ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundIschemic injury of the microvascular endothelium during cold preservation causes a disturbance of vascular microcirculation after reperfusion and results in graft failure. Recently we have shown that oxygenation of the canine pancreas during preservation by the two-layer method extends the period of preserved pancreatic viability. The aim of this study was to clarify the role of the oxygenation of the pancreas graft by the two-layer method in the viability of the microvascular endothelium during preservation.MethodsAfter preservation of the canine pancreas by simple cold storage in Euro-Collins solution (EC) (group 1) or by the two-layer method using EC (group 2) for 48 hr, the viability of vascular endothelial cells was judged from nuclear trypan blue uptake. Pancreatic tissue perfusions were measured with a hydrogen gas clearance technique, and graft survival rates were examined after autotransplantation. In the control group, the grafts were autotransplanted without preservation (group 3).ResultsGraft survival rates were 0 of 5 (0%), 5 of 5 (100%), and 5 of 5 (100%) in groups 1, 2, and 3, respectively. The percentage of trypan blue-positive vascular endothelium in group 1 was significantly higher compared with group 3 (control) (26.4±1.7 vs. 7.4±4.3%,P<0.01). The two-layer method (group 2) decreased trypan blue uptake (11.3±3.7 vs. 26.4±1.7%,P<0.01). Pancreatic tissue perfusions after 2 hr of reperfusion were in inverse proportion to trypan blue uptake. Namely, pancreatic tissue perfusions in group 1 were significantly lower than group 3 (control) (45.6±12.8 vs. 64.5±20.6 ml/min/100 g,P<0.01). The two-layer method (group 2) improved pancreatic tissue perfusions (68.8±8.6 vs. 45.6±12.8 ml/min/100 g,P<0.01).ConclusionWe conclude that oxygenation of the pancreas during preservation by the two-layer method protects the microvascular endothelium from cold ischemic injury. Consequently, pancreatic microcirculation can be maintained after reperfusion, thus extending the period of preserved pancreatic viability.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundCurrent insulin therapies for control of glucose metabolism in patients with type I diabetes mellitus prevent major metabolic consequences of insulin deficiency, but none prevents or arrests longterm complications. In experimental models of canine diabetes, retinopathy, neuropathy, and nephropathy have been shown to develop within 5 years. The aim of this study was to determine in a canine model whether glucose control provided by segmental duct-occluded pancreas autografts could prevent the long-term complications of diabetes.MethodsThirty-five outbred mongrel dogs underwent segmental pancreas autotransplantation with residual pancreatectomy. Follow-up over 5 years included endocrine, retinal fundus photography, fluorescein angiography, and nerve conduction studies. At endpoint, analysis of organ specific changes was undertaken.ResultsLong-term survival was achieved in 14 dogs for 4 to 5 years and in 3 dogs for 3 to 5 years. Glycosylated hemoglobin levels remained within normal limits, although response to glucose challenge was suboptimal. Fundus photography and fluorescein angiography demonstrated the absence of retinal vascular aneurisms, capillary leakage, and obliteration. Retinal digest showed no vascular changes and normal endothelial/pericyte ratios. Nerve conduction was normal, and histology of nerves revealed normal density of myelinated fibers and absence of intrafascicular vessels and glycogen deposits, with no change in spectrum of fiber diameters and ovoids. Renal histology revealed no evidence of nephropathy with normal glomerular basement membranes.ConclusionsWe have demonstrated that duct-occluded segmental pancreatic autografts are capable of providing satisfactory metabolic control for up to 5 years, thereby preventing development of the longterm microvascular complications of diabetes.