| 1. |
- Lundell, M, et al.
(author)
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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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In: Organs, Tissues and Cells. - 1828-0595. ; 9:1, s. 23-27
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Journal article (peer-reviewed)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. |
- Persson, Nils, et al.
(author)
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Sverige har potential för organdonation. Analys av fem års heltäckande registrering av IVA-dödsfall i södra Sverige
- 2005
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In: Läkartidningen. - 0023-7205. ; 102:9, s. 638-641
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Journal article (peer-reviewed)abstract
- A complete registration of all deceased patients at intensive care units in the Southern Health region of Sweden has shown that 3,114 patients died during the five years from 1999 to 2003. Only 174 cases (5.6 per cent) were classified as potential organ donors according to the definition of total brain infarction (brain death) without medical contra-indications against organ donation. Consent for organ donation was given in slightly more than half of these cases. In 42 per cent of the cases relatives were not aware of the attitude of the deceased, and in 40 per cent of these cases they used their right of veto against organ donation. Corresponding registration, as part of the computerised system for quality assurance for intensive care (PASIVA), may become a national and complete quality assurance for organ donation in Sweden.
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| 3. |
- Andersson, Helene, et al.
(author)
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Calcineurin inhibitor minimisation in renal transplantation
- 2008
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In: European Journal of Hospital Pharmacy Practice. - 1781-9989. ; 14:6, s. 49-51
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Journal article (peer-reviewed)abstract
- Calcineurin inhibitor toxicity is a major reason for long-term graft loss (chronic rejection). Here is a snap shot of the ongoing quest to balance continuing efficacy against toxicity.
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| 4. |
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| 5. |
- Bruun, Laila, et al.
(author)
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Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplantation.
- 2004
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 171:4, s. 1432-1435
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Journal article (peer-reviewed)abstract
- PURPOSE: The low molecular mass and short half-life of free (f) prostate specific antigen (PSA) implies elimination from blood by glomerular filtration. In addition, patients with terminal renal failure have increased fPSA in serum but there have been sparse data reported on the rates and pathways of elimination of PSA complexes and human kallikrein 2 (hK2). We studied glomerular filtration dependent elimination of fPSA and hK2 in patients with renal insufficiency undergoing successful renal transplantation.MATERIALS AND METHODS: We studied 14 patients with immediate onset of renal function after renal transplantation. Blood samples were obtained before and at regular intervals up to 160 hours after transplanted kidney reperfusion. Measurements of fPSA, total PSA and hK2 were performed with immunofluorometric assays and complexed PSA was determined by a chemiluminiscence assay. Glomerular filtration rates were monitored by analyzing serum creatinine and cystatin C. NONMEM, a multivariate pharmacokinetic approach, was used to determine the elimination rates of fPSA and hK2 after renal transplantation.RESULTS: Serum fPSA and hK2 but not PSA complexes, decreased rapidly after renal transplantation. Significant reductions in fPSA and hK2 were observed after only 16 and 8 hours, respectively. fPSA and hK2 showed similar elimination patterns, decreasing to 42% and 44% of their original levels compared to cystatin C, which was at 44% after 160 hours. The median half-lives of fPSA and hK2 were 17.4 and 11.5 hours, respectively.CONCLUSIONS: These results verify the hypothesis that fPSA and hK2 are eliminated from the blood circulation by glomerular filtration and severe renal failure influences the levels of the 2 proteins in serum.
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| 6. |
- Chen, Jibing, et al.
(author)
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An N-(alkylcarbonyl)anthranilic acid derivative prolongs cardiac allograft survival synergistically with cyclosporine A in a high-responder rat model
- 2010
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In: Transplant Immunology. - : Elsevier BV. - 1878-5492 .- 0966-3274. ; 23:4, s. 180-184
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Journal article (peer-reviewed)abstract
- We investigated the immunosuppressive effects of the dihydroortate dehydrogenase (DHODH) inhibitor compounds ABR-222417 and ABR-224050 from Active Biotech (Sweden). We verified the inhibitory effects of these compounds on the proliferation of CD4(+) and CD8(+) T-cells in vivo by using superantigen staphylococcus enterotoxin A (SEA)-mediated proliferation test. To evaluate their efficacy, the compounds were screened in a low-responder heart allograft transplantation model in rats [heart from Piebald Virol Glaxo (PVG) transplanted to Dark Agouti (DA)]. The immunosuppressive effects of the compounds were then investigated in a high-responder model (DA to PVG). Treatment with ABR-222417 (30 mg/kg) was more efficient than that with ABR-224050 (10 mg/kg), and the former provided a longer graft median survival time (MST, 29.5 days) than the latter (MST, 18.5 days). Furthermore, there was a marked increase in graft survival time (53 days) when low doses of ABR-222417 and cyclosporine A (CsA) were used in combination. No sign of tolerability problems was detected using this combination or when ABR-222417 was used singly at a higher dose. Furthermore, T-cell proliferation studies in vitro support that the anti proliferative effect of ABR-222417 is caused by inhibition of de novo pyrimidine synthesis, which is the consequence of DHODH inhibition. These results show that ABR-222417 had marked immunosuppressive effects on the heart allograft transplantation and that it exerts an even more powerful inhibitory effect on graft rejection when used in combination with CsA, with good tolerability. (C) 2010 Elsevier B.V. All rights reserved.
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| 7. |
- Cippà, Pietro E, et al.
(author)
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Risk Stratification for Rejection and Infection after Kidney Transplantation.
- 2015
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In: Clinical Journal of the American Society of Nephrology. - 1555-905X. ; 10:12, s. 2213-2220
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Journal article (peer-reviewed)abstract
- Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation.
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| 8. |
- Claes, Kathleen, et al.
(author)
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Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study
- 2012
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:2, s. 850-857
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Journal article (peer-reviewed)abstract
- The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation. Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm. The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm. This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.
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| 9. |
- Colom, Helena, et al.
(author)
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Pharmacokinetic modeling of enterohepatic circulation of mycophenolic acid in renal transplant recipients.
- 2014
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 85:6, s. 1434-1443
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Journal article (peer-reviewed)abstract
- Several factors contribute to mycophenolic acid (MPA) between-patient variability. Here we characterize the metabolic pathways of MPA and quantify the effect of combining genetic polymorphism of multidrug-resistant-associated protein-2, demographics, biochemical covariates, co-medication (cyclosporine (CsA) vs. macrolides), and renal function on MPA, 7-O-MPA-glucuronide (MPAG), and acyl-glucuronide (AcMPAG) disposition, in renal transplant recipients, after mycophenolate mofetil. Complete pharmacokinetic profiles from 56 patients (five occasions) were analyzed. Enterohepatic circulation was modeled by transport of MPAG to the absorption site. This transport significantly decreased with increasing CsA trough concentrations (CtroughCsA). MPAG and AcMPAG plasma clearances significantly decreased with renal function. No significant influence of multidrug-resistant-associated protein-2 C24T single-nucleotide polymorphism was found. The model adequately predicted the increase in MPAG/AcMPAG exposures in CsA and macrolide patients with decreased renal function. This resulted in higher MPA exposures in macrolide patients versus CsA patients, and increased MPA exposures with renal function from 25 to 10 ml/min, in macrolide patients, owing to enhanced MPAG enterohepatic circulation. Lower-percentage enterohepatic circulation occurred with higher CtroughCsA and renal function values. The lack of MPA protein-binding modeling did not permit evaluation of the impact of renal function and CtroughCsA on MPA exposures in CsA patients. Thus, dose tailoring of covariates is recommended for target MPA exposure.Kidney International advance online publication, 8 January 2014; doi:10.1038/ki.2013.517.
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| 10. |
- Corbascio, Matthias, et al.
(author)
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CTLA4Ig combined with anti-LFA-1 prolongs cardiac allograft survival indefinitely.
- 2002
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In: Transplant Immunology. - 1878-5492. ; 10:1, s. 55-61
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Journal article (peer-reviewed)abstract
- CTLA4Ig and anti-LFA-1 are members of a new generation of immunomodulatory drugs which inhibit important signaling pathways in T cell activation. Both substances target molecules which have pivitol functions in the activation of CD4+ and CD8+ T cells and have been theorized to have an interdependent relationship. These drugs have been used independently in various treatment regimens and have shown great promise in prolonging the survival of allografts. In order to test whether these substances have synergistic or potentiating effects when combined, we performed mixed lymphocyte reactions, skin transplantation and vascularised heterotopic heart transplantation in the Balb/c (H-2(d)) to C3H/HeJ (H-2(k)) strain combination. When anti-LFA-1 and CTLA4Ig were combined at low doses, there was a substantial inhibition of lymphocyte proliferation. When each drug was used as a mono-therapy in skin graft recipients, there was no significant effect on median graft survival (anti-LFA-1, 15 days; CTLA4Ig, 16 days) when compared to untreated controls (13 days), whereas a combination of anti-LFA-1 and CTLA4Ig extended graft survival significantly to 32 days. Untreated vascularised heart grafts rejected at a median of 8 days, CTLA4Ig-treated mice rejected at a median time of 79 days and anti-LFA-1-treated mice rejected at 43 days (n = 9). When CTLA4Ig and anti-LFA-1 were combined, all animals had functioning heart grafts at 100 days after transplantation. Histological analysis of combined-therapy hearts showed no signs or only minor changes associated with chronic rejection. In conclusion, these results indicate a synergistic effect of combining anti-LFA-1 with CTLA4Ig in inhibiting lymphocyte proliferation and prolonging the survival of fully MHC-mismatched allografts.
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