Increased telomere attrition following renal transplantation: impact of anti-metabolite therapy

Background: The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. Methods: In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls. Results: Non-CKD patients had significantly (P <= 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P = 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P = 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P < 0.0001), whereas the opposite was true for homocysteine (P < 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P = 0.003). Conclusions: The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention

AB0-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab

5As the demand for kidney transplantation is constantly growing methods to expand thedonor pool have become increasingly important. AB0-incompatibility has hitherto been re-garded as an absolute contraindication to living donor donation. However, as AB0-incom-patibility has accounted for the majority of living donor exclusions, efforts have been madeto overcome this immunologic barrier. Successful desensitization protocols thus far, havecombined plasmapheresis for antibody removal with splenectomy to reduce the antibodyproducing B-cell pool, in addition to quadruple immunosuppression. Although good graftfunction has been achieved, the high risks involved have been deterrent. A protocol for AB0-incompatible kidney transplantation based on antigen-specific im-munoadsorption and rituximab, in combination with standard maintenance immunosup-pression (tacrolimus, mycophenolate mofetil and corticosteroids) was developed. We hypo-thesized that the anti-A/B antibodies could be effectively eliminated and good graft func-tion achieved, without the complications of coagulopathy and transfusion reactions associ-ated with plasmapheresis. Furthermore, we hypothesized that the substitution of splenecto-my with a single dose of the B-lymphocyte depleting antibody, rituximab, would abolish thesurgical risk and reduce the risk of infectious complications related to splenectomy. From Sept 2001 to Oct 2007 a total of 39 patients underwent conditioning for AB0-incompatible kidney transplantation according to the protocol. Median follow-up was 2years. In 38 out of 39 patients the anti-A/B antibodies could be effectively removed andtransplantation performed as planned. The antigen-specific immunoadsorption was welltolerated without any serious side effects. Overall patient survival was 97.4% and graftsurvival was 86.8%. Kidney function was evaluated in a short and long term perspective,the results being equivalent to those of AB0-compatible living donor kidney transplanta-tion. The incidence of antibody-mediated rejection was 2.6% and there was no significantrebound of anti-A/B antibodies during the study period. However, AB0-incompatible kid-ney transplantation was associated with an additional cost of approximately 32,000 com-pared with standard AB0-compatible living donor kidney transplantation. B-lymphocytes were effectively eliminated long-term in peripheral blood as well as wit-hin the kidney transplant. In the lymphoid compartment, the B-lymphocytes were reduced.Despite B-lymphocyte depletion, there was no increased risk of infection following AB0-incompatible kidney transplantation compared with AB0-compatible transplantation. We conclude that AB0-incompatible kidney transplantation using a protocol based onantigen-specific immunoadsorption and rituximab, in combination with triple immuno-suppressive therapy is safe and effective. AB0-incompatibility following this protocol doesnot have a negative impact on graft function. AB0-incompatible kidney transplantation usingthis protocol is equivalent to standard AB0-compatible living donor kidney transplantation

Consultants'trust to their reward system : a study in project based firms

Bakgrund: Arbetstagarens kunskap ses som en allt viktigare resurs och företag söker vägar att behålla duktiga kunskapsarbetare. Ett företags belöningssystem kan vara ett sätt för att attrahera och behålla kunskapsarbetare. I studien läggs fokus på konsulter då de är kunskapsarbetare som lever på sin kompetens och oftast arbetar i projekt. För att en kunskapsarbetare ska bli motiverad av den belöning denne får menar vi att det krävs att kunskapsarbetaren känner tillit till belöningssystemet och dess förmåga att uppmärksamma och belöna kunskapsarbetarens arbetsinsats. Syfte: Syftet med denna uppsats är att analysera faktorer som påverkar kunskapsarbetares tillit till belöningssystem i en projektbaserad organisation. Genomförande: Intervjuer har genomförts med sex konsulter och två chefer på två större konsultbolag; tre konsulter och en chef på varje företag. Resultat: Studien visar att de belöningssystem som används i de undersökta företagen generellt är uppskattade av konsulterna i respektive företag och de känner tillit till att de får den belöning de anser sig förtjäna. Konsulterna framhåller specifika faktorer som viktiga för att de ska känna tillit till belöningssystemet. De faktorer som har visat sig vara av betydelse är rättvisa, pålitlighet, öppenhet och kompetens

Luft & miljö 2017 Barns hälsa

Barn ar sarskilt utsatta for luftfororeningar, dels genom sin fysik, men aven genom sina dagliga rorelsemonster. Manga barn vaxer idag upp i miljoer dar dalig luftkvalitet kan paverka deras framtida halsa. For att vi ska kunna skapa en luftmiljo som ar bra for barns halsoutveckling, behover vi tanka pa hur vi utformar stader och narmiljo och vi behover kunskap om hur barn paverkas av den luftkvalitet som omger dem. Idag behover vi aven ta hansyn till de konsekvenser som klimatforandringarna for med sig och som paverkar barns fysiska och psykiska halsa. Overvakning av luftkvalitet ar viktig i bade tatorten och pa landsbygden for att vi ska kunna folja hur halterna av luftfororeningar utvecklas, bade over tid och hur de varierar i olika miljoer. Forskare kombinerar uppgifter om barns halsa med luftkvalitetsdata vid relevanta platser och kan pa sa vis se vilken paverkan luftfororeningarna har. Den har skriften har tagits fram inom ramen for Naturvardsverkets arbete med nationell miljoovervakning, och ar fylld med innehall dels av dem som utfor overvakningen, men aven av forskare vid universitet och hogskolor, myndigheter och andra aktorer. Skriften ar tankt att vara ett inspirationsdokument for handlaggare pa kommuner och lansstyrelser som arbetar med miljo- och planeringsfragor med koppling till barn och deras halsa samt for politiker. Med ett barnperspektiv vid planering och beslut hoppas vi att samhallet banar vagen for en framtid med battre luft for alla. Lat er inspireras och verka for en battre luftmiljo for barn

A Randomized, Doubleblind, Placebo-Controlled, Study of Single-Dose Rituximab as Induction in Renal Transplantation

We performed a prospective, double blind, randomized, placebo-controlled multicenter study on the efficacy and safety of rituximab as induction therapy, together with tacrolimus, mycophenolate mofetil, and steroids. The primary endpoint was defined as acute rejection, graft loss, or death during the first 6 months. Secondary endpoints were creatinine clearance, incidence of infections, and incidence of rituximab-related adverse event. Results. We enrolled 140 patients (44 living donor and 96 deceased donor), and of those, 68 rituximab and 68 placebo patients fulfilled the study. In all the patients receiving rituximab, there was a complete depiction of CD 19/CD20 cells, whereas there was no change in the number of CD19/CD20 cells in the placebo group. There were 10 treatment failures in the rituximab group versus 14 in the placebo group (P=0.348). There were eight rejection episodes in the rituximab group versus 12 in the placebo group (P=0.317) Creatinine clearance was 66 +/- 22 mL/min in the study group and 67 +/- 23 mL/min in the placebo group. There was no difference in the number of bacterial infections, cytomegalovirus infections, and BK virus infections or fungal infections. Conclusion. We performed a placebo-controlled study of rituximab induction in renal transplantation. There was a tendency toward fewer and milder rejections during the first 6 months in the rituximab group. Although induction with one dose of rituximab induced a complete depletion B cells, there was no increase in the incidence of infectious complications or leukopenia and it seems safe, therefore, to conduct further studies on the use of rituximab in transplantation