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Le Touquet – Paris-Plage, France

Lebranchu Y.,University of Tours | Snanoudj R.,Necker Enfants Malades University Hospital | Toupance O.,University Hospital | Weestel P.-F.,University Hospital | And 11 more authors.
American Journal of Transplantation

Calcineurin inhibitors improve acute rejection rates and short-term graft survival in renal transplantation, but their continuous use may be deleterious. We evaluated the 5-year outcomes of sirolimus (SRL) versus cyclosporine (CsA) immunosuppressive treatment. This observational study was an extension of the SPIESSER study where deceased donor kidney transplant recipients were randomized before transplantation to a SRL- or CsA-based regimen and followed up 1 year. Data from 131 (63 SRL, 68 CsA) out of 133 patients living with a functional graft at 1 year were collected retrospectively at 5 years posttransplant. Seventy percent of CsA patients versus 54% of SRL patients were still on the allocated treatment at 5 years (p = 0.091), most discontinuations in each group being due to safety issues. In intent-to-treat, mean MDRD eGFR was higher with SRL: 54.2 versus 45.3 mL/min with CsA (p = 0.019); SRL advantage was greater in on-treatment analyses. Therewere no differences for patient survival (p=0.873), graft survival (p=0.121) and acute rejection (p = 0.284). Adverse events were more frequent with SRL (80% vs. 60%, p = 0.015). Results confirmed the high SRL discontinuation rate due to adverse events. Nevertheless, a benefit was evidenced on renal function in patients (more than 50%) still on treatment at 5 years. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons. Source

Brousse V.,University Hospital Necker Enfants Malades | Brousse V.,French Institute of Health and Medical Research | Brousse V.,Laboratory of Excellence | Brousse V.,University of Paris Descartes | And 4 more authors.
British Journal of Haematology

Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in children are infarctive stroke, transient ischaemic attack and cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and recurrent headache are also common. Cerebrovascular disease selectively affects children with the HbSS or HbS-β0 genotypes (i.e. sickle cell anaemia). The incidence of stroke peaks between 2 and 5 years of age (1·02/100 patient-years) and increases with the severity of the anaemia. Most strokes can be prevented by annual transcranial Doppler screening from 2 to 16 years of age and providing chronic blood transfusion when this investigation shows elevated blood-flow velocities. The role for hydroxycarbamide in children with abnormal transcranial Doppler findings is under investigation. After a stroke, chronic blood transfusion is very strongly recommended, unless haematopoietic stem cell transplantation can be performed. Routine magnetic resonance imaging shows that more than one-third of children have silent cerebral infarction, which is associated with cognitive impairments. Screening for silent infarcts seems legitimate, since their presence may lead to supportive treatments. The role for more aggressive interventions such as hydroxycarbamide or chronic blood transfusion is debated. © 2015 John Wiley & Sons Ltd. Source

Souberbielle J.-C.,Necker Enfants Malades University Hospital | Cavalier E.,University of Liege | Cormier C.,Cochin University Hospital
Annales d'Endocrinologie

The aim of this article is to discuss the diagnostic approach of an increased serum PTH concentration in a normocalcemic, normophosphatemic patient. Detection of this biological presentation is frequent in routine practice all the more that PTH reference values established in vitamin D replete subjects with a normal renal function are used by the clinical laboratories. The first step in this diagnostic approach will be to rule out a cause of secondary hyperparathyroidism (SHPT). Among these, the most frequent are vitamin D deficiency, very low calcium intake, impaired renal function, malabsorptions, drugs interfering with calcium/bone metabolism, such as lithium salts and antiresorptive osteoporosis therapies, hypercalciuria due to a renal calcium leak. If no cause of SHPT are evidenced, the diagnosis of normocalcemic primary hyperparathyroidism (PHPT) should be considered. A calcium load test is a very useful tool for this diagnosis if it shows that serum PTH is not sufficiently decreased when calcemia rises frankly above the upper normal limit. In a normocalcemic patient with hypercalciuria and a high serum PTH concentration, a thiazide challenge test may help to differentiate SHPT due to a renal calcium leak from normocalcemic PHPT. Beyond the discussion of this diagnostic flowchart, we also discuss some points about the merits and the difficulties of measuring and interpreting ionized calcemia and 24-h calciuria. © 2015 Elsevier Masson SAS. Source

Haase J.K.,University College Cork | Didelot X.,Imperial College London | Lecuit M.,French Institute of Health and Medical Research | Lecuit M.,Necker Enfants Malades University Hospital | And 7 more authors.
Environmental Microbiology

Listeria monocytogenes is ubiquitously prevalent in natural environments and is transmitted via the food chain to animals and humans, in whom it can cause life-threatening diseases. We used Multilocus Sequence Typing (MLST) of ~2000 isolates of L.monocytogenes to investigate whether specific associations existed between clonal complexes (CCs) and the environment versus diseased hosts. Most CCs (72%) were not specific for any single source, and many have been isolated from the environment, food products, animals as well as from humans. Our results confirm that the population structure of L.monocytogenes is largely clonal and consists of four lineages (I-IV), three of which contain multiple CCs. Most CCs have remained stable for decades, but one epidemic clone (CC101) was common in the mid-1950s and very rare until recently when it may have begun to re-emerge. The historical perspective used here indicates that the central sequence types of CCs were not ancestral founders but have rather simply increased in frequency over decades. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd. Source

Chenal-Francisque V.,Institute Pasteur Paris | Chenal-Francisque V.,French Institute of Health and Medical Research | Diancourt L.,Institute Pasteur Paris | Cantinelli T.,Institute Pasteur Paris | And 14 more authors.
Journal of Clinical Microbiology

Populations of the food-borne pathogen Listeria monocytogenes are genetically structured into a small number of major clonal groups, some of which have been implicated in multiple outbreaks. The goal of this study was to develop and evaluate an optimized multilocus variable number of tandem repeat (VNTR) analysis (MLVA) subtyping scheme for strain discrimination and clonal group identification. We evaluated 18 VNTR loci and combined the 11 best ones into two multiplexed PCR assays (MLVA-11). A collection of 255 isolates representing the diversity of clonal groups within phylogenetic lineages I and II, including representatives of epidemic clones, were analyzed by MLVA-11, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). MLVA-11 had less discriminatory power than PFGE, except for some clones, and was unable to distinguish some epidemiologically unrelated isolates. Yet it distinguished all major MLST clones and therefore constitutes a rapid method to identify epidemiologically relevant clonal groups. Given its high reproducibility and high throughput, MLVA represents a very attractive first-line screening method to alleviate the PFGE workload in outbreak investigations and listeriosis surveillance. Copyright © 2013, American Society for Microbiology. All Rights Reserved. Source

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