| 1. |
- Lundell, M, et al.
(författare)
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Low incidence of brain death and organ donation in Sweden. Analyses of a six-year prospective registration of all deceased patients in intensive units in Southern Sweden
- 2006
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Ingår i: Organs, Tissues and Cells. - 1828-0595. ; 9:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Sweden is among those countries in Europe that have the lowest number of organ donors per million population (PMP). Because of the low numbers of actual donors, it is important to identify the total number of potential donors. Thus, a prospective registration of all deceased patients at all intensive care units was introduced in the Southern Healthcare Region of Sweden, which has a population of 1.6 million. During the six years from 1999 to 2004, 3,760 deaths were recorded. Only 251 patients (7%) of all ages were diagnosed with brain death, corresponding to 26 patients PMP and year. Of these, 194 cases (20 PMP) were classified as potential organ donors, defined as brain death without medical contraindications against organ donation. Consent for organ donation was given in slightly more than half of these cases (54%) thus, there were only around 11 organ donors PMP and year. The continuous registration in Southern Sweden has been a very important tool for evaluation of what forms of action should be taken to promote organ donation. As part of a computerised system for quality assurance in intensive care now being introduced in many parts of Sweden, registration may become an instrument of quality assurance for organ donation nationwide.
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| 2. |
- Ohlsson, Björn, et al.
(författare)
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Follow-up after curative surgery for colorectal carcinoma - Randomized comparison with no follow-up
- 1995
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706. ; 38:6, s. 619-626
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study investigated the value of intense follow-up compared with no follow-up after curative surgery of cancer in the colon or rectum. METHODS: One hundred seven patients were randomized to no follow-up (control group; n=54) or intense follow-up (follow-up group; n=53) after surgery and early postoperative colonoscopy. Patients in the follow-up group were followed at frequent intervals with clinical examination, rigid proctosigmoidoscopy, colonoscopy, computed tomography of the pelvis (in patients operated with abdominoperineal resection), pulmonary x-ray, liver function tests, and determinations of carcinoembryonic antigen and fecal hemoglobin. Follow-up ranged from 5.5 to 8.8 years after primary surgery. RESULTS: Tumor recurred in 18 patients (33 percent) in the control group and in 17 patients (32 percent) in the follow-up group. Reresection with curative intent was performed in three patients in the control group and in five patients (four of whom were asymptomatic) in the follow-up group. In the follow-up group two asymptomatic patients with elevated carcinoembryonic antigen levels were disease-free three and five and one-half years after reresection and were the only patients apparently cured by reresection. No patient underwent surgery for metastatic disease in the liver or lungs. Symptomatic metachronous carcinoma was detected in one patient (control group) after three years. Five-year survival rate was 67 percent in the control group and 75 percent in the follow-up group (P >0.05); the corresponding cancer-specific survival rates were 71 percent and 78 percent, respectively. CONCLUSION: Intense follow-up after resection of colorectal cancer did not prolong survival in this study.
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| 3. |
- Bouamar, R., et al.
(författare)
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Tacrolimus Predose Concentrations Do Not Predict the Risk of Acute Rejection After Renal Transplantation: A Pooled Analysis From Three Randomized-Controlled Clinical Trials
- 2013
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 13:5, s. 1253-1261
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic drug monitoring (TDM) for tacrolimus (Tac) is universally applied. However, the concentrationeffect relationship for Tac is poorly defined. This study investigated whether Tac concentrations are associated with acute rejection in kidney transplant recipients. Data from three large trials were pooled. We used univariate and multivariate analysis to investigate the relationship between biopsy-proven acute rejection (BPAR) and Tac predose concentration at five time points (day 3, 10 and 14, and month 1 and 6 after transplantation). A total of 136/1304 patients experienced BPAR, giving an overall incidence of 10.4%. We did not find any significant correlations between Tac predose concentrations and the incidence of BPAR at the different time points. In the multivariate analysis, only delayed graft function (DGF) and the use of induction therapy were independently correlated with BPAR, with an odds ratio of 2.7 [95% CI: 1.84.0; p < 0.001] for DGF and 0.66 [95% CI: 0.440.99; p = 0.049] for induction therapy. The other variables, including the Tac predose concentrations, were not statistically significantly associated with BPAR. We did not find an association between the Tac predose concentrations measured at five time points after kidney transplantation and the incidence of acute rejection occurring thereafter. Based on this study it is not possible to define the optimal target concentrations for Tac.
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| 4. |
- Cantarovich, M, et al.
(författare)
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First global forum on education on organ donation and transplantation for schools.
- 2012
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Ingår i: Pediatric Transplantation. - : Wiley. - 1399-3046 .- 1397-3142.