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundRejection is the major barrier preventing the more widespread application of intestinal transplantation as treatment for intestinal failure. For this study, a one-way host-versus-graft murine model was used to investigate the contribution of T cell subsets to the rejection of allogeneic intestinal allografts.MethodsIntestinal grafts consisting of the donor jejunum and ileum were procured from C57BL/6J (syngeneic group) and B6C3F1/J (C57BL/6 × C3H/HeJ, allogeneic group) mice. These grafts were then transplanted into (1) normal, (2) antibody-treated, or (3) genetically mutated C57BL/6 mice. Mice were killed at predetermined intervals and the grafts assessed for rejection by a blinded pathologist.ResultsNo syngeneic mice demonstrated any evidence of rejection. In contrast, the recipients of allografts experienced progressive rejection. Recipient mice treated with tacrolimus developed significantly less severe allograft rejection. None of the αβ T cell-deficient recipient mice (T cell receptor β chain knockout mice) experienced allograft rejection with follow-up ranging from 8 to 28 days. However, mice deficient in γδ T cells (T cell receptor δ chain knockout mice) rejected intestinal allografts in a manner indistinguishable from normal recipients. In order to investigate the role of CD4+and CD8+T cells, recipient mice were treated 2 days before transplantation with depleting monoclonal antibodies specific for either CD4+cells or CD8+cells. Depletion of either population of cells significantly inhibited allograft rejection.ConclusionsThese data demonstrate that rejection of intestinal allografts in the murine model was absolutely dependent on αβ but not γδ T cells. Furthermore, both CD4+and CD8+T cells were necessary for small bowel allograft rejection. Additional studies will be required to determine whether the effects of monoclonal antibody treatment were due solely to depletion of T cells or were mediated at least in part through an active process that altered the functional properties of the targeted T cell subset.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundAntiadhesion therapy using monoclonal antibodies (mAbs) to adhesion molecules in vivo has been shown to produce significant prolongation of graft survival in various transplantation models. However, it remains unclear whether antiadhesion therapy operates by merely blocking adhesion between antigen-presenting cells and T cells physically and/or by blocking contimulatory signals while preserving signals mediated through T-cell receptors in vivo. We examined antigen-specific T-cell responses during and after antiadhesion therapy.MethodsBALB/c islets were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice given anti-lymphocyte function-associated antigen (LFA)-1 and/or anti-intercellular adhesion molecule-1 mAb treatment. The animals bearing surviving islet allografts were challenged with BALB/c or third-party islets on day 7 or more than 100 days after transplantation.ResultsIslet allografts were acutely rejected in untreated animals, with a mean survival time (MST) of 19±8 days. Administration of anti-LFA-1 mAb induced significant prolongation of graft survival with a mean survival time of 72±33 days, and half of the allografts showed indefinite survival. The animals given anti-LFA-1 mAb alone 7 days before transplantation showed acute rejection of BALB/c islets, whereas a significant number of animals given anti-LFA-1 mAb and the BALB/c islet allograft simultaneously accepted secondary BALB/c islets, but rejected third-party islets. Likewise, most of the animals bearing long-term functioning BALB/c allografts for more than 100 days accepted secondary BALB/c islets, but rejected C3H islets acutely. Interestingly, the spleen cells from these animals transferred unresponsiveness to BALB/c islets into the 2.5-Gy x-irradiated recipients, whereas those from naive animals induced acute rejection.ConclusionsThese results indicate that anti-LFA-1 mAb treatment prevents T-cell activation leading to rejection, but results in a T-cell receptor engagement leading to antigen-specific unresponsiveness maintained by transferrable suppressor cells.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe purpose of this study was to compare the efficacy of histidine-tryptophan-ketoglutarate (HTK) solution after prolonged cold storage with that of the conventional glucose-insulin-potassium (GIK) and University of Wisconsin (UW) solutions in experimental heart preservation. GIK solution was chosen as a control to mimic current clinical regimens. Variables of cardiac function, myocardial tissue water, and adenine nucleotide pool metabolites were used to assess prolonged myocardial preservation in the isolated rat heart model.MethodsHearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline cardiac function. The hearts were divided into three groups (n=6 per group) according to each preservation solution used: group 1, GIK solution; group 2, UW solution; and group 3, HTK