérulonéphrite extramembraneuse (GEM) idiopathique. HD. No 3 : Homme, 58 ans. Cardiopathie ischémique. Néphroangiosclérose et diabète. En dialyse péritonéale (DP). Sous aspirine. No 4 : Femme, 63 ans. Tachyarythmie par fibrillation auriculaire (ACFA) sous antivitamine K (AVK). Néphropathie lupique sans syndrome des antiphospholipides (APL). HD.Cas no 1 : Aucune prophylaxie médicamenteuse (62 %), héparine calcique isocoagulante (34,5 %), héparine non fractionnée (HNF) isocoagulante (3,5 %). Cas no 2 : Pas de prophylaxie (38 %), héparine calcique isocoagulante (44,8 %), HNF isocoagulante (6,9 %), héparine de bas poids moléculaire (HBPM) (3,4 %). Cas no 3 : 62% arrêtaient l'aspirine dont 22% sans relais, 55 % avec un relais par héparine calcique isocoagulante et 11,1 % une HNF isocoagulante. Trente-huit pour cent poursuivaient l'aspirine dont 63,6 % sans autre prophylaxie, 27,3 % en associant une héparine calcique isocoagulante, et 9,1 % avec une HNF isocoagulante. Cas no 4 : HNF hypocoagulante (62 %), HNF isocoagulante (17,2 %), héparine calcique isocoagulante (13,8 %), héparine calcique hypocoagulante (6,9 %).Les pratiques sont hétérogènes entre les CHU pour des situations similaires. Elles relèvent plus d'habitudes locales que de pratiques évaluées. Une réflexion sur des recommandations dans la prévention des risques thrombotiques et hémorragique après transplantation rénale semble utile.Graft thrombosis is a major complication of transplantation. However, there are no recommendation on immediate postoperative thromboprophylaxis after kidney transplantation. We recorded clinical practices in France.In 29 transplantation centres, four case studies were submitted to the medical kidney transplantation referent (compatible graft from cadaveric donor, without perioperative complication). No 1: Man, 27-years-old, IgA glomerulonephritis, without history of hypercoagulability or cardiovascular risk factor. Hemodialysis since 12 months. No 2: Man, 53-years-old, with history of deep venous thrombosis after cholecystectomy 15 years before. Membranous nephropathy. Hemodialysis since 10 months. No 3: Man, 58-years-old, with history of myocardial infarction. On aspirin therapy. Nephroangiosclerosis and diabetic nephropathy. Peritoneal dialysis since 6 months. No 4: Woman, 63-years-old. Atrial fibrillation on vitamin K antagonists therapy. Lupus nephritis without antiphospholipid syndrome. Hemodialysis since 12 months.No 1: No anticoagulation therapy (62%), calcium heparin at prophylactic doses (34.5%). No 2: No anticoagulation therapy (38%), calcium heparin at prophylactic doses (44.8%). No 3: 62% interrupted aspirin of whom 22% without any immediate anticoagulation and 55% replaced aspirin with calcium heparin at prophylactic doses. Thirty-eight percent carried on with aspirin of whom 63.6% without other prophylaxis and 27.3% in association with calcium heparin at prophylactic doses. No 4: Unfractionned heparin at curative dose (62%), unfractionned heparin at prophylactic doses (17.2%), calcium heparin at prophylactic doses (13.8%).Postoperative anticoagulation after renal transplantation is established as a local dogma rather than evidence-based medicine. Guideline recommendations and standardized protocols for the use of anticoagulation after kidney transplantation should be developed.

In the field of thyroid disease, a number of governmental organisms or professional associations have published practice guidelines containing laboratory-related recommendations, eg the Haute autorité de la santé (HAS), or the American Thyroid Association (ATA). Among the physicians who prescribe thyroid function tests, all have not read and memorized all these recommendations. In order to help them to better integrate these recommendations in their practice, we have composed a thesaurus of ready-made interpretative comments, trying to adapt our proposed comments to each possible combination of results of TSH and/or free T4 and/or free T3. The laboratorians who would prefer to use only the comments based strictly on the recommendations of HAS and/or ATA, will be able to select among our comments what is really validated by these two organizations. In addition, our work aims at enabling the patients who want it, to benefit from written information, which may be complementary to the more often spoken information provided by the clinicians.

A summary of the measurements of the QCD colour factors at LEP is presented. Such measurements provide a test of the gauge group structure underlying the theory of strong interactions. A variety of methods have been applied by the various experiments, and perfect consistency with the expectation of QCD with SU(3) as gauge group is found. By translating a colour factor measurement into a determination of the number of active flavours, ALEPH exludes a light gluino for masses below 6.3 GeV/c2.

