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Le Touquet – Paris-Plage, France

Cordonnier C.,Assistance Publique Hopitaux de Paris AP HP | Labopin M.,University Paris Est Creteil | Chesnel V.,University Paris Est Creteil | Ribaud P.,University Paris Diderot | And 11 more authors.
Vaccine | Year: 2010

The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (≥0.15 μg/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant. © 2010 Elsevier Ltd. All rights reserved.

Busiah K.,University of Paris Descartes | Drunat S.,Robert Debre Teaching Hospital | Vaivre-Douret L.,University Paris - Sud | Bonnefond A.,French National Center for Scientific Research | And 32 more authors.
The Lancet Diabetes and Endocrinology | Year: 2013

Background: Neonatal diabetes mellitus is a rare genetic form of pancreatic β-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without β-cell autoimmunity and with normal pancreas morphology. Methods: We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010. Patients with hyperglycaemia requiring treatment with insulin before age 1 year were eligible, provided that they had normal pancreatic morphology as assessed by ultrasonography and negative tests for β-cell autoimmunity. We assessed changes in the 6q24 locus, KATP-channel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations between genotype and phenotype, with special attention to extra-pancreatic abnormalities. Findings: We tested 174 index patients, of whom 47 (27%) had no detectable genetic defect. Of the remaining 127 index patients, 40 (31%) had 6q24 abnormalities, 43 (34%) had mutations in KCNJ11, 31 (24%) had mutations in ABCC8, and 13 (10%) had mutations in INS. We reported developmental delay with or without epilepsy in 13 index patients (18% of participants with mutations in genes encoding KATP channel subunits). In-depth neuropsychomotor investigations were done at median age 7 years (IQR 1-15) in 27 index patients with mutations in KATP channel subunit genes who did not have developmental delay or epilepsy. Developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits were recorded in all index patients who had this testing. Compared with index patients who had mutations in KATP channel subunit genes, those with 6q24 abnormalities had specific features: developmental defects involving the heart, kidneys, or urinary tract (8/36 [22%] vs 2/71 [3%]; p=0·002), intrauterine growth restriction (34/37 [92%] vs 34/70 [48%]; p<0·0001), and early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p<0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36). Interpretation: Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus. Funding: Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie. © 2013 Elsevier Ltd.

Bismuth E.,Robert Debre Teaching Hospital | Chevenne D.,Robert Debre Teaching Hospital | Czernichow P.,Robert Debre Teaching Hospital | Simon D.,Robert Debre Teaching Hospital
Hormone Research in Paediatrics | Year: 2010

Objectives: To describe glucose metabolism changes during growth hormone (GH) treatment in juvenile idiopathic arthritis (JIA). Study Design: Observational study in 58 children on glucocorticoid therapy (GC) for JIA, of whom 28 received late GH therapy (7.3 ± 3.4 years into GC), 15 early GH therapy (1.2 ± 0.1 years into GC), and 15 no GH therapy. The GH dose was 0.46 mg/kg/week. Oral glucose tolerance testing with insulin and glycosylated hemoglobin assays were performed yearly. Nonparametric tests were used to compare groups after 3 years and regression analyses to estimate factors predicting glucose AUC and HOMA-IR at baseline and after 3 years. Results: GH combined with GC was associated with an increase in mean fasting insulinemia. Late GH therapy patients exhibited significant increases over time in mean fasting glycemia (p = 0.01), mean 2-hour postglucose load glycemia (p < 0.05), mean AUC for glucose (p < 0.05), and mean HOMA-IR (p < 0.05). Impaired glucose tolerance was found in 16/43 GH-treated patients (37%) and transient diabetes in 2 (5%) patients. Conclusions: GH treatment in JIA children decreased insulin sensitivity but had only modest effects on glucose tolerance. Close monitoring by oral glucose tolerance testing is crucial before and during GH treatment, particularly during puberty and relapses. Copyright © 2010 S. Karger AG, Basel.

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