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Biomedical subjects

P Dyer

Publications and source records attributed to P Dyer.

At least 19 recordsLinked to original sources

Effect of cold ischemic time and HLA matching in kidneys coming from "young" and "old" donors: do not leave for tomorrow what you can do tonight.

BACKGROUND: Kidneys from older donors are likely to have a lower nephron mass. Nevertheless they constitute a valuable source of kidney allografts. Long cold ischemic time (CIT), with or without delayed graft function (DGF), has been associated with reduced graft survival. The aim of this study was to review the experience of a single UK center to assess the interaction of cold storage time, donor age, organ exchange, and HLA-DR mismatching on short- and long-term survival. METHODS: We analyzed 788 first cadaver kidney transplants that were performed in our center from 1990 to 1997 and had complete data available. A donor age of 55 years was the cutoff age for "old" and "young" donor kidneys. The primary outcome measured was graft failure from any cause. RESULTS: There were 132 grafts from donors 55 years or older (16.7%), with 76.8% of the kidneys implanted after >20 hr of CIT. Kidney grafts from donors older than 55 years had worse graft survival than grafts from donors younger than 55 (87% vs. 78% at 1 year and 80% vs. 58% at 5 years after transplant, P=0.0001). A CIT of >20 hr significantly reduced graft survival (91% vs.74.3% at 5 years after transplant, P=0.0002) in the young donor group and was associated with an overall graft survival in the old donor group of 57.5% at 5 years. In the same group, ignoring the HLA-DR mismatching to achieve shorter CIT, the predicted initial cost on graft survival at 1 year would have been 3.7% but would have increased to 9% 5 years after transplant. For young donors a CIT of >20 hr had a cost of approximately 18% at 5-year graft survival, far higher than a single DR mismatch. Occurrence of DGF decreased survival in both short (P=0.001) and long (P=0.00001) CIT groups. CONCLUSION: Forming local alliances (common recipient lists) and minimizing delays within the hospital might reduce CIT and DGF while achieving excellent HLA matching. This should improve significantly the outcome of both old and young donor kidney grafts.

Aging↗

Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation.

BACKGROUND: Our group has previously described five different size alleles of an interferon (IFN)-gamma microsatellite. Analyzing this polymorphism, this study correlated high IFN-gamma production with a 12 CA repeat allele (allele 2). Further, our group has described interleukin (IL)-10 polymorphism defining in vitro high and low IL-10 producer status. METHODS: Samples from 88 of 115 consecutive cadaveric renal transplants were used to define polymorphism of both IFN-gamma and IL-10. Patients were separated into high and low genotypes based on the previously reported association between certain genotypes and in vitro production. Graft survival, acute rejection, and serum creatinine at 5 years were analyzed for comparison between groups. RESULTS: The genotype associated with high IFN-gamma production was found in 70 patients. The incidence of acute rejection was 54.3% in the high IFN-gamma genotype group, compared with 44.4% in the low IFN-gamma group. Requirement for antithymocyte globulin therapy was greater in the high IFN-gamma group (odds ratio [OR]=2.5). Among HLA-DR-mismatched patients, IFN-gamma genotype was more strongly associated with rejection (OR=2.86). In the cyclosporine monotherapy subgroup, patients with high IFN-gamma genotype had a 61% incidence of rejection compared with only 20% in the low IFN-gamma genotype patients (OR=3.06). Graft survival was similar between the two groups. When the analysis was controlled for the presence of delayed graft function, 40.5% of the high IFN-gamma genotype patients had serum creatinine levels above 200 micromol/L compared with only 14.3% of the low IFN-gamma genotype recipients at 5 years after transplantation (P=0.05). The high IL-10 genotype was shown to be associated with better graft function at 5 years (75 vs. 50%, P=0.09). CONCLUSION: In this study we have shown that high producer genotype for IFN-gamma may have an influence on acute rejection of kidney transplants, particularly in patients on cyclosporine monotherapy. It is also associated with worse long-term graft function. On the contrary high IL-10 production may have a long-term protective effect.

Acute Disease↗

Clinical response and temporal patterns of acute cellular rejection: relationship to chronic transplant nephropathy.

The association between acute cellular rejection (ACR) and the development of chronic rejection has been the subject of much debate. Studies have suggested that the two phenomena may be linked, or, conversely that there may be no association at all. In order to clarify this relationship the outcome of 284 renal allografts were examined. The transplants were all performed at a single institution between April 1989 and December 1991, allowing a minimum follow up of 5 years. ACR was classified into three clinical response groups: (1) fully responsive to therapy (type 1 ACR), (2) partially responsive (type 2) and (3) ACR requiring treatment with ATG or OKT3 (type 3). Acute and chronic rejection were determined by histological (Banff) criteria. Chronic transplant nephropathy (CTN) occurred significantly more frequently in those with late ACR after day 60 than in those who had early rejection (53.5% versus 17.3%, respectively, P < 0.00001). Acute rejection that was fully responsive to therapy (type 1) had no association with CTN, but partially responsive rejection and rejection requiring second-line treatment were both significantly associated with CTN (P < 0.0001 and P < 0.001, respectively). This study suggests that it is the clinical behaviour and response to treatment of ACR that is paramount in determining the onset of chronic rejection, and not hte mere presence or absence of the clinical phenomenon.

Acute Disease↗

Pre-emptive kidney transplantation: the attractive alternative.

BACKGROUND: Dialysis can be life-saving for patients with end-stage renal failure. However, not only is it associated with significant morbidity and a greater mortality than transplantation, but it is also expensive. Therefore renal transplantation is generally regarded as the treatment of choice for patients in whom this form of renal replacement therapy is appropriate. Transplantation usually takes place after a variable period of dialytic therapy, but pre-emptive kidney transplantation (PKT) has established itself as an attractive alternative. MATERIALS AND METHODS: 1463 consecutive first kidney transplants performed between January 1980 and December 1995 in a single centre were analysed. The 161 patients (11%) transplanted without prior dialysis were compared with the 1302 patients who had been dialysed prior to being transplanted. The pre-emptive group did not differ from the dialysis group in respect of donor age, donor and recipient gender, HLA mismatch, or cold ischaemic time, although there were more live donor transplants within the pre-emptive group. RESULTS: Delayed graft function occurred more frequently in the dialysis group (25% vs 16%) but more patients experienced an acute rejection episode in the pre-emptive group (67 vs 55%). The actuarial graft survival in the pre-emptive group at 1, 5, and 10 years (84, 76 and 67%) was significantly higher than the respective values in the dialysis group (83, 69, and 56%). Within the live donor recipient cohort the survival advantage for the pre-emptive group was even more striking. CONCLUSION: Pre-emptive kidney transplantation not only avoids the risks, cost, and inconvenience of dialysis, but is also associated with better graft survival than transplantation after a period of dialysis, particularly within the live donor cohort.

Adult↗

Transplantation in the elderly.

Studies show that at present fewer patients aged > 60 are on the waiting list for transplantation than would be predicted from their proportion on renal replacement therapy by dialysis. Evidence to date shows that in these older subjects loss of grafts by rejection is less common than it is in younger subjects; there is also absolutely a greater loss of grafts due to death of the patient while the graft still functions. Well-matched grafts should be available to older subjects in whom thorough clinical assessment makes unlikely early death, particularly from cardiovascular causes, following transplantation. If this is to be achieved, agreed approaches to the assessment of such patients and to their inclusion on transplant waiting lists must be established.

Aged↗

Penetrating keratoplasty for pseudophakic corneal oedema.

AIMS: The study was designed to investigate the results of penetrating keratoplasty (PK) for pseudophakic corneal oedema (PCO). METHODS: Retrospective analysis of 80 consecutive patients (82 eyes) who underwent PK for PCO between the years 1980-1992 with a minimum follow up of 12 months. RESULTS: PKs for PCO have accounted for as many as 20% of all grafts performed in the hospital in recent years. The interval between cataract extraction and PK ranged from 6 to 161 months (mean 51 months). The intraocular lens was removed in 45 (55%), left in situ in 30 (37%), and exchanged in seven (8%) of cases respectively. Of the intraocular lenses involved 62% were iris supported, 31% angle supported, and 7% were posterior chamber lenses. Actuarial analysis shows graft survival to be 91% at 1 year and 86% at 2 years after surgery. The likelihood of graft survival was significantly enhanced by removal of the intraocular lens (p < 0.01). A corrected Snellen visual acuity worse than 6/60 was present in 36% of patients with a clear corneal graft. Ocular comfort was achieved in all patients with a clear corneal graft. CONCLUSION: PK for PCO resulted in a disappointing visual result in a large proportion of patients. PK was, however, successful in relieving pain and corneal ulceration when present.

Corneal Edema↗

Increased mortality due to cardiovascular disease in type 1 diabetic patients transplanted for end-stage renal failure.

The graft and patient survivals following renal transplantation in all Type 1 diabetic patients transplanted within the North-West of England between 1981 and 1990 at Manchester Royal Infirmary were studied. Fifty-two Type 1 (insulin-dependent) diabetic patients with end-stage renal failure due to diabetic nephropathy were transplanted during this period. They were compared to controls matched for age, sex, and year of transplantation and also to all 904 patients transplanted during the same period. Graft survival rates at 1 and 5 years in the diabetic patients were lower (80.8% and 62.1%, respectively), compared to controls (88.9% and 77.9%, respectively, p = 0.02) but were similar to those seen in all grafts (80.4% and 59.0%, respectively, p = NS). Actuarial patient survival rate at 5 years was lower in diabetic patients (76.3%) compared to the control group (94.2%, p = 0.003). Myocardial infarction was the main cause (60%) of death in diabetic patients. The results of this large recent series indicate that good graft and patient survival rates can be obtained in Type 1 diabetic patients, although they remain poorer than those of patients with non-diabetic renal disease. More rigorous pretransplantation cardiac assessment and treatment before acceptance of Type 1 diabetic patients for renal transplantation may help to improve patient survival.

Adult↗

Continuous ambulatory peritoneal dialysis and renal transplantation: a ten-year experience in a single center.

OBJECTIVE: To assess whether a renal graft outcome is dependent on the modality of dialysis prior to transplantation and to assess risk of peritonitis and catheter-related problems posttransplantation. DESIGN: Retrospect analysis of the outcome of a first cadaveric renal transplantation from hemodialysis (HD) and CAPD patients over a ten-year period. PATIENTS: Out of a total of 905 renal transplants over a ten-year period, 699 were first grafts; 500 of these (241 on CAPD, 259 on hemodialysis) were analyzed while the remaining (incomplete data, predialysis, pediatric) were assessed for graft and patient survival only. MAIN OUTCOME: Graft and patient survival cases were identical in the two groups (five-year graft survival: CAPD 67%, hemodialysis 66%; five-year patient survival: CAPD 88%, hemodialysis 87%). CAPD posttransplant was necessary in 37 patients, while 10 developed peritonitis mostly related to CAPD use and responded to appropriate therapy. Routine catheter removal posttransplant was undertaken between 8 and 12 weeks. CONCLUSION: Excellent graft and patient survival is achieved independent of the modality of dialysis prior to transplantation. Peritoneal dialysis can be used postgrafting, but there is a risk of peritonitis, which can be successfully managed with antibiotics and catheter removal. Great care is needed in executing the dialysis and catheter care after transplantation.

Adult↗

Characterization of the fluorescence spectra produced by excimer laser irradiation of the cornea.

The epithelium and stroma of bovine and human corneas were exposed to both ablative and subablative levels of 193-nm excimer laser radiation and the spectra of the induced fluorescence recorded. Two broad peaks in the emission spectra were observed, at 310 nm and 460 nm, with a difference in the relative height of these peaks between epithelium and stroma. The lower cut-off for fluorescence (260 nm) was similar for both tissues. Time-resolved measurements showed that fluorescence occurs on the nanosecond time scale, and an estimate gives the quantum yield for photons emitted in the 260-350-nm range as approximately 1 X 10(-5). The significance of these results in the evaluation of the safety of surgery with an argon fluoride excimer laser is discussed.

Animals↗