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Tidskriftsartikel (refereegranskat)abstract
- The Transplantation Society, in collaboration with the Canadian Society of Transplantation, organized a forum on education on ODT for schools. The forum included participants from around the world, school boards, and representatives from different religions. Participants presented on their countries' experience in the area of education on ODT. Working groups discussed about technologies for education, principles for sharing of resources globally, and relationships between education, and health authorities and non-governmental organizations. The forum concluded with a discussion about how to best help existing programs and those wishing to start educational programs on ODT.
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| 5. |
- Corbascio, Matthias, et al.
(författare)
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Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice.
- 2002
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Ingår i: Transplantation. - 1534-6080. ; 74:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions, cytotoxicity assays, skin transplantation, and vascularized heterotopic heart transplantation in wild-type B6 and CD40L-deficient mice in the presence and absence of anti-LFA-1 to study the effects of anti-LFA-1 in the absence of CD40L signaling. RESULTS: Anti-LFA-1 inhibited proliferation of naïve CD40L-/- mixed leukocyte reactions and the lysis of donor targets by CD40L-/- cytotoxic T lymphocytes. Anti-LFA-1-treated CD40L-/- mice that received fully MHC-mismatched skin grafts showed significant prolongation of graft survival, with a median survival time of 55 days (mean 66 days) compared with 13 and 21 days in wild-type and CD40L-/- controls, respectively. CD40L-/- mice that received fully MHC-mismatched vascularized heart transplants treated with four doses of 200 microg of anti-LFA-1 at the time of transplantation did not develop any signs of chronic vasculopathy 150 days after transplantation. CONCLUSION: These results indicate that anti-LFA-1 can complement CD40L inhibition in the prevention of undesirable immune responses.
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| 6. |
- Demirbas, Alper, et al.
(författare)
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Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:12, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- P>Regional transplant practices may affect clinical outcomes within multinational studies. This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries. De novo adult renal transplant recipients (n = 1645) were randomized to receive standard-dose cyclosporine, or daclizumab induction plus low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus, all in addition to mycophenolate mofetil and steroids. Data for the highest patient-recruiting countries, Spain (n = 275), Germany (n = 316) and Turkey (n = 258), were compared. Patient transplant characteristics were different among the country subsets; only deceased donors in Spain, more expanded criteria donors in Germany, and mainly living donors in Turkey. Efficacy results for the three countries were consistent with that of the overall study - renal function and biopsy-proven acute rejection (BPAR) rates were superior with low-dose tacrolimus. Turkey had higher mean calculated glomerular filtration rate across all treatment groups (60.6-72.2 ml/min) compared with that of Spain (51.1-57.5 ml/min) and Germany (51.3-62.9 ml/min). Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study; Germany had much higher rates (21.0-54.2%). These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in randomized clinical trials.
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| 7. |
- Diab, R, et al.
(författare)
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Effect of triple costimulation blockade on islet allograft survival in sensitized mice.
- 2010
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 1873-2623 .- 0041-1345. ; 42:6, s. 2109-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Islet allograft rejection in sensitized recipients is difficult to control by costimulation blockade using anti-CD154 and cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4Ig). Because leukocyte function antigen (LFA) 1 is highly expressed on memory T cells, adding an LFA-1 blockade may inhibit memory T-cell activities. We examined the effects on islet allograft survival of triple costimulation blockade in presensitized recipient mice. METHODS: C57BL/6 mice were sensitized by transplantation under the kidney capsule or intraperitoneal injection of Balb/c islets. Four weeks after transplantation, sensitization was confirmed by flow-cytometric detection of alloreactive antibodies. Diabetes was induced by a single intravenous injection of streptozotocin. Recipients were transplanted with 200 Balb/c islets under the right kidney capsule. Graft function was assessed by daily blood glucose and body weight records. Transplanted animals were divided into 3 treatment groups: group 1, control antibody; group 2, anti-CD154 and CTLA-4 Ig double therapy; group 3, anti-CD154, CTLA4Ig, and anti-LFA-1 triple therapy. Injections were administered every second day from day -2 to day 8. RESULTS: Naïve mice rejected islet allografts between days 7 and 29 (mean 16 +/- 6 d; n = 5), sensitized mice in group 1 between days 0 and 14 (mean 7 +/- 5 d; n = 8), in group 2 between days 4 and 16 (mean 8 +/- 4 d; n = 7), and in group 3 between days 4 and 26 (mean 11 +/- 7 d; n = 10). CONCLUSION: Triple costimulation blockade with anti-CD154, CTLA4Ig, and anti-LFA-1 was not sufficient to improve islet allograft survival in sensitized recipients.
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| 8. |
- Ekberg, Henrik, et al.
