ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Graft-versus-host disease (GVHD) remains the most significant obstacle to the use of allogeneic bone marrow transplantation as a treatment for leukemia and other hematological malignancies. Because current GVHD treatment regimens such as cyclosporine and methotrexate are only partially effective, there is a need for new immunosuppressive drugs for the treatment of this condition.Methods.A recently developed immunosuppressive drug, mycophenolate mofetil(MM), was tested in a fully mismatched (C57BL/6 donors to BALB/c recipients) murine model of acute GVHD after bone marrow transplantation.Results.A dose regimen of 30 mg/kg/day given by oral gavage and begun at 1 day before transplant had no positive effect on survival and was found to retard the rate of marrow engraftment as measured by absolute blood neutrophil counts. In all subsequent experiments, treatment was begun on day 5 after transplant. Three different doses (30, 60, and 90 mg/kg/day) were tested, but no significant improvement in mean survival time (MST) was observed for the first two doses (P=0.412 and 0.100, respectively). The highest dose (90 mg/kg/day) reduced MST (P=0.059), and no further dose increases were attempted. MM in combination with cyclosporine also failed to improve MST compared with animals treated with cyclosporine alone or controls.Conclusions.These results suggest that MM given orally is not effective in this murine model of GVHD and may not have a role in the treatment and prevention of acute GVHD arising from bone marrow transplantation in the clinical setting.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The pathogenesis of chronic rejection likely involves an interplay between immunogenic and nonimmunogenic factors. The objective of this study was to determine the influence of cold ischemic preservation injury on the rate of progression to chronic rejection in the Lewis to F344 cardiac allograft model.Methods.To induce an ischemic injury, donor hearts were stored for 3 hr at 4°C in University of Wisconsin solution before transplantation. Allografts were excised at 1, 7, and 90 days after transplantation or at rejection. Vasculopathy was graded for degree of intimal thickening based on the involvement of vascular perimeter and luminal compromise.Results.The degree of vessel injury in ischemic injured allografts at 90 days was significantly greater than in nonischemic injured allografts(2.8±0.4 vs. 1.6±0.5,P<0.05). Ischemic injury in syngeneic grafts did not induce a vasculopathy. Immunoperoxidase staining with R73 (anti-T cell) and ED1 (anti-macrophage) monoclonal antibodies revealed that, in ischemic injured allografts at 90 days after transplantation, the infiltrate was composed predominantly of T cells and macrophages. Additionally, ischemic injured allografts excised at 7 days after transplantation showed cellular infiltrates composed of R73-positive T cells and rare interleukin-2 receptor-positive cells, which was not observed in nonischemic allografts or ischemic syngeneic grafts.Conclusions.The progression to chronic vasculopathy in this model is principally an immunologic process, which is accelerated by an ischemic insult to the allograft. The vascular injury is mediated in part by T cells and macrophages.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The expression of Fas ligand (FasL) in the eye has been proposed to be an important component of ocular immune privilege. Since the unusually favorable outcome of corneal transplantation is thought to result from the immune privilege of the eye, examination of the function of FasL on corneal allografts would be a test of that hypothesis.Methods.To investigate the role of Fas-FasL interaction in corneal allografts, orthotopic corneal transplantation was performed using C57BL/6(B6, FasL+) and B6-gld (FasL-) mice as cornea donors and BALB/c mice as recipients. The rejection rate of B6-gld grafts (FasL-group) was compared with that of normal B6 control corneas.Results.The rejection rate at the final observation (8 weeks) in the FasL-group (89%) was significantly higher than in the FasL+control group (47%). FasL expression was found on the corneal endothelium by staining with anti-FasL monoclonal antibodies. The TdT-mediated dUTP nick-end labeling assay revealed that apoptotic cells were attached to the endothelium in the control group but not in the FasL-groups.Conclusions.Apoptosis of infiltrating cells on the corneal endothelium resulting from Fas-FasL interaction plays an important role in the high success rate of corneal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.If the transplantation of immunoisolated porcine islets into human diabetics is to become reality, the development of a long-term storage method represents an important prerequisite. However, information on cryogenic storage of porcine islets is scanty and fragmentary.Methods.Porcine pancreatic islets microencapsulated in alginate-polylysine-alginate membranes were cryopreserved and assessed both in vitro by static glucose challenge and in vivo in a transplantation study. Two separate methods of islet cryopreservation were compared: method A, using the Bio Cool III freezing machine, and method B, which uses the Nalgene isopropyl alcohol insulated cooler.Results.Method A was found to have better preserved the ability of the microencapsulated cryopreserved islets to respond to high-glucose static challenge (7 out of 10 lots) compared with method B (1 out of 10 lots). Upon exposure to high glucose, the islet batches that did retain the ability to respond to glucose were shown to have secreted an average of 1220±73 pM/24 hr/islet of insulin as compared with 1528±118 pM/24 hr/islet for fresh islets. The presence of isobutyl methylxanthine further potentiated insulin secretion to 1805±81 pM/24 hr/islet and to 2410±104 pM/24 hr/islet for cryopreserved and free islets, respectively. Intraperitoneal transplantation of 2000 cryopreserved microencapsulated porcine islets into streptozotocin-diabetic mice resulted in the reversal of hyperglycemia in 6 out of 10 recipients for the duration of the 90-day study.Conclusions.The effective protection of the delicate porcine endocrine tissue during the cryopreservation process and the subsequent long-term storage were demonstrated with considerable success in this study

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.We investigated the influence of humoral injury during xenoperfusion of porcine livers by human blood.Methods.The porcine livers were perfused under physiological conditions for 9 hr. The perfusates consisted of porcine whole blood in group 1, human whole blood in group 2, and human whole blood with soluble complement receptor type 1 (300 μg/ml) in group 3.Results.Liver enzyme release and serum hemoglobin in group 2 increased significantly after 3 hr of xenoperfusion, compared with those in group 1 and group 3 (P<0.05). Severe histological damage with minimal cellular infiltration was observed in group 2 after 6 hr of xenoperfusion, but was present only at trace levels in group 1 and group 3. In group 2, von Willebrand factor, a possible target of natural antibodies, was induced on sinusoidal endothelial cells after 3 hr of xenoperfusion, correlating with diffuse deposition of human IgM and membrane attack complex. In group 3, von Willebrand factor, human IgM, and membrane attack complex staining in the intralobular region were present at trace levels. In group 3, the indocyanine green removal capacity, representing hepatocyte function, was significantly higher than in group 2 (P<0.05).Conclusions.Based on these results, we suggest that humoral injury is a major cause of liver damage during liver xenoperfusion. The pattern of humoral injury in xenoperfused livers may be attributed to anatomical features of the liver and unique responses of sinusoidal endothelial cells to xenoperfusion.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Short- and long-term patient and graft survival rates are better for living donor (vs. cadaver) kidney transplant recipients. However, donor nephrectomy is associated with at least some morbidity and mortality. We have previously estimated the mortality of living donor nephrectomy to be 0.03%. In our present study, to determine associated perioperative morbidity, we reviewed donor nephrectomies performed at our institution from January 1, 1985, to December 31, 1995.Methods.The records of 871 donors were complete and available for review. Of these donors, 380 (44%) were male and 491 (56%) were female. The mean age at the time of donation was 38 years (range: 17-74 years), and mean postoperative stay was 4.9 days (range: 2-14 days).Results.We noted two (0.2%) major complications: femoral nerve compression with resulting weakness, and a retained sponge that required reexploration. We noted 86 minor complications in 69 (8%) donors: 22 (2.4%) suspected wound infections (only 1 wound was opened), 13 (1.5%) pneumothoraces (6 required intervention, 7 resolved spontaneously), 11 (1.3%) unexplained fevers, 8(0.9%) instances of operative blood loss ≥750 ml (not associated with other complications), 8 (0.9%) pneumonias (all of which resolved quickly with antibiotics alone), 5 (0.6%) wound hematomas or seromas (none were opened), 4(0.5%) phlebitic intravenous sites, 3 (0.3%) urinary tract infections, 3(0.3%) readmissions (2 for pain control and 1 for mild confusion that resolved with discontinuation of narcotics), 3 (0.3%) cases of atelectasis, 2 (0.2%) corneal abrasions, 1 (0.1%) subacute epididymitis, 1 (0.1%)Clostridium difficilecolitis, 1 (0.1%) urethral trauma from catheter placement, and 1 (0.1%) enterotomy.At our institution, no donor died or required ventilation or intensive care. We noted no myocardial infarctions, deep wound infections, or reexplorations for bleeding. Analysis, by logistic regression, identified these significant risk factors for perioperative complications: male gender(vs. female,P<0.001), pleural entry (vs. no pleural entry,P<0.004), and weight ≥100 kg (vs. <100 kg,P<0.02). Similar analysis identified these significant risk factors for postoperative stay>5 days: operative duration≥4 hr (vs. <4 hr,P<0.001) and age ≥50 years(vs. <50 years,P<0.001).Conclusions.Living donor nephrectomy can be done with little major morbidity. The risks of nephrectomy must be balanced against the better outcome for recipients of living donor transplants.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The aim of the present analysis was to define the role of simultaneous heart and kidney transplantation (HNTX) using organs from the same donor by evaluation of clinical strategy and achieved outcome compared with a reference group of concurrently single heart transplant (HTX) and kidney transplant (NTX) recipients. Compared with other organ combinations(pancreas-kidney, heart-lung), HNTX has been performed infrequently and is reported mainly as case records in the literature. Because of expansion of recipient selection criteria for HTX and NTX, the number of patients requiring simultaneous replacement of both organs is increasing.Methods.Six HNTX recipients, three of them suffering from long-standing type I diabetes, received transplants between September 1990 and March 1996 and were analyzed in terms of clinical and immunological demographics and outcome. They were compared with 379 HTX and 769 NTX recipients operated upon within this period.Results.Survival for HNTX is 100% with a mean follow-up of 32.7±21.1 months. Cold ischemic time of the kidney was significantly shorter for HNTX than for NTX (6.5±1.0 hr vs. 22.1±6.8 hr,P<0.005). Although HNTX patients received HLA-unmatched grafts, no rejection of the kidney has been observed to date. There was no difference for rejection of the heart in HNTX compared to HTX recipients.Conclusions.Satisfying results are obtained by HNTX and justify the use of two organs for one recipient. The favorable immunological behavior of the kidney despite use of HLA-unmatched grafts is most probably explained by higher immunosuppression and short cold ischemic time, although a combination effect cannot be excluded.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundAt the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined.Methods.To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis.Results.Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides>300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly.Conclusions.Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Human ehrlichiosis, a newly described zoonotic infection, can be classified as human monocytic ehrlichiosis (HME) or human granulocytic ehrlichiosis (HGE). Although the clinical manifestations of HME and HGE are similar, the type of leukocyte infected, the etiologic agent, and the tick vector are distinct.Methods.We report the first case of HGE in a solid organ transplant recipient and review the literature on HGE.Results.Our patient displayed typical epidemiological, clinical, and laboratory features and responded promptly to therapy with doxycycline.Conclusions.Although opportunistic infections are relatively common in the posttransplant population, one must always consider other infections that occur in normal hosts as well. Human ehrlichiosis should be included in the differential diagnosis for transplant patients with fever, cytopenias, and hepatitis, especially if exposure to ticks in endemic areas has occurred.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID