ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.We previously demonstrated that surfactant dilution and inhibition occur immediately after pulmonary artery flushing with hypothermic modified Euro-Collins solution.Consequently, we speculated that increased capillary permeability contributed to these surfactant changes. To test this hypothesis, we evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary capillary filtration coefficient (Kfc), and additionally performed a biochemical analysis of surfactant.Methods.We used a murine isolated, perfused lung model to measure the pulmonary capillary filtration coefficient and hemodynamic parameters, to determine the wet to dry weight ratio, and to evaluate surfactant by biochemical analysis of lung lavage fluid. We defined three study groups. In group I (controls), we harvested lungs without hypothermic pulmonary artery flushing, and measured Kfcimmediately. In group II (in situ flush), we harvested lungs after hypothermic pulmonary artery flushing with modified Euro-Collins solution, and then measured Kfc. Experiments in groups I and II were designed to evaluate persistent changes in Kfcafter pulmonary artery flushing. In group III (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfcduring hypothermic pulmonary artery flushing.Results.Groups I and II did not differ significantly in capillary filtration coefficient and hemodynamics. Group II showed significant alterations on biochemical surfactant analysis and a significant increase in wet-to-dry weight ratio, when compared with group I. In group III, we observed a significant transient increase in capillary filtration coefficient during pulmonary artery flushing.Conclusions.Hypothermic pulmonary artery flushing transiently increases the capillary filtration coefficient, leads to an increase in the wet to dry weight ratio, and induces biochemical surfactant changes. These findings could be explained by the effects of hypothermic modified Euro-Collins solution on pulmonary capillary permeability.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Idiopathic pneumonia syndrome (IPS) is a frequent and potentially fatal complication of bone marrow transplantation (BMT). We have previously shown that experimental IPS is associated with increased levels of lipopolysaccaride (LPS) and tumor necrosis factor-&agr; (TNF&agr;) in the bronchoalveolar lavage (BAL) fluid, and that administration of LPS to animals with extensive graft versus host exacerbated underlying lung injury (Blood 1996; 88: 3230).Methods.Lethally irradiated CBA mice received BMT from allogeneic (B10.BR) or syngeneic (CBA) donors. The role of TNF&agr; in the exacerbation of pulmonary toxicity caused by LPS injection and in the evolution of IPS after allogeneic BMT was examined by neutralizing TNF&agr; after BMT using a soluble binding protein (rhTNFR:Fc).Results.Five weeks after BMT, administration of rhTNFR:Fc dramatically reduced mortality and prevented the exacerbation of lung injury caused by LPS administration. This protective effect was associated with preservation of pulmonary function and with marked reductions of cells, neutrophils, and LPS in the BAL fluid of treated animals. TNF&agr; neutralization from week 4 to 6 after allogeneic BMT effectively halted the progression of systemic GVHD and significantly reduced, but did not prevent lung injury that developed during the treatment period.Conclusions.We conclude that TNF&agr; is central to early LPS induced toxicity in this model and is a significant, but not the exclusive contributor to the development of IPS after allogeneic BMT.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Transplanted islets lack endothelial cells immediately after implantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly formed islet graft microvessels are largely unknown. This study aimed to investigate the blood flow regulation of transplanted pancreatic islets.Methods.Pancreatic islets were syngeneically transplanted beneath the renal capsule of control and streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks later using laser-Doppler flowmetry. Adenosine (0.6 mg×kg\-1×min\-1), angiotensin II (AT II; 0.17 &mgr;g×kg\-1×min\-1) and the nitric oxide synthase inhibitor NG-nitro-l-arginine (25 mg/kg) were given to each animal.Results.An increased basal blood flow and basal vascular conductance in the islet grafts, but not in the renal cortex, were seen in diabetic rats compared with control rats. Adenosine increased, and AT II decreased, the vascular conductance of the islet grafts in both nondiabetic and diabetic animals. A more pronounced circulatory response to AT II was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft blood flow response between nondiabetic and diabetic animals. NG-Nitro-l-arginine decreased islet graft blood flow and vascular conductance in both nondiabetic and diabetic recipients, but the effect was more pronounced in the nondiabetic animals.Conclusions.Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were less dependent on nitric oxide to maintain a basal blood flow in the islet graft.