Synergistic action of metolazone with "loop" diuretics.
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Biomedical subjects
Publications and source records attributed to R R Ghose.
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A redundant nickel/cadmium battery worker was investigated for non-specific fatigue after completing five years in the industry. Sensitive techniques for in-vivo organ cadmium measurement showed a moderate accumulation in the liver but a very large concentration in the kidneys. Despite this, overall glomerular and tubular function were not impaired. It was concluded that the mechanism of proteinuria observed in some cadmium workers is obscure and not clearly related to the degree of kidney saturation with cadmium.
Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured pre- and post-parathyroidectomy in 9 patients with primary hyperparathyroidism. Radiological studies had shown no sign of renal calculi or nephrocalcinosis in these patients. Before operation, GFR ranged from 98.5 to 23.4 ml/min/1.7 m2 and ERPF ranged from 510 to 127 ml/min/1.7 m2. After operation, GFR rose to a range of 108.8 to 48.7 ml/min/1.7 m2, and ERPF ranged from 556 to 189 ml/min/1.7 m2. The results suggest that early diagnosis and surgery are important, both to prevent progressive renal damage and to improve the possibility of recovery where functional damage has occurred.
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A patient with protracted vomiting was noted to have hyponatraemia and hypokalaemia on admission. Isotope dilution studies before treatment revealed profound body depletion of sodium, potassium and water. Treatment with potassium chloride tablets produced a simultaneous rise in serum sodium and potassium concentration without change in urine volume or osmolality, or body weight. Potassium depletion appears to have contributed to the mechanism of hyponatraemia in this situation, and that replacement of potassium corrected hyponatraemia by effectively re-distributing solute and water across the cell membrane, so that sodium ions which had entered intr-cellular fluid during electrolyte depletion, subsequently returned to extracellular fluid after treatment.
A patient with long-standing ischaemic heart disease and severe low output congestive cardiac failure received numerous diuretics, which gradually became ineffective. Resistant oedema was treated by adding demeclocycline to the current diuretic regime of frusemide and metolazone. Diuresis resulted, oedema disappeared and body weight fell. This drug combination was continued without complication for a further 6 months until his death.
A patient with hypocalcaemia and hypomagnesaemia secondary to small bowel resection and malabsorption was treated with synthetic vitamin D analogue, 1-alpha hydroxy vitamin D3. A prompt rise in serum calcium concentration and some days later a smaller and transient rise in serum magnesium concentration was observed. These changes in extracellular fluid composition presumably resulted from enhanced calcium and magnesium absorption associated with vitamin D activity.
1 Six previously untreated emergency admissions to hospital with severe hypertension were given oral treatment with labetalol. 2 Pre-treatment diastolic BP exceeded 130 mmHg, and clinical evidence of either accelerated hypertension or encephalopathy was present. 3 Hypotensive response after treatment followed two patterns. 4 Quick-responders (n = 3) showed a sharp fall in BP to normal levels within 2 h, which was subsequently sustained for 10 or more hours. The daily dose of labetalol eventually required to achieve good BP control in this group was relatively low: 600--1200 mg. 5 Slow-responders (n = 3) showed a gradual, less marked fall in BP, which was sustained for many hours. These patients required further doses of labetalol to reduce BP to normal. The eventual daily dose of labetalol that ensured good BP control was high: 1200--2400 mg. 6 Heart rate was little changed by treatment. 7 Complications or side-effects were not observed.
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Nine patients with persistently elevated diastolic blood pressure, exceeding 130 mmHg, received an oral dose of labetalol ranging from 200 mg to 400 mg. In all patients, this produced a significant and gradual decline in recumbent systolic and diastolic blood pressure, unaccompanied by symptoms or complications, with only minor changes in heart rate. Individual variation in the rate of blood pressure fall suggested differences in absorption and first-pass metabolism. It is suggested that the efficacy of oral labetalol merits further investigation in the rapid control of severe hypertension.
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