43 research outputs found

    Psychosocial risk factors for impaired health‑related quality of life in living kidney donors: results from the ELIPSY prospective study

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    Living kidney donors' follow-up is usually focused on the assessment of the surgical and medical outcomes. Whilst the psychosocial follow-up is advocated in literature. It is still not entirely clear which exact psychosocial factors are related to a poor psychosocial outcome of donors. The aim of our study is to prospectively assess the donors' psychosocial risks factors to impaired health-related quality of life at 1-year post-donation and link their psychosocial profile before donation with their respective outcomes. The influence of the recipient's medical outcomes on their donor's psychosocial outcome was also examined. Sixty donors completed a battery of standardized psychometric instruments (quality of life, mental health, coping strategies, personality, socio-economic status), and ad hoc items regarding the donation process (e.g., motivations for donation, decision-making, risk assessment, and donor-recipient relationship). Donors' 1-year psychosocial follow-up was favorable and comparable with the general population. So far, cluster-analysis identified a subgroup of donors (28%) with a post-donation reduction of their health-related quality of life. This subgroup expressed comparatively to the rest, the need for more pre-donation information regarding surgery risks, and elevated fear of losing the recipient and commitment to stop their suffering

    Thiopurine Methyltransferase Predicts the Extent of Cytotoxicty and DNA Damage in Astroglial Cells after Thioguanine Exposure

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    Thiopurine methyltransferase (Tpmt) is the primary enzyme responsible for deactivating thiopurine drugs. Thiopurine drugs (i.e., thioguanine [TG], mercaptopurine, azathioprine) are commonly used for the treatment of cancer, organ transplant, and autoimmune disorders. Chronic thiopurine therapy has been linked to the development of brain cancer (most commonly astrocytomas), and Tpmt status has been associated with this risk. Therefore, we investigated whether the level of Tpmt protein activity could predict TG-associated cytotoxicity and DNA damage in astrocytic cells. We found that TG induced cytotoxicity in a dose-dependent manner in Tpmt+/+, Tpmt+/− and Tpmt−/− primary mouse astrocytes and that a low Tpmt phenotype predicted significantly higher sensitivity to TG than did a high Tpmt phenotype. We also found that TG exposure induced significantly more DNA damage in the form of single strand breaks (SSBs) and double strand breaks (DSBs) in primary astrocytes with low Tpmt versus high Tpmt. More interestingly, we found that Tpmt+/− astrocytes had the highest degree of cytotoxicity and genotoxicity (i.e., IC50, SSBs and DSBs) after TG exposure. We then used human glioma cell lines as model astroglial cells to represent high (T98) and low (A172) Tpmt expressers and found that A172 had the highest degree of cytoxicity and SSBs after TG exposure. When we over-expressed Tpmt in the A172 cell line, we found that TG IC50 was significantly higher and SSB's were significantly lower as compared to mock transfected cells. This study shows that low Tpmt can lead to greater sensitivity to thiopurine therapy in astroglial cells. When Tpmt deactivation at the germ-line is considered, this study also suggests that heterozygosity may be subject to the greatest genotoxic effects of thiopurine therapy

    [Treatment With Lo-tact-1, a Monoclonal-antibody To the Interleukin-2 Receptor, in Renal-transplantation]

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    From May to August 1989 15 cadaver-donor renal transplant recipients were treated for 14 days with LO-Tact-1 (10 mg i.v. per day) in combination with cyclosporin (8 mg/kg/day from day -1), low-dose steroids (1/2 mg/kg/day from day 1, then reduced to 0.25 mg/kg at day 26 and 10 mg/day at day 45), and azathioprine (1 mg/kg/day) started at day 45. LO-Tact-1 is a rat monoclonal antibody which is directed to the interleukin-2 receptor. The control group consisted of 20 patients receiving cyclosporin, high-dose steroids (2 mg/day at day 1) and a 14-day course of polyclonal horse antilymphocyte globulins (ALG). Seven patients experienced 9 rejections during the first 3 months post-transplant between day 10 and day 67 (mean 0.6 per patient), comparable to the incidence of rejections in the control group: 8 rejections in 7 patients (mean 0.4 per patient). All rejections were reversed by steroid boluses and ATG. To date, all study patients have functioning grafts, and at 1-year post-transplant, the mean blood creatinine level is 161.2-mu-mol/l. In the control group, one patient died of CMV infection, and 2 other grafts failed due to rejection. No adverse effect of antibody administration was observed, and hematological changes remained of minor importance. Viral infections were not observed, except one case of herpes simplex. Comparatively, clinical CMV infections occurred in 3 patients receiving ALG (15 percent). Our data suggest that a combination anti-IL-2 monoclonal antibody, cyclosporin and low-dose steroids can safely be administered to allograft recipients, avoid severe viral infections, and, in our early experience, is as potent as the powerful combination ALG, cyclosporin and high-doses steroids in preventing allograft rejection
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