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.A successful kidney transplant from a living-related donor (LRD) remains the most effective renal replacement therapy for children with end-stage renal failure. The use of LRD kidneys results in decreased time on dialysis, increased graft survival, and better function compared with kidneys transplanted from cadaver donors. We retrospectively analyzed data from the United Network of Organ Sharing (UNOS) Scientific Renal Transplant Registry to determine risk factors for graft loss in children who received an LRD kidney.Methods.Data was obtained from the UNOS Scientific Renal Transplant Registry on 2418 children ranging in age from 0 to 18 years who underwent an LRD kidney transplantation between January 1988 and December 1994. Multivariate analysis of graft survival was performed using Kaplan-Meier and Cox regression models.Results.The effects of age, pretransplantation dialysis, early rejection, and race were found to significantly affect graft survival. Gender, peak panel-reactive antibody, and ABO blood type were not found to be significant risk factors. Infants <2 years of age initially had the worst graft survival; however, over time their results stabilized, and at 7 years estimated graft survival was good (71%). Adolescents ranging in age from 13–18 years had the best initial graft survival, but as time went on graft survival worsened (55%). Patients who underwent pretransplantation dialysis had a relative risk for graft loss of 1.77 (P<0.001), whereas those who had an early rejection had a relative risk for graft loss of 1.41 (P<0.002). African-Americans had a significantly higher relative risk for graft loss than either Caucasians (1.57,P<0.0005) or Hispanics (2.01,P<0.0003).Conclusions.Predictors of graft survival for children who receive LRD kidney transplants include age at transplantation, pretransplantation dialysis, early rejection, and race. Over time, adolescents and African-Americans seem to have the lowest graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.End-stage liver disease for which no cause can be identified, cryptogenic cirrhosis, is a common indication for liver transplantation.Allograft inflammation and fibrosis have been reported to recur with similar frequencies after liver transplantation for cryptogenic cirrhosis and hepatitis C (HCV).Methods.We determined sequential posttransplant allograft histology in four groups of recipients: 31 transplanted for cryptogenic cirrhosis, 70 for cholestatic etiologies, 40 for alcoholic liver disease, and 56 for HCV. Modified hepatitis activity index (HAI) and fibrosis stage were determined at 4 months, 1 year, and at most recent biopsy posttransplantation.Results.The prevalence of HAI≥2 among cryptogenic recipients was similar to that of cholestatic and alcoholic recipients at 4 months, 1 year, and at most recent evaluation (mean 45±17 months posttransplantation). For HCV-infected recipients, the frequency of HAI≥2 was more than for cryptogenic recipients at 1 year (52 vs. 29%,P=0.04) and at most recent evaluation (64 vs. 15%,P=0.003). Fibrosis scores for cryptogenic, cholestatic, and alcoholic recipients were similar at all timepoints. The proportion of HCV-infected recipients with fibrosis stage >2 was more than that of cryptogenic recipients at 4 months (29 vs. 12%,P=0.05), 1 years (46 vs. 7%,P=0.0002), and at most recent evaluation (42 vs. 15%,P=0.06). None of the cryptogenic recipients developed cirrhosis.Results.The frequency of elevated HAI and fibrosis stage in recipients who undergo transplantation for cryptogenic cirrhosis is similar to that of recipients who undergo transplantation for cholestatic etiologies and significantly less than that of HCV-infected recipients. Fibrosis stage and HAI are generally stable after transplantation for cryptogenic cirrhosis. These data do not suggest a viral etiology of liver disease in the majority of patients with cryptogenic cirrhosis.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Chronic rejection is the leading cause of graft failure.Both nonimmunological and immunological mechanisms contribute to this pathology.Methods.We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, serum HLA class &Igr; antigens, cytotoxic antibodies, and lymphocyte population before and after 6 months of follow-up in 22 pediatric renal transplanted patients. The immunosuppressive protocol used was: cyclosporine, azathioprine, and corticosteroids. Eight patients demonstrated chronic graft rejection (by biopsy), group &Igr;; and eight patients had no clinical evidence of chronic and/or acute rejection, group &Igr;&Igr;. Substitution of mycophenolate mofetil (MMF) (600 mg/m2bid for azathioprine was done in patients of groups &Igr; and &Igr;&Igr;. Another six patients with chronic rejection, did not receive MMF, group &Igr;&Igr;&Igr;.Results.Creatinine clearance increased in group &Igr; (44±5 vs. 51.1±6 ml/min/1.73 m2,P<0.03) but it decreased in group &Igr;&Igr;&Igr; (30±3 vs. 25±2,P<0.01). Urinary protein excretion decreased only in group &Igr; (0.3±0.03 to 0.06±0.03 g/24 hr,P<0.03). During MMF therapy antidonor mixed lymphocyte culture decreased 62 and 70% (P<0.05) in group &Igr; and &Igr;&Igr;. Cell-mediated lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group &Igr;. Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group &Igr;&Igr;. Serum HLA class &Igr; antigens, only decreased from 0.7±0.1 to 0.5±0.1 &mgr;l/ml,P<0.05, in group &Igr;. CD19+decreased from 7.9±1.1 to 5.6±0.8%,P<0.05, and 7.8±1.2 to 5.5±0.9%,P<0.05, in groups &Igr; and &Igr;&Igr;, respectively. CD16+increased from 5.7±1.1 to 8.6±1.3 (P<0.05) only in group &Igr;.Conclusions.Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID