Dual factor pulse pressure: body mass index and outcome in type 2 diabetic subjects on maintenance  hemodialysis. A longitudinal study 2003–2006

Lydia Foucan1,2, Kheira Hue3, Jocelyn Inamo1, Jacqueline Deloumeaux1,2, Anne Blanchet-Deverly, et al1Research group Clinical Epidemiology and Medicine of the University of Antilles and Guyane, French West Indies; 2Department of Medical Information and Public Health; 3Nephrology and hemodialysis Unit; 4Cardiology Unit, CHU of Pointe-à-Pitre, Guadeloupe, French West Indies; 5Hemodialysis Unit, Clinic of Choisy Sainte Anne, Guadeloupe, French West IndiesBackground: Inverse associations between risk factors and mortality have been reported in epidemiological studies of patients on maintenance hemodialysis (MHD).Objective: The aim of this prospective study was to estimate the effect of the dual variable pulse pressure (PP) – body mass index (BMI) on cardiovascular (CV) events and death in type 2 diabetic (T2D) subjects on MHD in a Caribbean population.Methods: Eighty Afro-Caribbean T2D patients on MHD were studied prospectively from 2003 to 2006. Proportional-hazard modeling was used.Results: Of all, 23.8% had a high PP (PP ≥ 75th percentile), 76.3% had BMI < 30 Kg/m2, 21.3% had the dual factor high PP – absence of obesity. During the study period, 23 patients died and 13 CV events occurred. In the presence of the dual variable and after adjustment for age, gender, duration of MHD, and pre-existing CV complications, the adjusted hazard ratio (HR) (95% CI) of CV events and death were respectively 2.7 (0.8–8.3); P = 0.09 and 2.4 (1.1–5.9); P = 0.04.Conclusions: The dual factor, high PP – absence of obesity, is a prognosis factor of outcome. In type 2 diabetics on MHD, a specific management strategy should be proposed in nonobese subjects with wide pulse pressure in order to decrease or prevent the incidence of fatal and nonfatal events.Keywords: dual factor, pulse pressure, body mass index, type 2 diabetes, outcom

Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

International audienceSevere combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation