ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Immunologically priviledged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect a xenograft from rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL.Methods.Based on the tetracycline-regulated expression system, constructs were designed that allow endothelial cell-specific and regulated expression of FasL by placing the tetracycline-dependent transactivator under control of the murine intercellular adhesion molecule-2 promoter.Results.Primary bovine endothelial cells transfected with FasL efficiently killed Fas-expressing cells in a regulated manner. Not only Fas-positive cell lines but also human peripheral blood lymphocytes underwent apoptosis upon exposure to FasL-transfected endothelial cells.Conclusion.This in vitro model may provide tools for the generation of transgenic animals to be used as donors for vascularized xenograft transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Recent studies have shown that the extent of platelet accumulation in the vasculature of transplanted organs correlates with the degree of preservation-reperfusion injury. In this study, we examined the effect of a stable prostacyclin analog, beraprost sodium, which possesses potent antiplatelet activity, on parameters of platelet accumulation and preservation-reperfusion injury of isografts in a rat model of lung transplantation.Methods.The heart-lung blocks of donor rats were flushed with and preserved in modified Euro-Collins solution at 4°C for 6 hr or 24 hr. The left lung was transplanted into recipient rats and reperfused for 1 hr. Lung injury was evaluated by the pulmonary blood flow ratios to the lung isografts, the weight gain of the isografts, and histological examination. Small portions of the lung isografts were excised and stained with an antibody specific for rat platelets. A scoring system was developed to semiquantitate the intensity of antibody staining (score 0-4). The recipient rats received oral administration of beraprost sodium (0.3 mg/kg) before lung transplantation. Control animals received no beraprost sodium.Results.In the 6-hr preservation study, administration of beraprost sodium significantly reduced the score for platelet accumulation (1.8±0.4 vs. 3.3±0.5,P<0.01). This observation was accompanied by a significantly decreased degree of preservation-reperfusion injury as evidenced by an increased blood flow ratio (13.7±2.6% vs. 4.5±3.6%,P<0.01) and a reduced weight gain (0.7±0.2 g vs. 1.1±0.2 g,P<0.01). Histological examination revealed severe capillary congestion in three of six cases in the control group, while no capillary congestion was observed in the beraprost group. In the 24-hr preservation study, no differences were seen in platelet accumulation scores or parameters of lung injury.Conclusion.Beraprost sodium, an antiplatelet agent, reduces platelet accumulation and preservation-reperfusion injury of lung transplants at 6 hr in this rat isograft model.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Histidine-tryptophan-ketoglutarate (HTK) has been used for experimental and clinical cardiac, renal, and liver transplantation. No experience exists in either experimental or clinical pancreas transplantation.Methods.In the present study, the solution was employed to flush segmental pancreatic grafts and to autotransplant the grafts after 24, 48, and 72 hr of cold storage in a porcine model. The results were compared to those obtained from animals receiving pancreatic grafts flushed and preserved with UW (University of Wisconsin) solution.Results.A total of 10 landrace pigs received a graft stored with HTK solution for 24 hr, and 6 animals received a graft stored with UW solution for 24 hr. Daily blood glucose levels were normoglycemic (i.e., blood glucose <150 mg/dl), and glucosuria was absent in all transplant animals. Intravenous glucose tolerance tests were comparable to two unoperated controls. Seven totally pancreatectomized, nontransplant diabetic controls exhibited daily hyperglycemia, glucosuria (i.e., > 1,000 mg/dl) and highly impaired intravenous glucose tolerance tests (meanK-values of -0.52±0.19 vs. -1.25±0.46 for HTK, -1.30±0.81 for UW, and -1.53±0.81 for controls,P-value vs. diabetic <0.01). The changes in wet weight between flushing and reperfusion were +2.22±2.84 g for HTK and -1.40±2.70 for UW stored grafts (P=0.034). After 48 hr of storage with HTK, 4/17 grafts were functioning and 1/11 recipients of grafts stored with UW were normoglycemic. All grafts stored for 72 hr in either HTK (n=3) or UW (n=3) uniformly failed to render the recipients normoglycemic.Conclusions.It is concluded that preservation of segmental pancreatic autografts for 24 hr with HTK solution provides reliable graft function, as does preservation with UW solution associated with an increase in wet weight after HTK preservation. Cold preservation with HTK and UW is feasible for 48 hr; however, the success rate is equally reduced with HTK and UW solution. Cold storage for 72 hr in either HTK and UW solution results in uniform graft failure in this model.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Quality of life is an important consideration in evaluating new medical or surgical treatments. Intestinal transplantation is now available for patients with irreversible intestinal failure. We compared quality of life among patients with intestinal failure receiving home parenteral nutrition (HPN) to that among patients who underwent intestinal transplantation (ITx) at the University of Pittsburgh Medical Center.Methods.The results of the Quality of Life Inventory, a self-administered questionnaire, were compared among 10 ITx recipients and 10 HPN patients. Change in quality of life was examined longitudinally over a 2-year period with repeat testing in four patients in each group.Results.ITx recipients were evaluated at mean time of 2.7 years after transplantation and after a mean period of 5.3 years of intestinal failure. HPN patients were evaluated after a mean period of 5.1 years of intestinal failure and were similar to the transplant recipients in age, gender, race, social status, education, etiology, and duration of disease. Assessed quality of life was markedly similar between HPN-dependent patients and ITx recipients, with significant differences in only 2 of 25 domains, despite the difficult early postoperative course and complex management that accompany intestinal transplantation. In longitudinal follow-up (n=4), ITx recipients reported significant improvement in anxiety (P=0.02), sleep (P=0.03), and impulsiveness/control (P<0.001), reflecting a progressive adjustment to their posttransplant status.Conclusion.The quality of life in ITx recipients is similar to that in HPN-dependent patients. Quality of life among ITx recipients improves over time with decreased anxiety over physical functioning. Further research and efforts to improve quality of life in transplant recipients are needed.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.The strong competition for scarce renal graft resources jeopardizes an individual patient's chances of a transplantation within a reasonable time scale. This study was undertaken to quantify these chances of receiving a transplant.Methods.All patients registered for their first renal allograft between January 1980 and December 1993 (n=40,636) in Eurotransplant4were selected. The influence of patient characteristics, such as age, HLA phenotype frequency, % panel-reactive antibodies, period of registration, and AB0 blood group, on the waiting list outflow was studied. The competing risk method was applied, and Poisson models were built to estimate the risk factor effects.Results.The chance of transplantation within 10 years after registration was overestimated by Kaplan-Meier (84%); using the competing risk method it was only 74%. The predicted chance for death on the waiting list was overestimated by 33% (45% Kaplan-Meier vs. 12% competing risk). A time-varying covariate effect on the chances of waiting list outflow was observed. Favorable factors for quick transplantation, such as blood group AB or a common HLA phenotype, were no longer seen to be driving forces for transplantation once 5 to 6 years of waiting time had been accrued.Conclusion.When multiple outcomes exist, Kaplan-Meier estimates should not be interpreted as survival rates, while competing risk estimates yield appropriate chances. A significantly decaying effect of the usual allocation parameters is observed with ongoing waiting time. This phenomenon is the statistical basis for redesigning allocation strategies. Organ exchange algorithms should have the potential to adapt to these time-varying effects.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.Upon the availability of a cadaveric donor kidney, a delicate allocation process precedes every transplantation. A remodeled Eurotransplant Kidney Allocation System (ETKAS)-derived from simulation studies-was installed in March 1996. The purpose was to adjust long waiting times and international exchange balances, while aiming at an optimal HLA-mismatch distribution. The new ETKAS consisted of a point-score system that was 100% patient oriented.Methods.The impact of the new ETKAS on the composition of the waiting list, and the outcome of the allocation procedures during its first year, were evaluated and compared with the results obtained in 1995.Results.The percentage of long-waiting patients and of patients with poorly matchable HLA phenotype increased significantly, from 9% to 19% and from 19% to 29%, respectively. Zero HLA-A-, HLA-B-, HLA-DR-mismatched patients still comprised 23% of the kidney transplant activity. The kidney exchange of the different Eurotransplant countries became balanced within 4 months; this persisted during the rest of the year. Pediatric patients had a high transplantation rate due to an assignment of extra points. The composition of the waiting list showed, after 1 year, fewer long-waiting patients and fewer patients with rare HLA phenotypes.Conclusions.The new ETKAS was able in its first year to meet the goals set at its introduction. In comparison with the old ETKAS, there was a better tradeoff between HLA matching and waiting time. The value of computer simulation studies has been demonstrated impressively in the context of organ allocation.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.With the aim of offsetting the reduction in donors of kidneys for transplantation, we extended the acceptance criteria, considering donors over 60 years old.Methods.The results obtained in 84 transplants carried out with this type of donor (group A) was compared with those of a control group of 125 transplants carried out with kidneys from donors under 60 years old (group B). The protocol for selection of donors was appropriate creatinine clearance, minimum proteinuria, and normal renal scan. The histological study was not included because it was not considered appropriate to assess the extent of the possible glomerulosclerosis, as this has a focal, segmented distribution. There were no significant differences between the recipients except for age (57.8 years old in group A vs. 39.2 years in group B).Results.After the transplantation, there were significant differences in the duration of hospitalization (26.8 days vs. 21.8 days,P<0.009), annual plasma creatinemia (177, 225, 233, 235, and 205 µmol/L vs. 136, 150, 121, 111, and 133 µmol/L,P<0.0002/0.0004), graft survival (87%, 85%, 81%, 81%, and 81% vs. 89%, 88%, 86%, 86%, and 85%,P<0.03), and patient survival (92%, 89%, 85%, 85%, and 85% vs. 99%, 99%, 97%, 96%, and 95%,P<0.0004). Death of the patient was the only significantly more frequent cause of graft loss among group A patients (7 vs. 1 death,P<0.004). No kidney was "never working" and none were lost because of chronic rejection.Conclusions.It was concluded that elderly donors should be considered as suitable for transplantation irrespective of their chronological age, provided that they fulfill the acceptance criteria. The quality of life achieved was comparable in both groups. Despite the lower renal function in group A, this remained constant during the follow-up period.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents.Methods.Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients.Results.Early mortality in this group was 11%; cumulative survival after 5 years was 74%.Conclusions.Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Background.The role of bone marrow-derived "passenger" leukocytes in the outcome of solid organ transplantation remains controversial. This study tested the relationship between high levels of donor-derived leukocytes within the transplanted organ and clinical outcome after lung transplantation.Methods.Sequential bronchoalveolar lavage samples were obtained from human lung allograft recipients. Leukocytes of donor origin in the bronchoalveolar lavage fluid were detected using two-color immunofluorescence, and the results were correlated with multiple clinical parameters.Results.Mean donor leukocytes levels for the first 200 days after transplantation were higher in patients with a good transplantation outcome compared with those patients who lost their grafts due to acute rejection (AR) or developed bronchiolitis obliterans syndrome. The presence of low numbers of donor-derived leukocytes for the first 200 days after transplantation was found to be a significant risk factor for graft loss due to either acute or chronic rejection (P=0.032). Nearly all patients (85%) experienced AR episodes. However, the time to onset of severe AR episodes was significantly longer (P=0.049), and the incidence of these episodes reduced, in patients who maintained high numbers of donor-derived leukocytes for the first 200 days after transplantation.Conclusions.The presence of high numbers of donor-derived leukocytes, particularly macrophages, in the transplanted lung in the first 200 days after transplantation was associated with stable graft function. Donor-derived leukocytes were reduced or absent in patients with a poor transplantation outcome. These findings rule out a negative influence of persisting donor leukocytes and are consistent with the emerging two-way models of transplant tolerance.

ISSN:0041-1337    

出版商:OVID    

年代:1998

数据来源: OVID