Biomedical subjects
Publications and source records attributed to S Fenton.
Evidence of snowdrop lectin binding to human white cells supports the need for greater understanding of the possible health consequences of incorporating plant lectins into the food chain.
METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.
PURPOSE: To assess the effectiveness of primary posterior capsulorhexis without anterior vitrectomy in preventing posterior capsule opacification (PCO) in pediatric cataract surgery. SETTING: Children's Hospital, Dublin, Republic of Ireland. METHODS: The study comprised 32 eyes of 22 pediatric patients who had cataract extraction between 1994 and 1998. Extracapsular cataract extraction was performed using radiofrequency diathermy capsulorhexis to the anterior and posterior capsules without an anterior vitrectomy. Posterior chamber intraocular lens implantation was performed in 20 eyes. There were 23 congenital, 6 developmental, and 3 traumatic cataracts. RESULTS: Patient age ranged from 1 month to 12 years. Mean follow-up was 19 months (range 6 to 50 months). Twenty-seven of 32 eyes (84.4%) had a clear visual axis at last follow-up. Five eyes required a neodymium: YAG capsulotomy, which was performed a mean of 5 months postoperatively (range 1 to 9 months). The incidence of PCO requiring capsulotomy was 15.6%. CONCLUSION: Primary posterior capsulorhexis without anterior vitrectomy was safe and effective, with a low reopacification rate. Long-term follow-up of this patient cohort is necessary.
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1. The 5-year actuarial graft, patient and functional graft survival rates were analyzed in 743 consecutive primary cadaveric kidney transplants from The Toronto Hospital between January 1985-December 1997. 2. Recipient age > or = 55 years, male recipient sex, recipient diabetes mellitus, CIT > 36 hours and delayed graft function were found to significantly decrease patient survival. 3. Recipient age > or = 55 years, sensitization to HLA antigens (peak PRA > 50%), donor/recipient HLA antigen mismatches, CIT > 36 hours, delayed graft, function and 6-month SCr > 200 mumol/L were found to significantly decrease graft survival. 4. Acute rejection episodes had no significant impact on overall 5-year patient or graft survival. 5. The observation that serum creatinine > 200 mumol/L had a major adverse influence on long-term outcome reflects the importance of functional renal mass on graft survival.
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Thrombotic microangiopathy is an uncommon but well described complication of renal transplantation. This study is a review of the case records of 18 patients with biopsy proven post transplant thrombotic microangiopathy, without cellular rejection. There was no single characteristic underlying cause of renal failure in native kidneys. Although only two (11%) patients had undergone previous transplantation, 16 (89%) had panel reactive antibodies (PRA). All patients received prophylactic antilymphocyte globulin, a single patient had cyclosporin A (CSA) at the time of transplant and in 16 patients CSA was introduced when graft function was established. On this protocol 16 (89%) patients had early graft function. All patients developed acute renal failure and 16 (89%) required dialysis. Nine (50%) patients developed hematological abnormalities. All patients were treated aggressively with anti-rejection therapy, CSA was temporarily withdrawn, and 2 (11%) patients received plasmapheresis. Seven (39%) patients lost their grafts. Renal function in the remaining patients recovered to serum creatinine levels ranging from 104 mumol/l to 430 mumol/l (1.2 mg% to 4.8 mg%). All patients with surviving grafts had CSA successfully reintroduced. This study indicates that there is an association between patients who develop posttransplant thrombotic microangiopathy after CSA administration and high PRA levels. The condition appears to respond to anti-rejection therapy and stopping CSA in the majority of cases. The safe reintroduction of CSA suggests that endothelial cell damage in the posttransplant period may be multifactorial and not solely due to CSA therapy.
Previously, our laboratory has shown that prolactin (PRL) inhibits epidermal growth factor (EGF)-induced DNA synthesis. One pathway for the initiation of DNA synthesis is EGF-receptor (EGF-R) signaling through Ras and mitogen-activated protein kinase (MAPK). To determine the effects of PRL on EGF-induced MAPK activation and phosphorylation, MAPK or phosphotyrosine (Tyr(P)) was immunoprecipitated from normal murine mammary epithelial (NMuMG) cells treated with PRL (100 ng/ml) and/or EGF (10 ng/ml) for 10-min periods. EGF-induced phosphorylation and activation were then examined by Western analysis and a myelin basic protein (MBP)-specific kinase assay. The p42 isoform of MAPK showed a distinct decrease in activity and phosphorylation when cells were treated with PRL. Concluding that PRL affects EGF signaling upstream of MAPK, we examined the effect of PRL on EGF-induced Ras activity. NMuMG cells were incubated with [32P]orthophosphoric acid, treated as described above, immunoprecipitated with an antibody specific to Ras, and nucleotides were eluted and separated by TLC. Ras activity as measured by GTP:GDP ratio was increased by EGF, but not by PRL. Additionally, PRL in combination with EGF abolished the ability of EGF to induce Ras activity. Those studies suggest that PRL alters the EGF signaling pathway upstream of Ras. Because Ras activation by EGF involves EGF-stimulated association of EGF-R with Grb2, the EGF-R was immunoprecipitated and a Western blot was probed for Grb2. As expected we found that EGF stimulated an association of EGF-R with Grb2, PRL, however, blocked this association. When we looked at the ability of Shc to associate with the EGF-R, we found that PRL and EGF had little effect on this association. The studies demonstrate that PRL either directly or indirectly inhibits the ability of EGF to induce EGF-R association with Grb2, to activate Ras, and to activate and phosphorylate MAPK.
Peripheral vascular complications are a significant source of morbidity after coronary artery stent implantation. The goal of this study was to assess the incidence, risk factors, and management of vascular complications after stent placement. The study population consisted of 101 consecutive patients who underwent stent placement for either elective or bailout indications. All patients received a standardized anticoagulation regimen of aspirin, dipyridamole, low molecular weight dextran, heparin, and warfarin. Peripheral vascular access sites were examined daily until hospital discharge. Vascular complications occurred in 16 of 101 (16%) patients, including femoral artery pseudoaneurysm (n = 11), hematoma requiring transfusion or surgery (n = 4), and arteriovenous fistula (n = 1). Intervention was required in 14 of 16 (88%) patients with complications. These included transfusion (n = 7), ultrasound-guided compression (n = 8), and/or vascular surgery (n = 7). Length of hospital stay was prolonged in patients with complications (14 +/- 9 vs. 8 +/- 5 d, P < 0.001). The development of peripheral vascular complications did not correlate with clinical or procedural variables such as age, cardiovascular risk factors, arterial sheath size, or elective vs. bailout indication. After the introduction of a pneumatic vascular compression device (FEMOSTOP, C.A. Bard, Billerica, MA), a significant reduction in vascular complications was observed. Complications occurred in only 1 of 41 (2.4%) patients in whom the compression device was used in contrast to 13 of 58 (22.4%) patients compressed manually (P < 0.01). Thus peripheral vascular complications are frequent after coronary artery stent placement and are associated with serious morbidity and prolongation of hospital stay. These complications are significantly reduced by the use of a pneumatic vascular compression device despite intensive systemic anticoagulation.
Reports of the effects of trans fatty acids on coronary heart disease are inconsistent. Trans fatty acids may particularly influence coronary risk when linoleic acid levels are low, a situation which occurs in Scotland where prevalence of coronary heart disease is also very high. The link between trans fatty acid intake and prevalent coronary heart disease was therefore investigated in the Scottish Heart Health Study population. Trans fatty acid intakes were calculated from 10/359 sets of food-frequency questionnaire data obtained from the cross-sectional survey of men and women aged 40-59 years. Logistic regression analysis was used to calculate the odds ratios for prevalent coronary heart disease by fifths of dietary intake of total, natural and commercial hydrogenation-derived trans fatty acid. The group who had undiagnosed coronary heart disease at the time of survey was the pertinent group for examining the possible causative effects of trans fatty acid intake. After adjustment for the confounding factors (i.e. age, weight, height, smoking, level of physical activity, blood pressure, total energy intake and intakes of saturated fat, linoleic acid and the antioxidant vitamins) the odds of undiagnosed coronary heart disease for men, relative to the lowest intake fifth, did not differ significantly from unity by total or commercially-derived trans fatty acid intake. Odds were around 35% smaller in the higher intake fifths of naturally-derived trans fatty acids. For women, the odds of undiagnosed coronary heart disease tended to be greater in the higher fifths of total (odds ratio 1.36 (95% confidence interval 0.94, 1.89)) and hydrogenated (1.26 (0.92, 1.72)) trans fatty acid relative to the lowest fifth, but only reached significance in the third fifth of total trans fatty acid (1.36 (1.01, 1.83)). Dietary total and commercially-derived trans fatty acids failed to influence the odds of coronary heart disease for men, even though a significant increase in the ratio of low density plus very low density lipoprotein to high density lipoprotein-cholesterol occurred with trans fatty acid intake. The results, therefore, do not support a major effect of dietary trans fatty acid from commercial hydrogenation on coronary heart disease risk in these Scottish men. The results for women are less clear, and the possibility remains that individuals at the high extreme of trans fatty acid intake, who may be essential fatty acid deficient, are at enhanced risk of coronary heart disease.
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Renal transplantation is a relatively recent treatment option among the elderly with end-stage renal disease (ESRD). Since little is known regarding the clinical benefits of transplantation relative to dialysis in this age group, this study compares transplantation and dialysis among the elderly with respect to patient survival. Data utilized in this investigation were obtained from the Canadian Organ Replacement Register (CORR). The study population consisted of the 6400 patients aged 60 and over at registration, diagnosed between 1987 and 1993, for whom data on comorbid conditions were available. Survival probability, death rates, age-standardized mortality ratios (SMRs) and Cox regression analysis were employed to evaluate the survival experience among the transplant and dialysis groups. Transplant recipients were matched (by age, underlying diagnosis leading to ESRD, and number of comorbid conditions) to 2 randomly selected patients who did not undergo transplantation. Using Cox regression, the time-dependent hazard ratio for transplantation versus dialysis patients was estimated at 0.47 (P < 0.0001), indicating that even after adjusting for other known prognostic factors, elderly patients who received a transplant experienced significantly greater survival probability than those who remained on dialysis. When transplant patients were matched to randomly selected dialysis patients with the constraint that the corresponding dialysis patient have at least as much follow-up time as the transplant patient had waiting time, five-year survival rates were 81% and 51% for the transplant and dialysis groups, respectively (P < 0.0001). These results support the potential advantage of transplantation among the elderly, and may have important implications for renal care in this age group.
To assess the risk factors associated with renal osteodystrophy, we examined the database of 256 patients who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. The potential risk factors examined included age, sex, type and duration of dialysis, type and dose of phosphate binders, vitamin D treatment, and history of diabetes mellitus, renal allograft failure, parathyroidectomy, and bilateral nephrectomy. All patients had undergone a bone biopsy and were categorized into one of four disease groupings: (1) osteitis fibrosa and mixed bone disease, (2) aluminum bone disease, (3) mild bone disorder, and (4) aplastic bone disorder. The mean (+/- SD) age of the patients at bone biopsy was 57 +/- 15 years, and 62% were men. Forty-five percent of patients were treated by hemodialysis and 55% by peritoneal dialysis. The mean duration of dialysis was 4 +/- 4 years. Twenty-five percent were also diabetic. The most common disorder was the aplastic (or "adynamic") bone disorder, found in 34% of patients. Aluminum bone disease was found in 27%, osteitis fibrosa or mixed bone disease in 27%, and mild bone disorder in 12% of patients. Cumulative intake of aluminum gels was associated with aluminum bone disease, whereas peritoneal dialysis with supraphysiologic calcium concentrations, ingestion of calcium carbonate, and diabetes mellitus were associated with both mild bone disorder and aplastic bone disorder. These three latter risk factors may be important in predisposing patients to a low bone turnover state through modulation of parathyroid hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
We report here the demography and results of renal replacement therapy in Canada from 1981 to 1992. The new case rate for patients entering renal replacement therapy programs in Canada has increased dramatically over the last 12 years, from 49.9 per million to 98.4 per million of the population. The largest increases have been among the elderly, from 146.2 per million in 1981 to 381.9 per million in 1992 for those aged 65 to 74 years. There has been an even more dramatic increase for those over 75 years, from 83.6 per million in 1981 to 261.6 per million in 1992. There has been a similar increase in the prevalence rate, with an increase from 229.1 per million in 1981 to 518.5 per million in 1992. The hemodialysis rate for 1992 was 172.2 per million and that for peritoneal dialysis was 103.1 per million of the population. The renal transplantation rate also increased from 20 per million in 1981 to 34.8 per million in 1988, but unfortunately has decreased to 27.5 per million in 1992. Diabetes is now the most common primary renal diagnosis, having increased from 15% in 1981 to 24% in 1992. The 5-year survival rate of all patients on renal replacement therapy was 55%. For nondiabetic patients, the 5-year survival rate ranged from 85% for the those aged 15 to 44 years to 20% for those over 65 years. Among diabetic patients, the 5-year survival rate declined from 58% for the 15 to 44 year age group to 10% for those over 65 years.
Trans fatty acids produced during hardening of oils have been associated with higher cholesterol levels and increased risk of heart disease. The potential risk from trans fatty acids may be greater in populations with relatively low intakes of essential fatty acids such as the Scots, who also have a high prevalence of heart disease. Means and ranges of trans fatty acid intakes are reported here for a Scottish population. A semi-quantitative food-frequency questionnaire was used to survey the diet of 10,359 Scottish men and women aged 40-59 years in 1984-6 as part of the baseline Scottish Heart Health Study. Trans fatty acid levels were calculated for each food item on the questionnaire and the total subdivided into that which is derived naturally (primarily by bacterial fermentation in ruminants) and that which is produced during industrial hydrogenation (hardening) of vegetable and fish oils. Means and ranges of intakes of each trans fatty acid variable were calculated by sex, age, smoking and social class groups. Mean total trans fatty acid intakes for men were 7.1 (SD 3.1) g/d, 2.7 (SD 2.9)% energy and for women were 6.4 (SD 2.9) g/d, 3.3 (SD 3.0)% energy. Industrially hydrogenated trans fatty acids made up nearly 58% of the total intake for men and 61% for women, with about 60% coming from cakes, biscuits and sweets, and 20% coming from the cheaper hard margarines. The main sources of the naturally derived trans fatty acids were red meat (27%), milk (20%), butter (18-19%) and cheese (13-16%). Differences between age, smoking and social class groups were apparent. However, apart from the social class differences of up to 1 g/d, these were so small that they are unlikely to be of any biological significance unless compounded by other factors such as marginal essential fatty acid adequacy. The possibility of trans fatty acid intakes up to 48 g/d and 12% total energy (compared with the Department of Health (1991) recommendations of 5 g/d or 2% energy) highlights the need for careful monitoring of the health risks at these high levels of intake.
BACKGROUND: The objective of the study was to describe the design and sampling methods used to carry out face-to-face interviews with a sample of the black and ethnic minority population of the area. This study was conducted in the city of Bristol, England (part of Bristol and District Health Authority). METHODS: The sample was based on up to 1000 interviews with black Caribbean/African, South Asian and Far-East Asian residents. The design of the study focuses on the problems of definition of the appropriate group to sample and the various sampling techniques that were necessary to procure the interviews. RESULTS: A total of 574 interviews were carried out by bilingual interviewers matched for sex and ethnicity of the respondent, thereby allowing analysis that would be beneficial to the Health Authority in its planning and decision-making. CONCLUSIONS: The use of name spotting and 'snowball' sampling proved the most productive. The Electoral Register was preferred to the Family Health Services Authority lists. Interviewers must be carefully selected and adequately trained to work in this difficult area. The questionnaire must be culturally and linguistically acceptable across all the ethnic groups.
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