OBJECTIVES:The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM).PATIENTS AND METHOD:Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment.RESULTS:85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline).CONCLUSIONS:Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

P-533 Abstract: To improve operational perfomance in a modern navy force. the increasing use of different radiofrequency (RF) and microwaves emitting devices is largely observed by using up to date high power electromagnetic generating facilities. Modern radars use wideband frequencies and pulsed mode emission. As uses have multiplied and power output has become greater. exposures to microwave energy both at work and in daily life have increased. The health implicationon hazards of exposure of man to this type of non-ionizing radiation remain a matter of concern and uncertainty. The nature of biologic effect and the levels of microwaves in man are unclear. particulary with respect to long-term effects. It has been suggested that exposure to radiofrequency/microwaves radiations could be associated with greater health hazards and higher mortality. The all-cause mortality of 39.488 navy personnel of the French navy forces who served from 1975 until 1995 was studied over the period 1975–2001. A control group was formed by 13.217 militaries who served during the same period in the same military area but who were never exposed to radars. Administrative procedures for identifying militaries and their vital status were equivalent in the radar and the control groups. The age-standardized incidence rate ratio (IRR) in the radar navy personnel was 0.70 (95% CI: 0.54–0.90). A Cox proportionnal hazard model was performed and no increased risk was found (respectively 0.94 [0.83 – 1.06] and 0.80 [0.01 – 69.15]). In professional militaries no difference in mortality was found according to duration. During a 26-year period of observation. we found no increase in all-cause mortality in french navy personnel who were in close contact with radar equipments.

OBJECTIVE:Non-dissociation of vitamin B12 from its carrying proteins is the most frequent cause of vitamin B12 deficiency in the elderly. The aim of this study was to determine the initial dose of oral cyanocobalamin that would correct the B12 vitamin deficiency within one week.METHODS:This was an open, prospective, study on 30 elderly patients suffering from vitamin deficiency (B12 < 0.20 microg/L) induced by food-cobalamin malabsorption. Ten patients (group I) were treated with a daily dose of 1000 microg of oral cyanocobalamin (from D1 to D8), 10 (group II) with 1000 microg every other day (D1, D3, D5 and D7), 5 (group III) with 1000 microg every 4 days (D1 and D5) and 5 (group IV) with 1000 microg only on D1. The biological response was assessed by control measurement of vitamin B12 serum levels on the 8th day.RESULTS:Mean vitamin B12 serum levels had significantly increased (p < 0.01) in groups I, II and III, but not in group IV. The dose-effect, assessed by the mean increase in vitamin B12 serum levels, was significantly greater (p < 0.05) in groups I (0.25 microg/L) and II (0.18 microg/L), than in groups III and IV (0.09 microg/L).CONCLUSION:This prospective study shows that an oral dose of 1000 microg of cyanocobalamin every 4 days, which corresponds to 250 microg per day, was sufficient to correct B12 vitamin deficiency induced by food-cobalamin malabsorption within one week. However, initial doses of 1000 microg per day or every other day would be preferable because of the greater dose-effect with daily doses higher than 500 microg. A randomised study is warranted to validate these preliminary results.

Objective Non-dissociation of vitamin B12 from its carrying proteins is the most frequent cause of vitamin B12 deficiency in the elderly. The aim of this study was to determine the initial dose of oral cyanocobalamin that would correct the B12 vitamin deficiency within one week. Methods This was an open, prospective, study on 30 elderly patients suffering fro m vitamin deficiency (B12 < 101.20 mu g/L) induced by food-cobalamin malabsorption. Ten patients (group I) were treated with a daily dose of 1000 mu g of oral cyanocobalamin (from D1 to D8), 10 (groupII) with 1000 mu g every other day (D1, D3, D5 and D7), 5 (group III) with 1000 mu g every 4 days (D1 and D5) and 5 (group IV) with 1000 mu g only on D1. The biological response was assessed by control measurement of vitamin B12 serum levels on the 8th day. Results Mean vitamin B12 serum levels had significantly increased (p < 0.01) in groups I, II and III, but not in group IV. The dose-effect, assessed by the mean increase in vitamin B12 serum levels, was significantly greater (p < 0.05) in groups I (0.25 mu g/L) and II (0.18 mu g/L), than in groups III and IV (0.09 mu g/L). Conclusion This prospective study shows that an oral dose of 1000 mu g of cyanocobalamin every 4 days, which corresponds to 250 mu g per day, was sufficient to correct B12 vitamin deficiency induced by food-cobalamin malabsorption within one week. However, initial doses of 1000 mu g per day or every other day would be preferable because of the greater dose-effect with daily doses higher than 500 mu g. A randomised study is warranted to validate these preliminary results.

Introduction Cogan's syndrome is defined by the combination of non syphilitic interstitial keratitis and inner ear dysfunction, similar to Meniere's disease.Observation Cogan's syndrome was revealed by haemorrhagic glaireous diarrhoea in a 21 year-old woman whose medical history included Hirschsprung's disease. Cerebral MRI revealed viral-like bilateral neuritis of the eighth cranial nerve, never described in the literature before. The auditory and visual disorders regressed after treatment with corticosteroids.Conclusion The early diagnosis of Cogan's syndrome permits the cure of the visual and auditory and notably inner ear symptoms with corticosteroid therapy. (c) 2005, Masson, Paris.