ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Despite the longstanding and widespread clinical use of polyclonal antibodies for induction therapy, their immunosuppressive activity has recently further been unraveled. New mechanisms have been identified on depleting and nondepleting effects and new assays have become available for precise assessment of the kinetics of specific antibodies and lymphocyte subsetsin vivo. They allow a better understanding of the delicate balance between over- (infections and malignancies) and under- (acute rejection) immunosuppression using polyclonal antibody induction. In the era of potent new immunosuppressive drugs, polyclonal antibodies are still effective as prophylaxis against rejection and seem to induce an improved long-term allograft survival; however, there is a lack of large prospective, controlled, randomized comparisons of polyclonal antibody induction with standard regimens of conventional and newer immunosuppressive therapy. Variations in patient inclusion criteria, different immunosuppressive protocols and concomitant therapies in different centers, and variation in follow-up periods make it difficult to evaluate the impact of polyclonal antibody induction therapy on long-term graft and patient survival.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The anti-CD3 monoclonal antibody OKT3 has been used as induction therapy in renal transplantation for more than a decade. As compared with patients receiving cyclosporine (Sandimmune, Novartis Pharma, Basel, Switzerland) and azathioprine, patients receiving OKT3 had a lower incidence of rejection and improved long-term graft survival. The advantage of OKT3 induction for survival was apparent only if induction lasted for at least a week and if the administration of cyclosporine was delayed for several days. Patients at higher immunologic risk showed the greatest improvement in graft survival. OKT3 and antithymocyte globulin induction still helps to reduce rejection rates in patients receiving cyclosporine (Neoral, Novartis Pharm.), tacrolimus, or mycophenolate mofetil. OKT3 is, however, a first-generation monoclonal antibody, which may lead to cytokine release, complement activation, sensitization, and overimmunosuppression. This experience has helped to set the standards for the production of new monoclonal antibodies in transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The balance between counteracting acute rejection and drug-related side effects remains a major clinical issue despite the introduction of effective modern chemical immunosuppressive drugs, such as tacrolimus, mycophenolate mofetil, and sirolimus. Tacrolimus is used as a primary drug, whereas mycophenolate mofetil works best as an adjunctive drug to either cyclosporine or tacrolimus, and the role of sirolimus as a primary or secondary drug has yet to be fully determined. All three agents have in several studies demonstrated their ability to reduce the incidence of acute rejection, but none has improved the survival rates. Importantly, the new chemical immunosuppressants are associated with significant drug-specific side effects. These side effects are dose related and they are therefore most often observed during the early postoperative period when patients are given high doses of immunosuppression. Future protocols, combining new genetically modified biologic agents and chemical immunosuppressants, may permit the use of lower doses of the latter, resulting in fewer side effects while still maintaining a low incidence of rejection. In addition, the use of biologic reactants may help to induce transplantation tolerance by targeting individual molecules by interefering with specific signals that are sent to immunocompetent cells. We conclude that chemical immunosuppressants such as tacrolimus, mycophenolate mofetil, and sirolimus do not eliminate the need for antibody induction by biologic reagents in the prophylaxis of renal transplant rejection.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Progress in transplant immunosuppression has occurred in the recent years with the emergence of new immunosuppressive agents as well as new monoclonal antibodies directed against various targets. In this review, we will describe recent works concerning these new monoclonal antibodies (mAb) that have been already used in clinical trials, or are still only in the research field: anti-Il-2 receptor, anti-CD45, anti-CD2 and anti-CD3 mAb that are directed against T cells, and new agents aimed to block the costimulation pathway of the T cell activation, CTLA4-Ig, anti-B7, and anti-CD40 ligand mAb. Promising results in animal models are yet emerging with the achievement of donor specific tolerance, that remains the ultimate goal in human transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Small bowel transplantation results have improved dramatically due to better immunosuppression and management of transplant-related complications. The procedure is technically challenging, and here we review the surgical modifications that have contributed to that success, including a description of the various donor and recipient operations. A new technique for the combined liver–small bowel transplant is described in detail.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The small intestine differs from other transplanted organs by its heavy septic content and its association with a specialized lymphoid system able to target immune responses into the intestinal mucosa. This review focuses on the immunologic singularities of the intestine, describes the immunologic features of intestinal rejection, and analyzes the immunologic strategies currently developed in experimental models to improve tolerance to intestinal grafts, with emphasis on liver-induced tolerance and targeting of receptors involved in T-cell activation.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Advances in immunosuppressive treatment, especially the advent of FK506 (tacrolimus), as well as better monitoring and control of acute rejection have made intestinal transplantation an alternative to definitive parenteral nutrition in patients with permanent intestinal failure. This short review focuses on current clinical results of intestinal transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Intestinal transplantation is an alternative to parenteral nutrition in patients with definitive intestinal failure. The complex clinical and immunologic course of these patients is reflected in a high complication rate as well as patient and graft loss. This review focuses on the pathology of intestinal transplantation. Despite potent immunosuppressive therapy with tacrolimus (FK506), acute graft rejection is still the main complication. In order to institute antirejection treatment as rapidly as possible, a standardized monitoring of histologic rejection is required to diagnose allograft rejection and to differentiate acute rejection from infectious disease, as the two diseases require opposite therapy and are sometimes difficult to differentiate.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID