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Biomedical subjects

M L Nicholson

Publications and source records attributed to M L Nicholson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Human islet cell transplantation--future prospects.

BACKGROUND: Islet transplantation has the potential to cure diabetes mellitus. Nevertheless despite successful reversal of diabetes in many small animal models, the clinical situation has been far more challenging. The aim of this review is to discuss why insulin-independence after islet allotransplantation has been so difficult to achieve. METHODS: A literature review was undertaken using Medline from 1975 to July 2000. Results reported to the International Islet Transplant Registry (ITR) up to December 1998 were also analysed. RESULTS: Up to December 1998, 405 islet allotransplants have been reported the ITR. Of those accurately documented between 1990 and 1998 (n = 267) only 12% have achieved insulin-independence (greater than 7 days). However with refined peri-transplant protocols insulin independence at 1 year can reach 20%. CONCLUSIONS: There are many factors which can explain the failure of achieving insulin-independence after islet allotransplantation. These include the use of diabetogenic immunosuppressive agents to abrogate both islet allo-immunity and auto-immunity, the critical islet mass to achieve insulin-independence and the detrimental effects of transplanting islets in an ectopic site. However recent evidence most notably from the Edmonton group demonstrates that islet allotransplantation still has great potential to become an established treatment option for diabetic patients.

Animals↗
PubMed2001

Rapamycin in transplantation: a review of the evidence.

Rapamycin in transplantation: A review of the evidence. The calcineurin inhibitors have been the mainstays of immunosuppression for solid organ transplantation over the last two decades, but nephrotoxicity limits their therapeutic benefit. Rapamycin is a new drug with both immunosuppressant and antiproliferative properties that has a unique mechanism of action distinct from that of the calcineurin inhibitors. It has a role as a maintenance immunosuppressant either alone or in combination with a calcineurin inhibitor and can also be used to treat refractory acute rejection. Theoretical evidence suggests that it may limit the development and progression of chronic rejection in transplant recipients, but this has yet to be confirmed. This review examines the current in vitro animal and human work underlying the use of rapamycin and, in addition, comments on the pharmacokinetics and side-effect profile of this promising new agent.

Animals↗
PubMed2001

Cytokines and inflammatory pathways in the pathogenesis of multiple organ failure following abdominal aortic aneurysm repair.

Multiple organ failure is a common mode of death following abdominal aortic aneurysm repair, particularly after rupture. Cytokines are the principal mediators of the inflammatory response to injury and high levels of circulating cytokines have been associated with poor outcome in major trauma and sepsis. Abdominal aortic aneurysm repair results in an ischaemia-reperfusion injury to the tissues distal to the site of aortic clamping. The inflammatory response in these tissues causes the release of cytokines, principally Interleukins 1-beta, 6, and 8, and Tumour Necrosis Factor alpha. If released in large enough concentrations, these cytokines may enter the circulation and gain access to organs distant to the site of initial injury. Circulating cytokines cause dysfunction of the renal, cardiovascular, respiratory, nervous and musculo-skeletal systems. The combination of these individual changes in organ function is the multiple-organ dysfunction syndrome, which may progress to multiple organ failure.

Aortic Aneurysm, Abdominal↗
PubMed2001

Use of non-heart-beating donors in renal transplantation.

The rate of renal transplantation has plateaued and is now limited by the number of donor organs available. In the past all donor kidneys came from living donors or controlled non-heart beating donors. It was not until the introduction of brainstem death criteria that cadaveric heart beating donors became the main source. Recently, there has been renewed interest in non-heart beating donors, who have already suffered cardiorespiratory arrest. Kidneys from these donors have a unique set of problems associated with increased duration of warm ischaemia. To minimise this, the kidneys are cooled in situ using an intra-aortic balloon catheter and are perfused with cold hyperosmolar citrate. Retrieval can then proceed in the normal fashion. Despite a higher level of delayed graft function, the results from non-heart beating renal transplantation are good, with long term function comparable to cadaveric organs. If used safely, they enable significant expansion of the donor pool. Techniques in the future, such as machine perfusion preservation, may further improve the results from non-heart beating programmes.

Cadaver↗
PubMed2000

Sub-clinical acute rejection detected using protocol biopsies in patients with delayed graft function.

Acute rejection in renal transplants is difficult to diagnose when patients have delayed graft function (DGF) in the early post-transplant period. In this study protocol, renal transplant biopsies were performed in an attempt to detect sub-clinical acute rejection episodes. Eighty-three patients were eligible for the study, of whom 33 had DGE All had protocol renal transplant biopsies performed under ultrasound control at 7 days post-transplant, and those with DGF had further biopsies weekly until the graft functioned. All histologically confirmed acute rejection episodes were treated. Sub-clinical acute rejection was detected in 6/33 (18%) patients with DGF compared to 2/50 (4%) in the other patients (P < 0.05). Borderline rejection was present in 4/33 (12%) and 4/50 (8%) patients, respectively. Because of the high detection rate of sub-clinical acute rejection and the low morbidity of renal transplant biopsies, their use is recommended in patients with DGF.

Acute Disease↗