The Functional −765G→C Polymorphism of the COX-2 Gene May Reduce the Risk of Developing Crohn's Disease

Contains fulltext : 87827.pdf (publisher's version ) (Open Access)BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1alpha/beta, interferon-gamma and tumor necrosis factor-alpha produced by inflammatory cells. AIM: The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms -1195 A-->G and -765G-->C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population. METHODS: Genomic DNA of 525 patients with Crohn's disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the -1195 A-->G (rs689466) and -765G-->C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated. RESULTS: The genotype distribution of the -1195A-->G polymorphism was not different between the patients with CD or UC and the control group. The -765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04-1.69, pC polymorphism was associated with a reduced risk for developing Crohn's disease in a Dutch population

Syndrome de Parkes-Weber familial

[A familial case of Parkes-Weber syndrome]. Introduction. Parkes-Weber syndrome is usually described as a sporadic form of osteohypertrophic angiodysplasia. However, family forms of Klippel-Trenaunay syndrome have been described. We report the first familial case of Parkes-Weber syndrome. Observation. A boy born at 27 weeks and 6 days of amenorrhea with extensive plane angioma of the right lower limb, right lower part of the back and abdomen. We also noted hypertrophy of this member with venous dilatations. Arterial Doppler ultrasound of the right lower limb showed an aneurysmal varix between the vein and the common femoral artery, confirming a diagnosis of Parkes-Weber syndrome. His maternal first cousin, to years his senior, also presented Parkes-Weber syndrome of the right upper limb. Discussion. This is the first observation of a familial case of Parkes-Weber syndrome in first cousins. Vascular malformations are transmitted in autosomal dominant fashion in the majority of infected families but with incomplete penetrance and variable expressivity. Symptoms appeared to worsen from generation to generation. In each generation of this family, we noted the presence of hemangiomas or capillary malformations with aggravation in the third generation and onset of Parkes-Weber syndrome. Genetic investigation with linkage analysis for the various members in order to identify a predisposing locus yielded little of interest.Introduction: Parmi les angiodysplasies ostéohypertrophiques, le syndrome de Parkes-Weber est habituellement décrit comme sporadique. En revanche, des formes familiales du syndrome de Klippel-Trénaunay ont déjà été rapportées. Nous rapportons la première observation familiale d’un syndrome de Parkes-Weber. Observation : Un garçon, né à 27 semaines et 6 jours d’aménorrhée, était atteint d’un angiome plan étendu du membre inférieur droit, de la partie inférieure droite du dos et de l’abdomen. On notait également une hypertrophie de ce membre et des dilatations veineuses. L’échodoppler artériel du membre inférieur droit mettait en évidence une fistule artérioveineuse entre la veine et l’artère fémorale commune, permettant de poser le diagnostic de syndrome de Parkes-Weber. Sa cousine germaine du côté maternel, son aînée de 10 ans, avait également un syndrome de Parkes-Weber du membre supérieur droit. Discussion : Il s’agit de la première observation d’un cas familial, chez des cousins germains, de syndrome de Parkes-Weber. Les malformations vasculaires se transmettent sur un mode autosomique dominant dans la majorité des familles atteintes avec cependant une pénétrance incomplète et une expressivité variable. Il y aurait une aggravation des symptômes de génération en génération. Chez les membres de cette famille, nous avons constaté dans chaque génération la présence d’hémangiomes ou de malformations capillaires avec une aggravation à la troisième génération devant l’apparition du syndrome de Parkes-Weber. Une enquête génétique avec une analyse de liaison génétique pour les différents membres, à la recherche d’un locus prédisposant a été peu contributive

PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study

International audiencePost-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients

Kidney Transplantation After Allogeneic Hematopoietic Cell Transplantation.

International audienceIntroductionHematopoietic stem cell transplantation (HSCT) aims to cure multiple hematologic malignancies, nonmalignant diseases, metabolic disorders, and immune deficiencies. Along with other transplant-related organ toxicities, both acute and chronic kidney disease are common complications of allogeneic HSCT, affecting 10% to 73% and 0% to 60% of patients respectively, depending on the definitions of kidney dysfunction, duration of follow-up and transplant strategies.S1–S4 The proportion of patients with chronic kidney disease who develop end-stage renal disease is approximately 4%. Among those patients who progress to end-stage renal disease and require hemodialysis, mortality is approximately 90%. Few studies have reported successful kidney transplantation (KT) after HSCT in adults; these were mostly small single-center cohorts often with the same donor for HSCT and kidney, and short follow-up.1,2To investigate mortality and the occurrence of severe infections and cancers, we conducted a French multicenter retrospective study of patients who underwent KT, after previous allogeneic HSCT. The details of study methods are shown in the Supplementary Methods.ResultsNineteen KT patients with a history of HSCT were identified, of whom 3 had received a kidney from the HSCT donor: the remaining 16 patients were included in the analysis (Table 1 and Supplementary Table S1). Patients were allografted between 1986 and 2006, including 12 patients before 2000, at a median age of 31 (9–55) years (3 pediatric patients and 1 patient older than 45 years). The main indication for HSCT was acute leukemia (n = 11/16: 8 acute myeloid leukemia and 3 acute lymphoblastic leukemia). Three patients had undergone 2 consecutive HSCT (2 relapses and 1 autologous HSCT before allogeneic HSCT). Myeloablative conditioning (n = 14/16) was performed and the graft came from a matched related donor (n = 12/16) in the majority of cases. Baseline nephrologic status was partially or fully available for 9 patients. At the time of HSCT, the 2 most recently allografted patients, the only ones to receive nonmyeloablative conditioning regimen, were already on hemodialysis. Two patients were with stage 2 chronic kidney disease and 5 had no kidney failure