ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.This study evaluates whether surgical strategies such as the portosystemic shunt and ischemic preconditioning can protect against hepatic and pulmonary injury associated with liver transplantation.Methods.The effect of the portosystemic shunt, ischemic preconditioning, and both surgical procedures together were evaluated in rat liver transplantation. Alanine aminotransferase, hyaluronic acid levels in plasma, adenosine triphosphate and nucleotide levels in liver and edema, malondialdehyde levels, and myeloperoxidase activity were measured 24 hr posttransplantation. Plasmatic tumor necrosis factor (TNF) levels were measured as a possible proinflammatory factor responsible for hepatic and pulmonary damage associated with liver transplantationResults.Hepatocyte and cell endothelial damage were observed in liver grafts subjected to 8 hr of cold ischemia. This was associated with increased plasma TNF levels and lung inflammatory response. Portosystemic shunt application in the recipient protected endothelial cells but did not confer an effective protection from hepatocyte damage or reduce the increased plasma TNF levels and lung damage after liver transplantation. However, preconditioning of the donor liver conferred protection against both the endothelial cell and hepatocyte damage observed after liver transplantation. Preconditioning also attenuated the increased plasma TNF release and pulmonary damage. The combination of both surgical strategies resulted in levels of liver injury, TNF, and lung damage similar to those seen after liver transplantation.Conclusions.These findings indicate that ischemic preconditioning could be a preferred treatment to reduce hepatic and pulmonary damage associated with liver transplantation. However, this strategy may not be effective in several clinical situations requiring a portosystemic shunt.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.The ultimate goal of islet transplantation is the unlimited availability of insulin-secreting cells to be transplanted in a simple procedure that requires no use of immunosuppressive drugs. Immunoisolation of xenogeneic pig islets for transplantation has great potential therapeutic benefits for treatment of diabetes.Methods.Approximately 4×106porcine pancreatic endocrine cells (PEC) isolated from 6-month-old pigs were macroencapsulated in agarose-poly(styrene sulfonic acid) mixed gel and implanted into a prevascularized subcutaneous site in streptozotocin-induced C57BL/6 diabetic mice. Animals receiving an equal number of free porcine PEC were used as controls. After transplantation, nonfasting blood glucose, body weight, intraperitoneal glucose tolerance test, and immunohistologic evaluations were processed.Results.All 10 animals receiving the subcutaneous xenografts of the macroencapsulated porcine PEC normalized hyperglycemia within 5 days after transplantation, maintained the duration of normoglycemia for 24 to 76 days, and gradually gained weight. The subcutaneous xenografts of free porcine PEC could not reverse hyperglycemia. The recipient became hyperglycemic again when the implanted graft was retrieved at day 45 after transplantation. The glucose clearances were significantly ameliorated at day 21 and day 45 after transplantation when compared with those in diabetic mice. The immunohistochemical results revealed an inherent intact structure of the macroencapsulated porcine PEC and positive double-immunofluorescence staining for insulin and glucagon.Conclusions.Subcutaneous transplantation of macroencapsulated porcine PEC normalized hyperglycemia in diabetic mice. Our results identified a potential for a favorable development of subcutaneous transplantation of porcine PEC as a cure for diabetes.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.We investigated an approach to separating graft-versus-lymphoma (GVL) effects from graft-versus-host disease (GVHD) in mice receiving a nonmyeloablative conditioning regimen allowing establishment of mixed hematopoietic chimerism.Methods.We evaluated the ability of donor lymphocyte infusions (DLI) to mediate GVL effects without GVHD in mixed chimeras prepared with cyclophosphamide, anti–T-cell antibodies, and thymic irradiation. To examine the fate of GVH-reactive donor CD8+T cells, we used the 2C T-cell receptor (TCR) transgenic mouse strain, which carries an Ld-specific transgenic TCR on the B6 background.Results.Administration of DLI on day 35 post-BMT led to conversion from mixed to full donor chimerism and mediated a powerful GVL effect with complete protection (100% survival) against mortality induced by a host-type lymphoma (EL4) administered 7 days later (100% mortality in non-DLI controls;P<0.001). No GVHD occurred in DLI recipients. Rechallenging the surviving DLI recipients, which had converted to full chimerism, with the same tumor dose 17 weeks later led to rapid tumor mortality. Long-term DLI recipients had anti-host proliferative responses, but not CTL responses in vitro. When given as DLI together with wild-type spleen cells, marked expansion of GVH-reactive 2C CD8+T cells was observed on day 10, followed by a marked decline in their numbers by week 10 post-DLI.Conclusions.Nonmyeloablative induction of mixed chimerism followed by administration of DLI can mediate powerful GVL effects. The late loss of DLI-mediated GVL effects may reflect the eventual loss of donor-derived GVH-reactive CTL, which occurs in association with conversion to full donor chimerism.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Calcineurin-inhibitor nephrotoxicity plays a role in the pathogenesis of chronic allograft nephropathy by causing renal ischemia mediated by vasoconstrictive metabolites of the prostanoid pathway. The purpose of our study was to evaluate whether altering the prostanoid profile using juniper oil (JO) would afford renoprotection in rats treated with tacrolimus.Methods.Diets supplemented with biologic oils (no supplementation, JO, fish oil [FO], safflower oil [SO], and arachidonic acid [AA]) were fed to five groups of rats for 5 weeks; during the last 2 weeks, tacrolimus was administered to all groups except for a control group of animals. At week 5, urinary prostaglandin (PG)F2-&agr;and inulin clearances were measured. The rat kidneys were harvested to determine the renal cell membrane composition for arachidonic, eicosatrienoic, and eicosapentaenoic acids.Results.Both JO and FO completely reversed the decrease in inulin clearance seen with tacrolimus, the greatest effect being with JO (inulin clearance 15.1±3 vs. 6.0±1.1 ml/min in the nonsupplemented group;P<0.001); urinary PGF2-&agr;excretion was also highest in the JO group (328±23 pg/mL,P<0.001 vs. the nonsupplemented group). Fatty acid membrane analysis showed greatest incorporation of eicosapentaenoic and eicosatrienoic acids in the JO- (5.7±0.6% and 3.1±0.4%, respectively) and FO- (8.1±0.7% and 2.8±0.6%, respectively) treated animals.Conclusions.JO supplementation in tacrolimus-treated rats was associated with incorporation of vasodilatory prostanoids in the renal-cell membrane and elevated urinary PGF2-&agr;excretion, and the precipitous fall in inulin clearance induced by tacrolimus was completely prevented. Whether this benefit will translate into a reduction in chronic allograft nephropathy remains to be determined. However, our preliminary data point towards the need for human trials.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.We have previously reported on our 10-year experience of renal transplantation in children in the cyclosporine era, that is, from December 1981 until December 1991. In this paper, we report on the same children observed for another 10 years.Methods.Of 53 children who received a renal transplant between 1981 and 1991, 47 survived and were observed for 10 to 20 years. Immunosuppression consisted of cyclosporine, prednisolone, and azathioprine. Yearly clinical examinations were performed.Results.Overall, actual patient survival is 91%, 89%, and 89%, and actual graft survival 85%, 77%, and 66% at 1, 5, and 10 years, respectively. No patients have died during the last 10 years. Twenty-six grafts were lost over 20 years. Thirteen of those were lost during the present follow-up (10–20 years): 11 in chronic rejection and 2 because of development of renal cell carcinoma. No other malignancies were noted. Mean glomerular filtration rate decreased from 58±19 at 1 year (n=42) to 44±16 mL/min/1.73 m2body surface area at 10 (n=33) years. Hypertension was treated in 46%, 40%, and 66% of the children at 1, 5, and 10 years, respectively; two of them showed left ventricular hypertrophy 10 years after transplant. Minor cataracts without visual disturbance were found in 45% of patients. All children except three with mental retardation are, or have been, attending normal day care or normal school.Conclusion.Social integration is good, and severe complications are scarce, even when renal transplantation occurred at a very young age.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Deep venous thrombosis (DVT) tends to occur in greater frequency among cyclosporine (CsA)-treated renal-transplant recipients. Because administration of sirolimus may increase the whole-blood concentrations of CsA, we sought to assess the impact of the combination regimen on the incidence, predisposing factors, and consequences of postoperative DVT, transplant renal-vein or artery thrombosis, and pulmonary embolus.Methods.We retrospectively evaluated two cohorts of renal transplant recipients: CsA/prednisone (Pred)±azathioprine (n=136, group A) or sirolimus+CsA+Pred (n=354, group B) using Fisher’s exacttand chi-square tests, as well as Kaplan-Meier analyses, odds ratios, and multiple logistic regression methods.Results.The 7 of 136 (5.1%) incidence of thrombotic events in group A was similar to the 20 of 354 (5.6%) incidence in group B (P=0.513; NS) and occurred no more frequently ipsilateral to the transplant. Although the occurrence of an acute-rejection episode was not associated with the DVT diagnosis, all affected patients displayed elevated serum creatinine (Scr) values, which remained slightly higher than baseline following recovery (group A 1.63±1.22–1.95±0.93 mg/dL; group B 1.70±1.11–2.01±0.88 mg/dL). Renal biopsies failed to show evidence of intrarenal coagulopathy. No patient lost a graft as a complication of DVT, nor did these events produce other lasting adverse effects. Patients in the sirolimus group showed a strong correlation between the occurrence of DVT and the previous existence of an ipsilateral or contralateral lymphocele.Conclusion.Addition of sirolimus to a CsA+Pred regimen does not increase the incidence of postoperative thrombotic events among renal transplant recipients.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis.Methods.A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants compared with a background hospital incidence of 3.7%.Results.The spectrum of RBC alloantibodies in Chinese patients was different than in white patients, with no anti-D or anti-K antibodies but a significant incidence of anti-Mi (29%) antibodies. There was a significantly increased incidence of transfusions in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft.Conclusions.Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as the result of difficult postoperative stabilization, especially in cases requiring massive transfusion.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background.Nonarterialized mouse liver transplantation is a well-established model for immunologic studies on rejection and tolerance mechanisms. However, the importance of graft arterialization has—in contrast to rat liver transplantation—not been thoroughly examined in the mouse model. The aim of the current study was to investigate the impact of arterial reconstruction on long-term graft survival, histologic alterations, ischemic liver damage, and early immunologic activation pathways.Methods and Results.All recipients of arterialized (n=6) and nonarterialized (n=8) syngeneic liver grafts survived indefinitely. There were no differences in their histologic architecture, including no evidence of bile duct proliferation, periductal fibrosis, or alterations in serum transaminases, in long-term survivors from either group. Twenty-four hours after syngeneic liver transplantation, aspartate aminotransferase and alanine aminotransferase levels were increased to an equivalent extent in both groups, in agreement with early reperfusion injury and solitary traumatic injuries as assessed histologically (n=3 per group). Visualized by immunohistochemistry, intercellular adhesion molecule-1 expression was increased on sinusoidal and hepatic vein endothelium at both 1 and 100 days after transplantation, in both arterialized and nonarterialized grafts. Messenger RNA for interleukin-1, interferon-&ggr;, and tumor necrosis factor-&agr; were measured by real-time polymerase chain reaction 24 hr after transplantation. No significant changes in the expression of cytokine mRNA levels were observed.Conclusions.Arterialization of mouse liver grafts does not appear to have a major impact on survival rate or the degree of immunologic activation. Therefore, the value of arterial reconstruction in mouse liver transplantation for experimental investigations is negligible.

ISSN:0041-1337    

出版商:OVID    

年代:2003

数据来源: OVID