(författare)
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Calcineurin Inhibitor Minimization in the Symphony Study: Observational Results 3 Years after Transplantation.
- 2009
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 9, s. 1876-1885
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Tidskriftsartikel (refereegranskat)abstract
- The Symphony study showed that at 1 year posttransplant, a regimen based on daclizumab induction, 2 g mycophenolate mofetil (MMF), low-dose tacrolimus and steroids resulted in better renal function and lower acute rejection and graft loss rates compared with three other regimens: two with low-doses of cyclosporine or sirolimus instead of tacrolimus and one with no induction and standard cyclosporine dosage. This is an observational follow-up for 2 additional years with the same endpoints as the core study. Overall, 958 patients participated in the follow-up. During the study, many patients changed their immunosuppressive regimen (e.g. switched from sirolimus to tacrolimus), but the vast majority (95%) remained on MMF. During the follow-up, renal function remained stable (mean change: -0.6 ml/min), and rates of death, graft loss and acute rejection were low (all about 1% per year). The MMF and low-dose tacrolimus arm continued to have the highest GFR (68.6 +/- 23.8 ml/min vs. 65.9 +/- 26.2 ml/min in the standard-dose cyclosporine, 64.0 +/- 23.1 ml/min in the low-dose cyclosporine and 65.3 +/- 26.2 ml/min in the low-dose sirolimus arm), but the difference with the other arms was not significant (p = 0.17 in an overall test and 0.077, 0.039 and 0.11, respectively, in pair-wise tests). The MMF and low-dose tacrolimus arm also had the highest graft survival rate, but with reduced differences between groups over time, and the least acute rejection rate. In the Symphony study, the largest ever prospective study in de novo kidney transplantation, over 3 years, daclizumab induction, MMF, steroids and low-dose tacrolimus proved highly efficacious, without the negative effects on renal function commonly reported for standard CNI regimens.
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| 9. |
- Ekberg, Henrik
(författare)
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Calcineurin inhibitor sparing in renal transplantation
- 2008
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Ingår i: Transplantation. - 1534-6080. ; 86:6, s. 761-767
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Forskningsöversikt (refereegranskat)abstract
- Although calcineurin inhibitors (CNIs) are effective at preventing a cute rejection, their long-term use is associated with nephrotoxicity that may compromise long-term renal allograft Survival. Consequently, there is considerable interest in identifying immunosuppressive regimens that permit reduced exposure to CNIs while maintaining adequate immunosuppression. Introducing such strategies early after transplantation may mean that the development of CNI-associated nephrotoxicity could be minimized or prevented. Several CNI-sparing regimens have shown at least comparable efficacy with standard-dos CNI regimens. In particular, a regimen of mycophenolate mofetil (MMF), corticosteroids, interleukin-2 receptor antagonist induction, and low-dose tacrolimus from the time of transplantation provided superior renal function and a lower acute rejection rate than the same regimen but with low-dose cyclosporine or low-close sirolimus, or standard-dose cyclosporine, MMF, and corticosteroids. The use of low-dose cyclosporine does not seem to eliminate nephrotoxicity in de novo renal transplant recipients. The early withdrawal of CNIs from MMF-based regimens generally improves renal function but has been associated with an increased risk of acute rejection, in particular when the levels of mycophenolic acid were not adjusted to maintain the same total level Of immunosuppression. Research aiming to achieve the "best" balance of efficacy and toxicity of available immunosuppressive regimens continues.
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| 10. |
- Ekberg, Henrik, et al.
(författare)
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Challenges and considerations in diagnosing the kidney disease in deteriorating graft function.
- 2012
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Ingår i: Transplant international : official journal of the European Society for Organ Transplantation. - : Frontiers Media SA. - 1432-2277. ; 25:11, s. 1119-1128
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Tidskriftsartikel (refereegranskat)abstract
- Despite significant reductions in acute-rejection rates with the introduction of calcineurin inhibitor (CNI)-based immunosuppressive therapy, improvements in long-term graft survival in renal transplantation have been mixed. Improving long-term graft survival continues to present a major challenge in the management of kidney-transplant patients. CNIs are a key component of immunosuppressive therapy, and chronic CNI toxicity has been widely thought to be a major factor in late graft failure. However, recent studies examining the causes of late graft failure in detail have challenged this view, highlighting the importance of antibody-mediated rejection and other factors. In addition, the diagnosis of CNI nephrotoxicity represents a challenge to clinicians, with the potential for over-diagnosis and an inappropriate reduction in immunosuppressive therapy. When graft function is deteriorating, accurately determining the cause of the kidney disease is essential for effective long-term management of the patient. Diagnosis requires a thorough clinical investigation, and in the majority of cases a specific cause can be identified.
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