Diastolic dysfunction and abnormality of the Na+/Ca2+ exchanger in single uremic cardiac myocytes.

Cardiovascular disease is the most common cause of death in patients with end-stage renal disease, possibly due to a specific "uremic cardiomyopathy". This study investigated the function of the Na(+)/Ca(2+) exchanger in single cardiac myocytes from a model of early renal impairment. Mild uremia was induced by partial (5/6) nephrectomy in male Wistar rats. After 4 weeks, ventricular myocytes were isolated, loaded with the fluorescent Ca(2+) indicator indo-1, and contractile function and calcium transients recorded following electrical pacing at 0.2 Hz. Relaxation from rapid cooling contractures (RCCs) was also studied. Cells from uremic animals (U) were hypertrophied compared with controls (C), with a significant increase in width (14%; P<0.02) and cross-sectional area (13%; P<0.03). There was a significant increase in diastolic intracellular Ca(2+) ratio in the uremic cells (C, 0.33+/-0.00 vs U, 0.37+/-0.02; P<0.02), although the amount of calcium released per twitch was similar. Uremic cells were slower to relax following RCCs, however when Na(+)/Ca(2+) exchange was inhibited using a Na(+)-free/Ca(2+)-free solution, this difference was abolished. Under these conditions, there was little difference in the relaxation rate of control cells, indicating that the Na(+)/Ca(2+) exchanger plays only a minor role in relaxation in normal rat myocytes. However in uremia, the data indicate that the Na(+)/Ca(2+) exchanger actively interfered with relaxation, possibly by working in reverse rather than forward mode. These results indicate that myocyte relaxation and Ca(2+) handling are abnormal in early uremia and may provide further evidence for the existence of a specific "uremic cardiomyopathy".

Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with anti-thyroid drug treatment.

Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis following treatment with propylthiouracil and carbimazole are described. Both patients had crescentic glomerulonephritis proven by renal biopsy and responded to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though systemic vasculitis associated with propylthiouracil is reported, this is the first report to our knowledge of renal biopsy-proven vasculitis associated with either of these drugs.

Bromide psychosis: a literary case.

Author Evelyn Waugh, noted for such works as Brideshead Revisited, published in 1957 an autobiographical account of his own bromide psychosis in the novel The Ordeal Of Gilbert Pinfold. Until now, however, the fact of his bromide poisoning had gone unrecognized both in biographies of Waugh and in analyses of the novel. Ordeal gives a detailed, accurate, day-by-day description of bromide psychosis. This unusual, witty, and fascinating piece of literature actually provides the most complete monograph on the subject. In this article we review the literature on bromide poisoning, discuss the events of the novel and of Waugh's life in light of his bromide psychosis, and suggest the relevance of the case to medicine.