Continuous ambulatory peritoneal dialysis in Australia, Europe, and the United States: 1981.
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Biomedical subjects
Publications and source records attributed to P C Farrell.
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The inclusion of activated charcoal within hemodialysis membranes offers potentially improved plasma clearance of creatinine and middle molecules. However, the carbon becomes saturated with continued use and beyond 1 h removal of solutes is by dialysis alone. Two independently conducted crossover studies, to assess the efficacy of sorbent membrane dialysis (SMD) in the treatment of uremia, found predialysis urea levels increased by approximately 15%, creatinine by 10-15%, and inorganic phosphate levels by 10-18% on SMD compared to conventional hemodialysis. One study also observed "middle molecule' (peak "b') levels elevated. No differences were observable in the clinical status of patients. The results suggest that the charcoal content of the SMD device is too small to effect any advantages over conventional dialysis.
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A chromatographic method for separating uremic middle molecules has been developed, based on a modification of the method of Fürst et al. to permit accurate and rapid (less than 3.5 hours) determination of UMM levels. Semiautomation of the equipment has also resulted in 3 analyses per 8-hr working day. Comparison of UMM results in patients on a carefully controlled study of long (mean 7.5 hr) versus short (mean 3.6 hr) hours of hemodialysis indicate that UMM levels are higher on short dialysis but only peaks 7ao, 7a, 7b, and 7c1 show significant but relatively unimpressive differences between the two regimens. UMM levels have also been obtained in long-term CAPD patients. Data show that UMM levels remain stable, over at least 12 months of CAPD and all UMM levels are lower than in hemodialysis patients. From analysis of generation rate data there is also an indication that UMMs may be dietary related.
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A modification of a two-stage chromatographic procedure (molecular sieve followed by ion-exchange) to separate potentially toxic uremic "middle molecules" from body fluids has been established. The procedure has an analysis time less than half that previously reported with improved resolution. Elution volumes have been found to be reproducible to within 2% and concentrations (as measured by peak height) to within 10%. Careful attention, however, must be paid to artifacts that may arise from sample preparation, drug therapy, and dialysis conditions. Up to ten identifiable subpeaks were observed in sera, urine, and red cell hemolysate samples following ion-exchange separation of a molecular sieve peak in the middle molecule range (300 to 2000 daltons). Red cell concentrations of five of these moieties were significantly higher than those in serum. Four peaks were not detected at all in red cells, and one peak was not detected in sera or urine samples. In addition, although serum concentrations are elevated in uremia, red cell levels in patients with uremia are comparable with those obtained in normal subjects. If any of these species are subsequently shown to be uremic toxins, then their two-compartment distribution within the body has important ramifications in the choice of an appropriate mathematic model to program optimal dialysis therapy.
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