Opiate toxicity in patients with renal failure.
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Biomedical subjects
Publications and source records attributed to W E Nelson.
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BACKGROUND: Progressive deterioration in renal function occurs in 20-50% of patients with idiopathic membranous nephropathy (IMN). Several treatment regimens have been used to reverse this with varying effect and toxicity. METHODS: Thirteen patients (10 males, 3 females, median age 56 years) with IMN and progressive renal failure were treated with oral prednisolone 20-60 mg/day and azathioprine 1.3-2.7 mg/kgBW/day. All patients were followed up for a minimum of 2 years with a median follow-up of 73 months (range 24-103 months). RESULTS: Ten patients responded to treatment with a fall in serum creatinine and renal function stabilized in the remainder. Two patients relapsed, one of whom responded to an increase in immunosuppression, the other is now on dialysis. Proteinuria has significantly reduced in 10 patients, and only four patients still have nephrotic-range proteinuria. Mean (+/- SE) peak pretreatment serum creatinine of 229 (+/- 161) mumol/l and urinary protein of 11.8 (+/- 1.8) g/24 have fallen to 163 (+/- 65) mumol/l and 3.25 (+/- 1.0) g/24 h after 12 months treatment (P < 0.005, Wilcoxon matched pairs test). Immunosuppressive treatment has been successfully withdrawn in four patients after intervals ranging from 12 to 60 months. Adverse effects, which occurred in 10 patients, have been mild and have not led to treatment withdrawal though dose reductions have been necessary in some patients. CONCLUSIONS: Oral prednisolone and low-dose azathioprine is an effective therapy for progressing renal failure due to IMN, and induces remission of nephrotic syndrome. Side-effects are less than other immunosuppressive regimens.
This study objectively evaluates recovery of quadriceps and hamstring strength following knee arthroscopy in a group of 43 patients given rehabilitation instructions, but limited supervised rehabilitation. Although the patients did not complain of weakness or functional limitation, isokinetic testing 1, 3, and 8 weeks following surgery revealed persistent weakness in many patients. Incomplete recovery was most apparent when patients were categorized by the degree to which they had recovered normal strength. Results expressed as a mean for the entire group indicated reasonably good recovery and obscured the significant weakness persisting in some patients. Knee extension strength tested at 60 degrees/sec had returned to normal 8 weeks after arthroscopy in only 32% of the subjects. Hamstring strength recovery was better, with 71% having normal strength. Patients may not recognize or report muscular weakness following arthroscopy, yet following 8 weeks of self-supervised rehabilitation many will have objective evidence of persistent weakness. In asymptomatic patients the clinical significance of this weakness is unknown.
In a retrospective analysis of 202 renal transplant procedures in the years 1989-1992 we identified an excess of grafts lost from primary renovascular thrombosis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) compared to haemodialysis (HD) patients (9 CAPD versus 0 HD, Chi-squared = 9.63; P < 0.01). All graft losses from thrombosis occurred within 16 days of surgery. Possible predisposing causes were identified in three patients. Donor age was greater in CAPD patients losing their kidneys from thrombosis compared to the overall CAPD group [mean (SD) years, 43.0(12.9) versus 29.1(15.8); P = 0.01] whereas no significant difference in haematocrit, platelet count, antibody status, cyclosporin use, peroperative hypotension, primary diagnosis, smoking, or diabetes mellitus was found. Data from the EDTA registry for 1990-91 show that graft loss from primary renovascular thrombosis in UK-treated patients was reported in 7.1% of CAPD recipients compared with 1.8% in haemodialysis. We suggest that CAPD patients are at greater risk of graft loss from renovascular thrombosis than HD patients and may require more intensive fluid and anticoagulant treatment in the perioperative period.
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Twenty-three patients with end-stage renal failure due to diabetic nephropathy received renal replacement treatment. All patients had insulin-dependent diabetes mellitus. Nineteen transplants were performed in seventeen patients. Two-year graft survival for all transplants was 74% with a two-year patient survival post-transplantation of 81%. Overall two-year patient survival was 73%, compared with 82% in non-diabetic patients receiving renal replacement treatment. In diabetic patients accepted for treatment there was a high incidence of non-renal complications, particularly vascular disease. An aggressive approach to the treatment of vascular disease in these patients may improve overall survival rates.
We have recently completed the field work phase of a 4-year prospective study of football-induced minor head injuries. Players from 10 University football teams were monitored up to 4 years, and a brief neuropsychological and psychosocial assessment battery was administered to them up to five times before and after injury. Objectives of this project focus on the frequency of head injuries in college football, the impairments that might result from such injury, the duration of impairments, the time course of their recovery, and the possibility of cumulative effects of multiple injuries during the player's college career. Approximately 2500 players were monitored during the study, and nearly 200 players were restudied following minor head injuries. A series of nearly 60 players with orthopedic injuries were tested using the same protocol, and a college student control series of 50 patients were similarly studied. Data analyses are currently underway, and the first report of the findings of this study will be available soon. This article has described the objectives and design of this study, outlined the neuropsychological and psychosocial assessment protocol, and discussed some of the issues related to project implementation. Current data analyses focus on the size of the effects of minor head injury on cognitive and psychosocial performance observed following minor head injury. Upon completion of the initial data analyses, our analysis plan includes having at least two neuropsychologists make independent assessments of the clinical significance of the findings. Similar assessments will be made of the neurophysical symptoms and complaints and psychosocial performance of players after injury.
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Plasma prednisolone concentrations were measured in 26 renal transplant (RT) patients and five control subjects. A linear relationship was found between prednisolone dosage in mg/kg and area under the plasma concentration time curve in seven stable RT patients (r = 0.98) and in all subjects (n = 19) with estimated prednisolone clearance rates (CLp) between 0.075 and 0.11 L/kg/hr (r = 0.96). The greatest deviation from this occurred in five patients having reduced CLp with prolonged prednisolone half life (t1/2p) and in one having increased CLp while taking phenytoin. Three of the five with reduced clearance had steroid induced diabetes and one a Cushingoid appearance. There was some correlation between peak plasma prednisolone and dosage (r = 0.77) in all subjects, but none between creatinine clearance and t1/2p or CLp.
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