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Biomedical subjects

F Marsh

Publications and source records attributed to F Marsh.

27 records · Page 2Linked to original sources

Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.

Adult↗

Silicone-induced hypercalcaemia in haemodialysis patients.

Silicone spallation from the roller-pump insert in dialysis blood lines leads to the accumulation of silicone in haemodialysis patients, which in turn leads to a foreign-body reaction with granuloma formation. We have studied two patients in whom documented silicone accumulation has been associated with both granuloma formation and significant, persistent hypercalcaemia. In both patients plasma levels of immunoreactive parathyroid hormone and 1,25-dihydroxyvitamin D were low or undetectable. In one patient, hypercalcaemia responded only partially to corticosteroids, but completely to naproxen. Both patients were changed to silicone-free blood lines and their hypercalcaemia subsequently resolved. The results indicate that in some haemodialysis patients, silicone accumulation and granuloma formation may lead to hypercalcaemia that is independent of 1,25-dihydroxyvitamin D, and that may instead reflect altered prostaglandin metabolism.

Adult↗

Multi-centre study on outcome of treatment in patients on continuous ambulatory peritoneal dialysis and haemodialysis.

In a multi-centre study by seven large renal units in the United Kingdom, the morbidity and mortality of all patients starting CAPD and haemodialysis during a 2-year period (1983-1984) has been monitored prospectively and related to reasons for choice of therapy and potential risk factors. Over this period 338 new patients (mean age 48; range 3-77 years) started CAPD; 17% had diabetes mellitus and 25% had cerebro/cardiovascular disease. One hundred and seventy-five patients (mean age 45; range 5-73 years) started haemodialysis; 6% had diabetes mellitus and 14% had cerebro/cardiovascular disease. The Kaplan-Meier actuarial patient survival estimates at 2 years were haemodialysis 84% and CAPD 83%, whilst technique survival figures for the same period were haemodialysis 92% and CAPD 80%. Cox's regression analysis showed that cerebro/cardiovascular disease and age greater than 60 years were most important predictors for survival in CAPD patients, in whom smoking appeared to be a significant risk factor, for permanent change of therapy to haemodialysis. The major cause of 'drop out' in both groups was transplantation, whilst hospitalisation was 14.9 days per patient year for CAPD and 12.8 for haemodialysis patients. Within the CAPD group a temporary change to haemodialysis (less than 2 months) occurred on 106 occasions (each of mean of 19 days duration), amounting to 10 days per patient year of therapy. CAPD was used twice as often as haemodialysis for managing new patients. After 2 years hospitalisation technique and patient survival were comparable in the two groups, with cerebro/cardiovascular disease, age, and smoking being significant predictors of outcome.

Adolescent↗

Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminum toxicity.

Neurofibrillary material was found in cortical neurons in two patients who died with dialysis encephalopathy. The cytoplasm of these neurons contained large amounts of aluminum and whole-brain and blood aluminum levels were high. These findings suggest that in dialysis encephalopathy aluminum has a specific effect on neuronal protein synthesis, resulting in the accumulation of neurofilaments in cortical neurons. This neurofibrillary neuronal degeneration resembles that found in experimental aluminum toxicity, but differs in several respects from the neurofibrillary tangles characteristic of Alzheimer's disease.

Adult↗