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

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.Induction of tolerance to organ transplants will increase graft survival and decrease patient mortality and morbidity. Radiation-induced cytoreduction/ablation followed by donor hematopoietic cell reconstitution has been the most consistently successful approach to experimental tolerance induction. However, reluctance of clinicians to expose recipients to radiation has hampered its clinical application.Methods.In the studies described, administration of polyclonal antilymphocyte serum (ALS), donor-specific bone marrow (DSBM) (150×106cells), and sirolimus (24 mg/kg) in a completely mismatched murine model (B10.A donor, C57B/10 recipient) produced 100% indefinite (>250 days) skin graft survival. The level and character of donor-specific chimerism was evaluated with flow cytometry.Results.Specific tolerance was confirmed by continued acceptance of primary and secondary donor-specific skin allografts and rejection of third-party grafts. The level and duration of chimerism induced was directly related to the dose of DSBM administered. Mice given 150×106DSBM cells showed levels of 8-10% donor peripheral blood mononuclear cell chimerism by 30 days, and these levels persisted indefinitely (>250 days) in association with permanent tolerance of donor grafts. Eighty percent of donor chimeric cells were B lymphocytes (MHC class I and II positive, Fc receptor positive, CD45/B220 positive but negative for CD4, CD8 and Thy 1.2) and 20% were sorted in the macrophage monocyte population.Conclusions.These studies demonstrate for the first time that cytoreduction/ablation with ALS combined with sirolimus and reconstitution with donor bone marrow induces tolerance and chimerism in a completely mismatched murine combination. The use of ALS and sirolimus, currently employed therapies in clinical transplantation, and the lack of requirement for radiation make this tolerance protocol attractive for clinical application.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Introduction.A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathio-prine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus.Methods.In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n=40) or CsA (n=38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured.Results.At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11,P=0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often.Discussion.Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Experimentally, the University of Wisconsin solution (UW) has been shown to be superior to the EuroCollins solution (EC) for lung graft preservation. We showed previously that the inclusion of the trisaccharide raffinose as an impermeant in the UW is largely responsible for this superiority. In this study, we used a new porcine model of isolated lung reperfusion to evaluate the use of a simple solution of phosphate-buffered raffinose (PBr) for lung preservation.Methods.Lungs were stored for 24 hr at 4°C after a single pulmonary artery flush with either UW (n=5) or PBr (n=5) solution. Left lungs were ventilated with room air and reperfused for 4 hr by venovenous extracorporeal circulation from a support animal. Controls (n=5) were flushed with UW and reperfused without storage.Results.Control lungs performed better than those stored in either solution in terms of oxygenation (P=0.034) and airway pressure (P=0.032). There were no significant differences between the two stored groups for any parameters. Data for stored lungs after 4 hr of reperfusion (means with 95% confidence intervals) include oxygenation (mm Hg): control 101.6 (14.5), UW 85.2 (14.5), PBr 75.0 (14.5); blood flow (ml/min): control 572 (90), UW 466 (90), PBr 468 (90); peak airway pressure (mm Hg): control 15.9 (3.0), UW 21.0 (3.0), PBr 22.6 (3.0); pulmonary artery pressure (mm Hg): control 17.5 (3.2), UW 22.3 (2.9), PBr 24.5 (2.9). Graft edema (percentage tissue water): control 86.4 (0.8), UW 89.9 (1.8), PBr 89.3 (1.0).Conclusion.PBr is a far simpler and less expensive alternative to UW, and appears to provide a similar level of lung graft protection.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID