New surgical techniques and surgical site infections.
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Technologic advances in surgery include a trend toward less invasive procedures, driven by potential benefits to patients and by health-care economics. These less invasive procedures provide infection control personnel opportunities for direct involvement in outcomes measurement. (+info)
Human herpesviruses 6 and 7 in solid organ transplant recipients.
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The impact of cytomegalovirus, a member of the beta-herpesvirus subgroup of the Herpesviridae, on patients who have undergone transplantation cannot be overstated. However, in the last 15 years, 2 additional members of the human beta-herpesvirus family have been discovered: human herpesviruses 6 and 7 (HHV-6 and HHV-7). The impact of HHV-6 and HHV-7 is assessed, as is the well-being of transplant recipients. Also discussed is whether the data on the pathological consequences of infection warrant routine screening for these viruses in solid organ transplant recipients. (+info)
Fungal infections in transplant recipients.
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Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores of both fungi that are "pathogenic" even in the normal host, such as Cryptococus neoformans, and those that are "opportunistic", such as Candida and Aspergillus species, among others. Although these latter species may occasionally form fungal balls or induce allergic phenomena in the normal host, they produce more invasive diseases in immunosuppressed patients. Among these diseases, pseudomembranous aspergillosis has recently been described. The diagnostic approach to these entities, and, in particular, the thin dividing line between colonization and infection are addressed, along with the diagnostic value of the various procedures. New prophylactic regimens are reviewed such as the possibility of using amphotericin aerosols in combination with systemic azole administration. The authors would emphasize the importance of restoring lung defences by not only decreasing immunosuppressive regimens but also considering the use of newly available recombinant cytokines such as growth factors, to reduce neutropenia, for instance, in addition to antifungal drugs when infection is diagnosed. However, immunomodulation procedures are far from being well established. (+info)
Molecular genetic basis of porcine histo-blood group AO system.
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Histo-blood group A and B antigens are oligosaccharide antigens important in transfusion and transplantation medicine. The final steps in the synthesis of these antigens are catalyzed by glycosyltransferases encoded by the functional alleles at the ABO locus. Humans have 3 major alleles (A, B, and O), whereas pigs are known to have only A and O alleles. This paper reports the molecular genetic basis of the porcine AO system. The porcine A gene is homologous to the ABO genes in humans and other species. It encodes an alpha1 --> 3 N-acetyl-D-galactosaminyltransferase that synthesizes A antigens. Southern hybridization experiments using a porcine A gene coding-sequence probe failed to identify a corresponding homologous sequence in genomic DNA from group O pigs, thus suggesting a major deletion in the O gene. Therefore, inadvertent activation of a silent O gene seems unlikely in porcine organs xenotransplanted into humans. (+info)
Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation.
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Total lymphoid irradiation (TLI), originally developed as a non-myeloablative treatment for Hodgkin's disease, has been adapted for the induction of immune tolerance to organ allografts in rodents, dogs and non-human primates. Moreover, pretransplantation TLI has been used in prospective studies to demonstrate the feasibility of the induction of tolerance to cadaveric kidney allografts in humans. Two types of tolerance, chimeric and non-chimeric, develop after TLI treatment of hosts depending on whether donor bone marrow cells are transplanted along with the organ allograft. An advantageous feature of TLI for combined marrow and organ transplantation is the protection against graft-versus-host disease (GVHD) and facilitation of chimerism afforded by the predominance of CD4+ NK1.1(+) -like T cells in the irradiated host lymphoid tissues. Recently, a completely post-transplantation TLI regimen has been developed resulting in stable mixed chimerism and tolerance that is enhanced by a brief course of cyclosporine. The post-transplantation protocol is suitable for clinical cadaveric kidney transplantation. This review summarizes the evolution of TLI protocols for eventual application to human clinical transplantation and discusses the mechanisms involved in the induction of mixed chimerism and protection from GVHD. (+info)
The future of organ transplantation: from the laboratory to the clinic.
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This is a short review of tolerance from the point of view of the clinician. Various examples of tolerance occurring in patients and animal models that relate to the clinical experience are described. It is suggested that there may be different mechanisms by which tolerance is achieved, but from the patient's point of view operational tolerance is the goal, whereby, after a short induction procedure, the patient will maintain good function in the grafted organ indefinitely without maintenance immunosuppression. It is pointed out that such a goal may be difficult to achieve with any given protocol due to the enormous variation between donors and recipients of organ grafts of tissue matching, innate immune reactivity and susceptibility to disturbance of a tolerant state by infections or allergic reactions. Thus the case is made for prope or almost tolerance in which graft acceptance is maintained by a low, non-toxic dosage of maintenance immunosuppression that may not be required indefinitely. (+info)
The Immune Tolerance Network: tolerance at the crossroads.
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Immune tolerance therapies are designed to reprogramme immune cells in a highly specific fashion in order to eliminate pathogenic responses but preserve normal immune function. A concept that has tantalized immunologists for decades, tolerogenic therapies would replace current lifelong immunosuppressive regimens and their often debilitating side-effects with short-term immunosuppressive regimens and their often debilitating side-effects with short-term, effective cures. Significant advances have been made over the past decade that have provided a more detailed understanding of the molecular events associated with T-cell recognition and activation. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. As a result of these advances, the Immune Tolerance Network (ITN), a group of 70 expert immunologists spanning multiple disciplines, has been created to identify and promote the use of tolerogenic therapies in the clinic. Using a unique interactive approach designed to speed the development of clinical tolerance therapies, the ITN is examining new and innovative therapeutic approaches and bioassays in a range of autoimmune diseases and transplantation settings, as well as asthma and allergies. This work has been funded by the National Institutes of Health (in collaboration with the Juvenile Diabetes Foundation International). (+info)
Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.
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Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus- based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9-143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C. neoformans infection in organ transplant recipients. (+info)