solution. The hearts were then arrested and stored in each solution for 6, 8, and 12 hr at 4°C. After storage, the hearts were reperfused and recovery of cardiac function and myocardial tissue water content were evaluated. Myocardial adenylate contents just after storage in each group (n=5 hearts/group) were also measured.ResultsThe hearts stored in HTK solution showed maintenance of cardiac function at up to 8 hr of almost 80% of prepreservative baseline function; however, recovery of cardiac function of the hearts stored in UW solution revealed an initial loss of function at 6 hr of almost 60% and a decline to 50% at 8 hr. Furthermore, recovery of cardiac function of the hearts stored in GIK solution revealed a progressive loss of function at 6 hr of storage of almost 50% and a decline to 30% at 8 hr of storage. The myocardial ATP/ADP ratios after 6 hr of storage in HTK and UW solutions were significantly higher than the ratio found in GIK solution. Although the myocardial ATP/ADP ratio after 8 hr of storage in HTK solution was maintained above 50%, the ratios in GIK and UW solutions declined to 15%. In addition, the myocardial energy charge values of the hearts stored in HTK solution were sufficiently maintained until 8 hr of storage, whereas the values in UW and GIK solutions declined to below 50% at 6 hr of storage and 20% at 8 hr of storage. Although there were no significant differences in tissue water contents after 6 and 8 hr of storage among the three groups, the water contents of the hearts after 12 hr of storage in HTK and UW solutions were significantly lower than that of the hearts stored in GIK solution.ConclusionsOur results suggest that HTK solution is much more effective than UW and GIK solutions for isolated rat heart preservation; however, successful cold storage of the heart is highly energy-dependent, and a dramatic breakdown of myocardial energy level, which causes a crucial decline in cardiac function, occurs between 8 and 12 hr of storage.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundA very important issue in living kidney donor transplantation is whether the donation is safe for the donor1,2,3,4. The aim of this study was to examine survival and causes of death in kidney donors and to assess the renal function in those who had donated a kidney more than 20 years ago.MethodsA total of 459 living donor nephrectomies were performed in Stockholm from 1964 until the end of 1994. By using national registers, all 430 donors living in Sweden were traced. Donor survival was analysed using the Kaplan-Meier method. Expected survival was computed using the Hakulinens method and was based on national mortality rates.ResultsForty-one subjects had died between 15 months and 31 years after the donation. The mortality pattern was similar to that in the general population, the majority dying of cardiovascular diseases and malignancies. After 20 years of follow-up, 85% of the donors were alive, whereas the expected survival rate was 66%. Survival was thus 29% better in the donor group. One third of the donors (aged 46-91 years) who had donated >20 years ago had hypertension. There was a deterioration in the renal function with increasing age, similar to what is seen among normal healthy subjects. The average glomerular filtration rate in donors aged 75 years and over was 48 ml/min/1.73 m2.ConclusionsTo donate a kidney does not seem to constitute any long-term risk. The better survival among donors is probably due to the fact that only healthy persons are accepted for living kidney donation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundRetrospective studies on the prevalence of posttransplant diabetes mellitus (PTDM) in patients on triple-drug immunosuppressive therapy have shown great dispersity, while the incidence of posttransplant impaired glucose tolerance (IGT) is unknown. The aim of our study was to prospectively examine the incidence of posttransplant glucose intolerance and to assess potential risk factors.MethodsGlucose intolerance was prospectively examined in 173 consecutive kidney transplant recipients by oral glucose tolerance tests (n=167) or the diagnosis of manifest diabetes mellitus (n=6) at 10 weeks after transplant.ResultsWe found a high incidence of PTDM (18%) and IGT (31%). Univariate analysis revealed that age, family history of diabetes, HLA-B27 phenotype, DR mismatch, rejection, actual prednisolone dose, total methylprednisolone dose, total steroid dose, cytomegalovirus (CMV) infection, and the use of furosemide