摘要:

Background.Although much is known about the mucosal damage that occurs after intestinal warm ischemia and reperfusion and its recovery, little is known about the effect of cold preservation and transplantation on the mucosa. We studied the electrophysiological, biochemical, and histological changes of the intestinal mucosa after preservation for 24 hr and subsequent transplantation.Methods.The small intestines from adult mongrel dogs were harvested. The intestines were orthotopically autotransplanted immediately (control group) or after preservation for 24 hr (preservation group). Jejunal and ileal tissues were taken before harvesting, at the end of preservation, 1 hr after reperfusion, and on postoperative days 3, 7, 14, and 28. The Ussing chamber method was used to study the electrophysiologic changes. Tissue maltase, diamine oxidase, and ornithine decarboxylase were measured. A histological analysis was also performed.Results.Control group grafts showed no evident deterioration in electrophysiology, biochemistry, or morphology. In contrast, preservation group grafts exhibited electrophysiological and biochemical degradation, complete denudation of the villi, and crypt injury (especially in the ileum) after reperfusion. Electrophysiologic function and the mucosa biochemical marker recovered within 3 days in the jejunum and within 7–14 days in the ileum; however, histological recovery of mucosal injury required 28 days in the jejunum and more than 28 days in the ileum.Conclusions.Our study showed that despite severe destruction of mucosal integrity by prolonged preservation and transplantation, the intestinal mucosa has an enormous regenerative capacity. Our study also showed that regeneration was more pronounced in the jejunum than in the ileum.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngeneic pancreas grafts were reinnervated in rats.Methods.Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duodenum were removed 4 or 40 weeks after implantation, and processed for indirect immunofluorescence using antibodies directed against vasoactive intestinal peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5.Results.Four weeks after transplantation a moderate to rich number of protein gene product 9.5-positive nerve fibers were found homogeneously distributed through the pancreas, probably representing the intrapancreatic nervous system, because the grafted pancreas lacked both a sympathetic (TH/NPY) and sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of the animals there was a marked increase in SP-immunoreactive nerves (lacking CGRP), most conspicuous in the duodenal portion, both 4 and 40 weeks after transplantation probably secondary to a chronic pancreatitis. The fibers seemed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive intestinal peptide-containing nerve fibers probably also emanating from local ganglia could be seen throughout the grafted pancreas both 4 and 40 weeks after transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerve fibers were still virtually lacking in the pancreas. To trace the origin of the ingrowing nerve fibers, the tracer True Blue was injected into the grafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the celiac ganglion (presumably sympathetic nerves) and few in dorsal root ganglia (sensory nerves).Conclusions.The data suggest that the transplanted rat pancreas becomes reinnervated by mainly sympathetic nerve fibers.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure.This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts.Methods.Recipient animals were either rats with d-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers.Results.Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after d-galactosamine injection. Elevated tumor necrosis factor-&agr; and interleukin-1&bgr; levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts.Conclusion.These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.The potential benefits of islet xenografting in type 1 diabetes include the intriguing, but still unanswered, possibility that the grafted xeno-islets may be less subjected to human autoimmune attack. Cytokines may play a major role in the pathogenesis of autoimmune diabetes by causing impairment of insulin release and pancreatic islet cell toxicity.Methods.We compared insulin secretion, islet cell death and survival, inducible nitric oxide synthase (iNOS) mRNA expression, nitrite production, and Bcl-2 and Bax mRNA expression in isolated human and large mammal (bovine) islets exposed to 50 U/ml recombinant human interleukin-1, 1000 U/ml recombinant human tumor necrosis factor-&agr; and 1000 U/ml recombinant human interferon-&ggr;.Results.After 24-hr exposure, a marked decrease of glucose-stimulated insulin secretion was observed with human, but not with bovine islets. After 48-hr exposure, human, but not bovine, pancreatic islets showed a significantly higher percentage of apoptotic cells compared to controls. Treatment of human islets with human cytokines induced up-regulation of iNOS mRNA, increased levels of nitrites, and down-regulation of Bcl-2 mRNA, with unchanged levels of Bax mRNA. These parameters were not affected by cytokines in bovine islets.Conclusions.Bovine islets are less susceptible than human islets to the effects of human cytokines, which may be a potential advantage of xenotransplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Acute rejection is a common problem in heart transplantation and may contribute to the development of cardiac allograft vasculopathy.This study was designed to evaluate the mechanisms of coronary endothelial dysfunction associated with ischemia-reperfusion and acute untreated rejection.Methods.Two groups of mongrel dogs (n=7 per group) underwent heterotopic cervical heart transplantation without immunosuppression. Allografts were harvested on posttransplant day 1 (group 1) and day 5 (group 2). A third group of unoperated dogs served as control (group 3). After harvesting, epicardial coronary arteries were studied in organ chamber for endothelium-dependent and independent reactivity.Results.Group 1 displayed multifocal ischemic damage without any rejection while hearts from group 2 reached grade IV rejection. Immunohistochemical studies for von Willebrand factor showed expression on coronary endothelial cells in all animals with scattered areas of denudation in transplanted groups. Endothelium-dependent responses to acetylcholine, calcium ionophore A23147, and bradykinin were unaffected in groups 1 and 2. Endothelial relaxations to sodium fluoride (Gi-protein activator) was significantly reduced in group 1 and significantly increased in group 2 compared with control. Responses to serotonin and UK14304 (receptors linked to Gi-protein) were significantly increased in group 2. Responses to thrombin were decreased in both groups. Endothelium-independent responses were unaffected.Conclusions.In the canine model of heterotopic heart transplantation, the early (24 hr) endothelial dysfunction seen after transplantation is specific to the thrombin receptor and the Gi-protein signaling pathway. Acute untreated rejection did not modify the alteration in endothelial reactivity to thrombin but enhanced the sensibility of the Gi-protein signaling pathways.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Given the potential influence of alloantibodies on organ graft outcome, this study investigated the induction of antigraft and antirecipient antibodies after allogeneic and semiallogeneic rat small bowel transplantation.Methods.Fully allogeneic, unidirectional rejection and unidirectional graft-versus-host disease (GvHD) heterotopic small bowel transplantation was performed using DA, PVG, and (PVGxDA)F1donor-recipient combinations. Serum was obtained before and at time points after transplantation and incubated with blood from untransplanted DA and PVG rats. Antibody binding to T cells was detected by whole blood flow cytometry using FITC-conjugated anti-rat IgM murine monoclonal antibody. Antibody levels were determined by reference to a standard curve of fluorescent intensity generated using a serum sample with known anti-target cell IgM activity. Data are presented as arbitrary units/ml (AU/ml).Results.In the PVG→DA combination, five of six DA recipients had detectable anti-graft (PVG) antibodies by day 4 after transplantation (mean 72 AU/ml) and all animals were positive by day 6 (976 AU/ml). Antirecipient (DA) antibodies were also induced, however, they were only apparent after 6 days in five of eight animals (90 AU/ml). Antigraft (DA) antibody responses were also induced in the DA→PVG combination (day 6–218 AU/ml), however no antirecipient (PVG) response was apparent. Transplantation induced antirecipient (DA) antibodies in the unidirectional GvHD model (day 6–90 AU/ml) and an anti-graft (PVG) response in the unidirectional rejection model (day 6–60 AU/ml). However, the latter was quantitatively lower than that generated in the PVG→DA combination (day 6–976 AU/ml).Conclusions.Antigraft and antirecipient antibody responses are simultaneously induced after fully allogeneic small bowel transplantation, despite rejection being the predominant clinical feature. Further studies are required to elucidate their influence on graft outcome.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Necrotic patches and hemorrhagic lesions develop in the renal tissue between day 4 and day 5 after transplantation of fully allogeneicDArat kidneys toLEWrecipients.These lesions are at least in part due to destruction and obstruction of blood vessels. Damage of graft endothelial cells and blood coagulation are likely to be mediated by intravascular graft leukocytes. However, this cell population has not been thoroughly characterized before.Methods.We perfused untreated control kidneys, renal isografts, and allografts on day 4 after transplantation with phosphate-buffered saline/ethylenediaminetetraacetic acid to harvest leukocytes from both the blood stream as well as from the marginal intravascular pool. The mRNA expression of typical products of activated monocytes was analyzed in reverse-transcriptase polymerase chain reaction experiments. Graft monocytes were purified and their immunophenotype was investigated by flow cytometry.Results.Allograft rejection led to a 10-fold increase in the number of intravascular graft leukocytes compared to isografts. A mean number of about 100×106leukocytes was harvested from a single allogeneic kidney, about 73% of these cells were monocytes and most of them displayed an activated phenotype. Compared to isografts, intravascular allograft leukocytes displayed an increased expression of tumor necrosis factor-&agr;, inducible NO synthase and tissue factor.Conclusions.Our study shows that large numbers of activated monocytes accumulate inside allograft vessels. As they express genes the products of which might damage the allograft by inducing cell death or thrombosis, we speculate that they directly participate in allograft destruction.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.The treatment of posttransplant lymphoproliferative disorder (PTLD) remains empirical. We review our treatment of seven cases of PTLD consisting of five interventions: 1) reduction of immunosuppression; 2) antiviral drugs; 3) interferon-&agr;; 4) gamma-globulins; and 5) anti-CD19 monoclonal antibodies.Methods and Results.Seven consecutive patients who had undergone a simultaneous pancreas-kidney, liver, heart, or kidney transplantation were treated. One patient acquired a primary EBV infection with an oligoclonal immunoblastic lymphoma early after pancreas-kidney transplantation; all others developed a monoclonal polymorphic or immunoblastic lymphoma 2 to 123 months after transplantation. In all patients extranodal sites were involved, in three the graft was also involved. Five patients received the full quintuple approach and all rapidly obtained a complete remission (CR) with a median follow-up of 31 months (7-74 months). Of the two patients who did not receive interferon-&agr; for fear of graft rejection one responded slowly with a CR after 7 months, and the other obtained a rapid CR followed by a relapse at 4 months. All three patients with a liver or heart transplant could keep their graft. All patients are still alive with a median follow-up of 31 months (7-74 months).Conclusion.This combined approach resulted in a favorable outcome in patients with high risk monoclonal PTLD after solid organ transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.The aim of this study was to compare the effectiveness of intravenous immunoglobulin (IVIg) versus monoclonal anti-CD3 as a treatment for steroid-resistant rejections. From January 1995 to June 1997, 30 patients were analyzed. They were randomized into two groups. Resistant rejections were diagnosed by core biopsy. Group A received 500 mg/kg/day IVIg (Sandoglobulin) for 7 consecutive days, whereas group B received 5 mg/day of OKT3 for 14 consecutive days. Daily T cell CD3+peripheral count was performed for 14 days for group B. The immunosuppression was similar for both groups. Cyclosporine was stopped during both treatments.Methods.Demographic factors, HLA mismatch, creatinine levels before and after treatment, and the incidence of rejections after treatment (up to 1 month) were taken into account for this study.Results.Data from different samples were compared using Fisher’s exact test. Graft and patient survival were analyzed using the Kaplan-Meier method. The were no significant differences found in age, graft origin, HLA mismatch, or time of follow-up until the episode of rejection. Success was achieved for 11 (73.3%) of 15 of group A and 13 (86.6%) of 15 of group B (P=0.79). Creatinine levels before and after treatment were as follows: A, 2.99±1.30 mg/dl and 2.1±0.70 mg/dl versus B, 3.1±1.1 mg/dl and 2.5±0.8 mg/dl. Besides, we did not observe differences in the creatinine 1 month after treatment (A: 2.35±0.78 mg/dl; B: 2.51±1.10 mg/dl;P=0.66) nor in the third month (A: 1.83±0.58 mg/dl; B: 2.30±0.89 mg/dl;P=0.24). The incidence of rejections after treatment was 5 (46%) of 11 for group A and 9 (75%) of 12 for group B (P=0.4). The patient survival rates 2 years after treatment were 87 and 92% for A and B groups, respectively. Graft survival was identical (80% in both groups).Conclusion.Should the favorable result presented in this report be confirmed in larger number of patients, IVIg could become the preferable choice of rejection treatment for steroid-resistant rejection because of a complete absence of the unwanted side effects commonly associated with OKT3.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Background.Parvovirus B19 (B19) infection is known to cause chronic infection leading to anemia in immunocompromised patients.Although nosocomial B19 infections in immunocompetent patients have been documented, no outbreaks in immunocompromised patients have been previously reported. Whether transmission can occur from a patient with chronic infection is also unknown.Methods.An outbreak of B19 infection in a renal transplant unit was investigated by molecular analysis of the virus strains and a case-control study.Results.Three patients had genetically identical virus strains suggesting the occurrence of nosocomial transmission. The index case transmitted infection many weeks after the onset of her clinical symptoms. Other patients at risk of acquiring infection were those most intensively immunosuppressed. Viral load in the serum correlated with the hematological response. A rebound in the viral load was associated with clinical relapse and the failure of i.v. immunoglobulin therapy.Conclusion.Nosocomial transmission of B19 can occur from immunocompromised patients even when they are in the chronic stage of the infection. The clinical and virological response to i.v. immunoglobulin therapy is variable and depends on the overall level of immunosuppression of the patient.

ISSN:0041-1337    

出版商:OVID    

年代:2001

数据来源: OVID