Transplantation
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Since the landmark studies of Patel and Terasaki in the late 1960s, pretransplant cross-matching has been performed by HLA laboratories on a 24-hr/7-day basis. In fact, regulating agencies such as the American Society for Histocompatibility and Immunogenetics and the United Network for Organ Sharing have mandated prospective crossmatching for selected solid organ transplants. However, two recent publications (Transplantation 1998; 66: 1833; and Transplantation 1998; 66: 1835) have suggested a change to this approach. Specifically, those authors advocate the transplantation of non-sensitized individuals without a final prospective cross-match as a means to reduce cold ischemia time and the incidence of delayed graft function. Such considerations were predicated upon results generated by cytotoxicity-based antibody screening. We and others, however, have reported that a flow cytometric-based assay is a more sensitive method to detect alloantibodies than cytotoxicity. Furthermore, an increasing number of reports document that graft survival is improved among patients whose final flow cytometric crossmatches were negative compared to patients with positive flow cytometric crossmatches. Although we agree that it is reasonable to transplant truly non-sensitized patients without a prospective final crossmatch, our data demonstrate that a large number of patients deemed non-sensitized by cytotoxicity-based antibody assessment are, in fact, sensitized. ⋯ The concept of transplanting non-sensitized patients without a prospective final crossmatch is appealing and, if bona fide, clearly makes sense. However, our data demonstrate that how a patient is deemed non-sensitized is critical. The difference between AHG- and flow cytometric-based PRA testing is significant and can result in transplantation of alloimmunized patients considered to be non-sensitized. Therefore, we recommend that, if a transplant center chooses to forego a prospective final crossmatch, the decision to do so should be based on methods more sensitive than AHG-CDC.
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CTLA4IgG that binds to B7 effectively inhibits the signaling of CD28/B7 pathway and induces antigen-specific T-cell unresponsiveness in vitro and in vivo. We examined whether the development of obliterative bronchiolitis in a murine heterotopic airway transplantation model is T cell dependent and whether CTLA4IgG abrogates the development of obliterative bronchiolitis. ⋯ We demonstrated that the development of obliterative bronchiolitis in a murine heterotopic airway model involves both CD28/B7-dependent and -independent processes. The luminal obliteration by fibrous tissue is clearly CD28/B7 dependent and can be inhibited by CTLA4IgG. The luminal obliteration of allografted trachea by fibrous tissues and the loss of ciliated columnar respiratory epithelial cells represent distinct disease processes.
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The TT virus (TTV) was discovered in patients with symptomatic posttransfusion hepatitis, but many viremic individuals are asymptomatic. Inadvertent transfusion-associated transmission must therefore be anticipated. We screened blood donors and heart transplant recipients for TTV infections. ⋯ Although TTV is transfusion-transmissible, the parenteral transmission rate may have been overestimated. Many TTV infections are apparently acquired by nonparenteral routes. Immunoglobulins are safe but pooled plasma is not safe regarding TTV transmission.
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Thrombocytopenia is a frequent and potentially serious complication in liver transplant recipients. The role of endogenous thrombopoietin level in posttransplant thrombocytopenia, has not been fully defined in liver transplant recipients. Additionally, there is accumulating evidence to suggest that platelets play a important role in antimicrobial host defense. ⋯ Persistent thrombocytopenia portended a poor outcome in liver transplant recipients and was not related to low TPO levels. Thrombocytopenia preceded infections and identified a subgroup of liver transplant patients susceptible to early major infections; its precise role in fungal infections warrants validation in larger studies.
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Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City. ⋯ Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.