摘要:

Background.The aim of this systematic review was to compare the safety and efficacy of laparoscopic live donor nephrectomy with the “gold” standard of open live donor nephrectomy.Methods.Search strategy: Three search strategies were devised to enable literature retrieval from the Medline, Current Contents, Embase, and Cochrane Library databases up until, and including, February 2000.Study selection: Inclusion of a report was determined on the basis of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. English language reports were selected and acceptable study designs included randomized-controlled trials, controlled clinical trials, case series, or case reports. Each report was required to provide information on at least one of several safety and efficacy outcomes as detailed in the protocol.Data collection and analysis: Twenty-five reports met the inclusion criteria. They were tabulated and critically appraised in terms of the methodology and design, sample size, outcomes, and the possible influence of bias, confounding, and chance.Results.High level evidence comparing the safety and efficacy of laparoscopic live donor nephrectomy with open donor nephrectomy was not available at the time of this review. Limited low level evidence suggested that the laparoscopic approach might be advantageous regarding the donor’s hospital stay, convalescence, pain, and resumption of employment.Conclusions.The ASERNIP-S Review Group concluded that the evidence-base for laparoscopic live donor nephrectomy was inadequate to make a safety and efficacy recommendation. Clinical and research recommendations were developed regarding the introduction and current practice of this procedure in Australia.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Gal&agr;1-3Gal epitopes in porcine tissue, initiate this phenomenon.Methods and results.Specific depletion of anti-Gal&agr;1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Gal&agr;1-3Gal&bgr;1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gal&agr;1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation.Conclusion.These results demonstrate that anti-Gal&agr;1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients.Methods.Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays.Results.The yield of RdD cells ranged from 0.1 to 0.9% of the starting material with the majority being TcR&agr;&bgr;, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 2–3 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated allogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells.Conclusions.These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Graft versus host disease (GVHD) prevents potentially curative allogeneic stem cell transplantation from being offered to cancer patients who lack a suitably matched donor. New methods to prevent GVHD are required to allow successful transplants across major histocompatibility complex barriers.Methods.A model of GVHD in C.B-17 SCID mice was developed to allow the study of allo-activated donor T cells without confounding effects of host lymphocytes. The abilities of cyclosporin-A, anticytokine antibodies, and oxidative stress to prevent GVHD in this model was studied.Results.T cells from major histocompatibility-mismatched donor mice caused severe GVHD in sublethally irradiated SCID hosts that could be ameliorated by coadministration of donor bone marrow but not by cyclosporine-A or anticytokine antibodies. In contrast, three-log more T cells could be injected without clinical consequences if they had been pretreated with a combination of heat, ultraviolet light, and oxygenation. The effect was not the trivial result of donor T cell destruction because T cell reconstitution, although delayed, recovered to normal levels within 2 weeks. Protection from GVHD required oxygenation and was associated with normalization of the CD4/CD8 donor T cell ratio, recovery of host hematopoiesis, and decreased inflammatory cytokine production.Conclusion.Pretreatment of donor T cells with a combination of physicochemical stressors effectively prevents GVHD caused by major major histocompatibility disparities and may facilitate the safe transplantation of patients without HLA-identical donors.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Increased expression of heat shock proteins (HSPs) was assumed during cardiac allograft rejection. To find evidence for this in man, we quantified HSP27 and HSP72 in cardiac allograft biopsies.Methods.In parallel to histological assessment of rejection, HSP27 was quantified by Western blotting in a total of 43 biopsies sampled from 3 patients. HSP72 was analyzed in parallel in 30 of the 43 cases. For comparison, HSPs were analyzed in myocardium.Results.HSP27 was significantly higher in rejecting cardiac allografts than in non-rejecting allografts and non-failing myocardium (1.52±0.25 vs. 0.83±0.11 vs. 0.50±0.05 &mgr;g/mg protein). Similarity for HSP72 (6.27±1.54 vs. 4.06±1.03 vs. 6.27±0.76 &mgr;g/mg protein) was not found.Conclusion.For the first time in humans with cardiac allograft rejection, increased expression of HSP27, which could be important for cardiac self-protection, was demonstrated. For the lack of increased HSP72 expression, the influence of the cyclosporine A treatment was discussed.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.When adults are transplanted with segmental grafts, disparity between the size of the graft and the native organ is almost universal.These grafts presumably still receive all of the native portal inflow despite a reduced vascular bed and dramatically elevated blood flow may result. The hemodynamic changes after segmental transplantation in adults have not yet been studied and their clinical significance is unknown.Methods.Portal venous and hepatic arterial blood flow were measured intraoperatively in right lobe liver donors and recipients with electromagnetic flow probes. Postoperative evolution was monitored in recipients with ultrasonography.Results.Portal flow to the right lobe ranged from 601 to 1102 ml/min before resection and from 1257 to 2362 ml/min after transplantation. There was a statistically significant linear correlation between the change in portal flow and graft to recipient body weight ratio. Arterial blood flow ranged from 213 to 460 ml/min before resection and from 60 to 300 ml/min after transplantation. Preoperative portal peak systolic velocity was uniformly around 10 cm/sec. Values on postoperative day 1 were increased to 30 cm/sec in recipients of cadaveric organs, to 50 cm/sec in recipients of organs with graft to recipient body weight ratios of more than 1.2%, and to 115 cm/sec in recipients of organs with ratios less than 0.9%. A decreasing tendency was universally observed. Arterial systolic velocity was inversely related to portal systolic velocity. Neither graft dysfunction nor vascular complications occurred.Conclusions.The hemodynamic pattern after right lobe transplantation is predictable and intraoperative measurements and ultrasonography are useful for monitoring. The size of the graft influences the magnitude of the hemodynamic changes.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified.Methods.During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age <30, n=7), middle-aged donor group (group M, 30≤donor age <50, n=13), and older donor group (group O, donor age<50, n=6). Early allograft function and regeneration were compared between these groups.Results.There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups.Graft and patient survival were comparable between the three groups.Conclusion.Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.HuM291 is a humanized anti-CD3 monoclonal antibody engineered to reduce binding to Fc&ggr; receptors and complement fixation.HuM291 has a long serum half-life and mediated profound depletion of circulating T cells in chimpanzees; HuM291 also has significantly less mitogenic and cytokine-releasing activity than OKT3 in vitro.Methods.A phase I dose-escalation study was conducted in 15 end-stage renal disease patients scheduled for renal allografts from living donors. Patients received one i.v. HuM291 injection before transplantation. Five doses were tested: 0.015 &mgr;g/kg, 0.15 &mgr;g/kg, 0.0015 mg/kg, 0.0045 mg/kg, and 0.015 mg/kg. Patients were followed for adverse events, laboratory abnormalities, serum cytokine levels, pharmacokinetics, and CD2+, CD3+, CD4+, and CD8+T cell counts.Results.HuM291 was well tolerated; most adverse events were mild to moderate in severity and included headache, nausea, chills, and fever. These occurred within the first few hours after HuM291 administration, resolved within 24 to 48 hr, and were likely related to cytokine release. In general, peak tumor necrosis factor-&agr;, interferon-&ggr;, and interleukin-6 levels were detected 1 to 6 hr postdosing only at the three highest doses and were generally undetectable by 24-hr postdosing. Serious adverse events possibly related to HuM291 included clotting of a fistula (two patients), chemical cellulitis (one patient), and increased serum creatinine/decreased hematocrit (one patient). At doses ≥0.0015 mg/kg (0.1 mg/70 kg), HuM291 induced rapid, marked depletion of peripheral T cells within 2 hr; duration of T cell depletion was dose dependent. At the two highest dose levels, T cells remained depleted for approximately 1 week.Conclusions.A single HuM291 dose rapidly depleted circulating T cells in a dose-dependent manner and was associated with only mild to moderate symptoms of cytokine release.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.We prospectively assessed the safety of kidney transplantation into continent urinary intestinal reservoirs as a planned two-stage procedure in patients with absent or dysfunctional lower urinary tract.Methods.Between November 1990 and June 1999, 12 patients have undergone renal transplantation into continent urinary reservoirs, and a further patient with a diversion is awaiting transplantation. This was part of a larger series of 356 patients who had undergone continent diversions during that period. A further 174 patients (33%) had diversions into ileal conduits.Findings.Within a mean follow-up of 26.1 months (5–72) after transplantation renal function was stable with serum creatinine values ranging from 0.9 to 1.8 mg/dl. There were 5 reoperations in the 12 patients (40%). Two patients needed their continence mechanism replaced. One had renal vein thrombosis with loss of the transplant. The cause for this was unknown but it had been speculated that it could have been caused by graft/body size disproportion. A second kidney was successfully transplanted after 12 months. Two further revisions were required for ureteric kinking and lymphocele. The patient with orthotopic substitution voids to completion. The other patients are continent day and night with easy catheterization.Interpretation.This is one of the largest single series reported to date of renal transplantation into continent urinary diversions, and we commend the approach in carefully selected patients, but the difficulties must not be underestimated and the specific problems of intestinal urinary reservoirs have to be reckoned with. These procedures should be confined to centers with considerable experience with this type of surgery and its complications. Lifelong close surveillance is critical for the success of this concept.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The increasing use of tacrolimus as a primary immunosuppressant is paralleled by a growing number of pregnancies occurring in mothers receiving tacrolimus systemically.Methods.In this retrospective analysis during 1992–1998; data sources were case reports from clinical studies, spontaneous reports from health care professionals, routine surveys by transplant registries, and the published literature.Results.One hundred pregnancies in 84 mothers were recorded. Mean maternal age was 28 years. All except one mother (autoimmune disease) were solid organ transplant recipients (66% liver and 27% kidney). Mean time from transplantation to conception was 26 months. The mean daily dose of tacrolimus (range 11.7–12.8 mg/day) and the mean tacrolimus whole blood level (range 8.5–11.5 ng/ml) remained fairly constant from preconception through the third trimester. The most frequent maternal complications were graft rejection followed by preeclampsia, renal impairment, and infection. All cases of rejection were successfully treated with corticosteroids and did not result in graft loss. Of 100 pregnancies, 71 progressed to delivery (68 live births, 2 neonatal deaths, and 1 stillbirth), 24 were terminated (12 spontaneous and 12 induced), 2 pregnancies were ongoing, and 3 were lost to follow-up. Mean gestation period was 35 weeks with 59% deliveries being premature (<37 weeks). The birth weight (mean 2573 g) was appropriate for gestational age in 90% of cases. Most common complications in the neonate were hypoxia, hyperkalemia, and renal dysfunction. These were transient in nature. Four neonates presented with malformations, without any consistent pattern of affected organs.Conclusion.Pregnancy in tacrolimus-treated transplant recipients resulted in a favourable outcome. Complications of the mother and neonate were similar to those previously described with other immunosuppressants.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID