Organ transplantation--then and now. (1/498)

The last 25 years have seen amazing progress in transplantation--from the development of techniques for immunosuppression to methods for organ removal and preservation. Our distinguished authors focus on these developments and discuss how the momentum seen during the last quarter century can be accelerated.  (+info)

Transplant surgeons in training: is anybody out there? (2/498)

There is a long-standing recognition that there is an organ donor shortage in the United Kingdom and Ireland (UK&E) that limits transplant activity. However, the fact that, at present, there are several unfilled consultant vacancies would suggest that a shortage of trained surgeons may soon be an equally important limiting factor. The aim of this current study was to identify all transplant trainees in the UK&E and to determine their career aspirations. A list of all trainees intending to practice as transplant surgeons was compiled. A combination of postal questionnaire and telephone interview was used to construct a database on past and present training in transplantation, and preferred type of consultancy was assessed both by direct questioning and by using a visual analogue scale to grade desirability of various posts. Of 110 potential trainees identified, 50 (45%) replied and indicated a desire to pursue a career in transplant surgery. Thirty-one intended practising in the UK&E (19 UK&E graduates and 12 overseas). The preferred consultancy (27/31) was transplantation (Tx) together with a second specialty while only four wanted a multivisceral practice. The mean score (0-10) for desirability of a multivisceral transplant post was 4.7, for renal transplant and vascular access it was 3.6 and for transplantation and a second specialty it was 8.4. We conclude that the majority of trainees do not wish to apply for pure transplant posts, either single organ or multivisceral, and that the majority wish to practice transplantation with a second specialty. In addition, there is still a major shortage of trainees and further studies are required to identify reasons why trainees fail to pursue a career in transplantation.  (+info)

Gene targeting: applications in transplantation research. (3/498)

Gene targeting, the manipulation of gene in the mouse genome using homologous recombination in embryonic stem cells, is a powerful experimental tool that has been widely utilized in a number of disciplines. The ability to precisely alter genes in this way provides an avenue for investigating the role of a gene product in normal and pathological processes in the intact animal, with a precision and efficacy not possible using pharmacological agents, antibodies or engineered proteins. In transplant research, gene targeting provides a unique tool for discriminating the contributions of gene expression in donor versus recipient tissues. This review focuses on several areas in transplantation research where gene targeting has made useful contributions. These include studies of the role of donor and recipient multiple histocompatibility complex antigens in regulating rejection responses, the role of CD4+ T cell in mediating acute rejection, and the functions of cytokines during rejection and tolerance induction. These studies highlight the unique advantages of gene targeting in studies of complex processes in whole animals and illustrate the contributions of this technique to understanding the pathogenesis of allograft rejection.  (+info)

Gene therapy in transplantation in the year 2000: moving towards clinical applications? (4/498)

Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been obtained in small animal experimental models with inhibitors of co-stimulatory signals on T cells, immunosuppressive cytokines, donor major histocompatibility antigens and regulators of cell apoptosis or oxidative stress. The application of gene therapy techniques to transplantation offers a great experimental and therapeutic potential. Local production of immunosuppressive molecules may increase their therapeutic efficiency and reduce their systemic effects. When compared with other clinical situations, gene therapy in transplantation offers several potential advantages. Gene transfer into the graft can be performed ex vivo, during the transit between the donor and the recipient, thus avoiding many of the hurdles encountered with in vivo gene transfer. Furthermore, the difficulties associated with immune responses to the gene transfer vectors and transient gene expression may be easier to overcome when gene therapy protocols are applied to transplantation than when applied to other clinical situations. The next century should witness a rapid increase in the application of gene therapy techniques to large animal pre-clinical models of transplantation and later to clinical trials. Gene Therapy (2000) 7, 14-19.  (+info)

The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. (5/498)

Whereas the standard immunosuppressive agents foster development of posttransplant lymphoproliferative disorders (PTLDs), the impact of RAD, a macrolide with potent immunosuppressive properties, and other immunosuppressive macrolides on these disorders remains undetermined. We found that RAD had a profound inhibitory effect on in vitro growth of six different PTLD-like Epstein-Barr virus+ lymphoblastoid B cell lines. Similar to normal T cells, RAD blocked cell-cycle progression in PTLD-like B cells in the early (G(0)/G(1)) phase. Furthermore, RAD increased the apoptotic rate in such cells. The drug also had a profound inhibitory effect on the growth of PTLD-like Epstein-Barr virus+ B cells xenotransplanted s.c. into SCID mice. The degree of the RAD effect varied among the three B cell lines tested and was proportional to its effects on the cell lines in vitro. In this in vivo xenotransplant model, RAD markedly delayed growth or induced regression of the established tumors. In one line, it was able to eradicate the tumor in four of eight mice. When RAD treatment was initiated before tumor cell injection, a marked inhibition of tumor growth was seen in all three lines. In two of them, the drug prevented tumor establishment in approximately 50% of mice (5/11 and 5/8). In summary, RAD is a potent inhibitor of PTLD-like cells in vitro and in vivo. These findings indicate that, in contrast to the standard immunosuppressive agents, macrolides such as RAD may be effective in prevention and treatment of PTLDs.  (+info)

Comparison of quantitative cytomegalovirus (CMV) PCR in plasma and CMV antigenemia assay: clinical utility of the prototype AMPLICOR CMV MONITOR test in transplant recipients. (6/498)

The correlation between the prototype AMPLICOR CMV MONITOR test (Roche Molecular Systems), a quantitative PCR assay, and the cytomegalovirus (CMV) pp65 antigenemia assay was evaluated in transplant recipients. Sequential blood specimens were collected on 29 patients (491 specimens), the leukocyte fraction was tested by CMV antigenemia, and quantitative PCR was performed on plasma specimens. None of the 15 patients (242 specimens) who were antigenemia negative were positive for CMV DNA by PCR, and none of these patients developed active CMV disease. There were 14 antigenemia-positive patients, 8 of whom developed active CMV disease. In all patients, there was a good association between the antigenemia and PCR assays. Ganciclovir-resistant virus was isolated from three patients with active CMV disease. These three patients had persistently elevated levels of antigenemia and CMV DNA by PCR when resistance to ganciclovir developed. This standardized, quantitative CMV PCR assay on plasma has clinical utility for the diagnosis of active disease and in monitoring the response to antiviral therapy in transplant recipients.  (+info)

Transcatheter implantation of a bovine valve in pulmonary position: a lamb study. (7/498)

BACKGROUND: Pulmonary regurgitation can lead to severe right ventricular dysfunction, which is a delicate postoperative problem in the long-term follow-up of patients who had surgery for congenital heart diseases. Clinical conditions of patients suffering from pulmonary valve incompetence are improved by valve replacement with a prosthetic valve. To date, the surgical approach is the only option to replace a pulmonary valve. We report the first experience of percutaneous pulmonary valve implantation. METHODS AND RESULTS: A fresh bovine jugular vein containing a native valve was sutured into a vascular stent and then cross-linked with a 0.6% glutaraldehyde solution for 36 hours. After being hand-crimped onto a balloon catheter, the device was inserted percutaneously according to standard stent-placing techniques. The valved stent was finally deployed in the position of the native pulmonary valve of the lamb. Hemodynamic evaluation was carried out before and 2 months after implantation. Anatomic evaluation was finally performed. Percutaneous pulmonary valve replacement was successful in 5 lambs. No complications were noted. Early and late angiographic and hemodynamic studies confirmed a good position of the stents with a competent valve at the end of the protocol. One stent was slightly stenotic, with macroscopically visible calcifications. CONCLUSIONS: Nonsurgical implantation of pulmonary valves is possible in the lamb. This new technique is similar to standard stent implantation. Thus, it should be feasible in humans, in whom it will lead to a significant reduction of reoperations in patients in need of pulmonary valve replacement.  (+info)

Therapeutic surgery in failures of medical treatment for fungal keratitis. (8/498)

Medical treatment failure necessitated surgery in nine cases of fungal keratitis. Therapeutic surgery eliminated fungal infection in seven cases, and useful vision was retained in five out of six penetrating keratoplasties. In three cases Natamycin (Pimaricin) therapy rendered fungi non-viable, but two were demonstrable by histopathology. These results suggest that antifungal treatment should be applied for as long as possible before therapeutic surgery in order to improve the final visual outcome.  (+info)

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