Renal failure and the histopathological features of myeloma kidney reversed by intensive chemotherapy and peritoneal dialysis.
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Biomedical subjects
Publications and source records attributed to R McGonigle.
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The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony-forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.
Renal cell carcinoma tissues from two patients, one with and one without erythrocytosis, were successfully transplanted into athymic nude mice. Transplantations of the erythrocytic tumor through six successive generations of nude mice produced a significant (P less than 0.001) elevation in mean hematocrit from 36.5 +/- 2.1% (range 32-42%) to 53.7 +/- 5.1% (range 40-63%), in comparison with a non-erythrocytic tumor which showed a progressive fall in hematocrit from 46.5 +/- 2.0% (range 41-50%) to 36.8 +/- 1.6% (range 33-40%). Non-grafted control nude mice maintained stable hematocrit levels from an initial level of 45 +/- 0.5% to 46.5 +/- 1.2% when studied over the same time interval. Similarly red cell mass values in the mice transplanted with the erythrocytic tumor (5.04 +/- 1.85 ml/100 g) were considerably higher than in both the non-grafted nude mice (3.39 +/- 0.81 ml/100 g) and the non-erythrocytic tumor-grafted mice (3.8 +/- 0.3 ml/100 g) after 6 generations of transplants. Plasma erythropoietin levels in the erythrocytic tumor-grafted mice (169.4 +/- 83.1 mU/ml) were significantly (P less than 0.02) higher than in the non-grafted controls (22.2 +/- 9.5 mU/ml), and furthermore the erythropoietin levels in the tumor extracts were significantly (P less than 0.02) higher in the tumors from erythrocytic mice (range 54.7 to 234.6 mU/g tumor) than in the tumors from non-erythrocytic mice (range 0.3 to 1.9 mU/g tumor). In vitro monolayer cultures of these tumors confirmed the higher erythropoietin levels in the erythrocytic renal carcinoma (138 mU/ml) as compared with culture media of non-erythrocytic tumors (15-91 mU/ml) using the fetal mouse liver assay (59Fe incorp. into heme). The present studies indicate autonomous erythropoietin production by human renal cell carcinomas both in vivo in nude mice and in vitro in tissue cultures.
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A five-year follow-up study of the effects of treating patients with both mild and moderate hypertension was performed. The patients were identified during a hospital-based community survey of hypertension. A total of 961 patients were divided into four groups. The first group, the controls, were age- and sex-matched normotensive subjects selected sequentially from the same survey. The second group were patients defined as well-controlled hypertensives; the third group were patients whose blood pressures were less well-controlled; and the fourth group consisted of patients who, for various reasons, were not treated and as such acted as an untreated control group. Both mortality and morbidity were considerably greater in the untreated patients than in the normal subjects. The well-controlled hypertensive patients showed no difference in either morbidity or mortality from normal subjects. The less well-controlled patients had a significantly greater cardiovascular morbidity but no excess mortality over groups 1 and 2. This was true for both mild and moderate hypertension and for women as well as men. These findings therefore confirm the conclusions of other recent studies that good control of hypertension at all levels and in both sexes is justified by the reduction in morbidity and that even less than excellent control is of considerable benefit.
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Pneumonia due to Mycoplasma pneumoniae is common, but it is rarely life-threatening. A case is reported in a previously healthy adult whose illness was severe enough to require treatment with intermittent positive pressure ventilation (IPPV) for 14 days and which resolved after treatment with corticosteroids.
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During the 6-year period 1981-1987, 309 patients started chronic ambulatory peritoneal dialysis (CAPD), of whom 75 (24%) had diabetes. Despite severe peripheral vascular problems (20%), ischaemic heart disease (90%), and complete blindness (21%) the 1-year patient survival on CAPD was 88%. The actuarial patient survival for diabetic patients was similar to that of the non-diabetic cohort over the first 18 months but fell to 48% (compared to 70% in non-diabetic patients) at 3 years. Complications associated with CAPD, including the incidence of peritonitis, were no different between the diabetic and non-diabetic patient populations. Successful treatment for end-stage renal disease (ESRD) in diabetic patients can be achieved and justified in a liberal selection programme for the treatment of diabetic ESRD.