Robert Debre Teaching Hospital
Robert Debre Teaching Hospital
Cordonnier C.,Henri Mondor Teaching Hospital |
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.
Jayol A.,University Paris Diderot |
Janvier F.,University Paris Diderot |
Janvier F.,Military Hospital Sainte Anne |
Guillard T.,University Paris Diderot |
And 8 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016
Objectives: To determine the genetic location and environment of the qnrA6 gene in Proteus mirabilis PS16 where it was first described and to characterize the quinolone resistance qnrA6 confers. Methods: Transformation experiments and Southern blotting were performed for plasmid and genomic DNA of P. mirabilis PS16 to determine the qnrA6 location. Combinatorial PCRs with primers in qnrA6 and genes usually surrounding qnrA genes were used to determine the genetic environment. The qnrA6 coding region, including or not the promoter region, was cloned into vectors pTOPO and pBR322 and the MICs of six quinolones were measured for transformants of Escherichia coli TOP10 and P. mirabilis ATCC 29906 RifR. Results: QnrA6 was shown to be chromosomally encoded in P. mirabilis PS16 and its genetic environment was 81%-87% similar to that of qnrA2 in the Shewanella algae chromosome. The 5138 bp region up- and downstream of qnrA6 contained an IS10 sequence surrounded by two ISCR1. This resulted in qnrA6 being displaced 1.9 kb from its native promoter but supplied a promoter present in ISCR1. qnrA6 cloned into pTOPO and pBR322 conferred a 4-32-fold increase in fluoroquinolone MICs when expressed in E. coli but only 2-3-fold in P. mirabilis. When including the promoter region, a further increase in resistance was observed in both species, reaching MIC values above clinical breakpoints for only P. mirabilis. Conclusions: QnrA6 is the first chromosomally located qnrA gene described in Enterobacteriaceae. The quinolone resistance conferred by qnrA6 depends on the proximity of an efficient promoter and the host strain where it is expressed. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
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.
PubMed | Robert Debre Teaching Hospital
Type: Journal Article | Journal: Hormone research in paediatrics | Year: 2010
To describe glucose metabolism changes during growth hormone (GH) treatment in juvenile idiopathic arthritis (JIA).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.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.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.