were associated with PTDM. Age, prednisolone dose, CMV infection, and the use of beta-blockers were associated with IGT. Gender, body mass index, donor source, and cyclosporine level did not influence glucose tolerance. Prednisolone dose, age, family history of diabetes, CMV infection, and HLA-B27 phenotype were independent predictors of PTDM with the use of multiple stepwise logistic regression analysis. Age, prednisolone dose, and the use of a beta-blocker were associated with IGT in the multivariate model. Both univariate and multivariate linear regression analysis revealed a significant relationship between the 2-hr serum glucose and prednisolone dose. The risk of developing PTDM was 5% per 0.01 mg/kg/day of increase in prednisolone dose.ConclusionsIncreased prednisolone dose and older age are strongly associated with the development of posttransplant glucose intolerance.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundAllocation of cadaver kidneys by graded human leukocyte antigen (HLA) compatibility scoring arguably has had little effect on overall survival while prejudicing the transplant candidacy of African-American and other hard to match populations. Consequently, matching has been proposed of deduced amino acid residues of the individual HLA molecules shared by cross-reactive antigen groups (CREGs). We have examined the circumstances under which compatibility with either method impacted graft survival.MethodsUsing Cox proportional hazards regression modeling, we studied the relationship between levels of conventional HLA mismatch and other donor and recipient factors on primary cadaver kidney survival between 1981 and 1995 at the University of Pittsburgh (n=1,780) and in the United Network for Organ Sharing (UNOS) Scientific Registry during 1991-1995 (n=31,291). The results were compared with those obtained by the matching of amino acid residues that identified CREG-compatible cases with as many as four (but not five and six) HLA mismatches.ResultsWith more than one HLA mismatch (>85% of patients in both series), most of the survival advantage of a zero mismatch was lost. None of the HLA loci were “weak.” In the UNOS (but not Pittsburgh) category of one-HLA mismatch (n=1334), a subgroup of CREG-matched recipients (35.3%) had better graft survival than the remaining 64.7%, who were CREG-mismatched. There was no advantage of a CREG match in the two- to four-HLA incompatibility tiers. Better graft survival with tacrolimus was observed in both the Pittsburgh and UNOS series.ConclusionsObligatory national sharing of cadaver kidneys is justifiable only for zero-HLA-mismatched kidneys. The potential value of CREG matching observed in the one-HLA-mismatched recipients of the UNOS (but not the Pittsburgh) experience deserves further study.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundThe Banff Schema suggests the term “borderline changes” for biopsies showing changes insufficient for a diagnosis of mild acute rejection. The appropriate clinical management for patients showing such changes on biopsy is controversial.MethodsWe reviewed the clinical course and response to antirejection therapy of 24 patients with borderline changes, and compared our findings with those obtained from 14 patients with mild acute rejection. Patients were classified as showing complete response, partial response, or no response to antirejection treatment, depending on whether the posttreatment fall in serum creatinine was >70%, 30-70%, or <30% of the pretreatment rise, respectively. Renal allograft biopsies were systematically evaluated in accordance with the Banff schema.ResultsComplete response to antirejection therapy was seen in 15/24 (63%), partial response in 3/24 (13%), and nonresponse in 6/24 (25%) patients with borderline change. Compared with patients showing complete response, nonresponse was associated with higher scores of acute tubular necrosis and chronic allograft nephropathy (P<0.05). By comparison, 12/14 (86%) cases of mild acute rejection showed complete response to antirejection therapy (P=0.25 vs. patients with borderline change), and lack of response was associated with a higher score for chronic allograft nephropathy.ConclusionWhen biopsies are done in the context of renal allograft dysfunction, borderline changes frequently require increased immunosuppression. These findings should not be extrapolated to protocol biopsies performed in the setting of stable graft function.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID