No abstract

Aluminum levels were measured in a variety of tissues obtained from 36 control subjects, 30 nondialyzed uremic patients, 57 dialyzed uremic patients dying of a variety of different causes, and 38 dialyzed uremic patients dying of dialysis encephalopathy. The low aluminum levels consistently found in the control tissues support the fact that in health aluminum is largely excluded from the body. However, this ability to prevent aluminum accumulation is overcome with renal failure. Bone and liver aluminum levels were found to be significantly increased in 82% and 56% respectively in nondialyzed uremic patients and in 100% of the tissues examined from dialyzed uremic patients. In patients dying of dialysis encephalopathy, tissue aluminum levels were not only the highest but also affected in a different manner than that found in other dialyzed patients. It is suggested that dialysis encephalopathy occurs as a result of such rapid aluminum loading during dialysis that bone's ability to sequester this element is overcome, and it is shunted to liver and brain with resulting toxicity.

EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with gout excreted significantly more excess lead chelate than those without gout. In the gout group 17 patients denied any childhood or industrial exposure to lead. They had a greater number of positive tests and excreted significantly more excess lead chelate than 14 patients with neither gout nor lead exposure. These results confirm that gout in the presence of chronic renal failure is a useful marker of chronic lead poisoning. Of 27 patients with positive lead mobilization tests, only 13 had elevated XRF finger bone lead concentrations (sensitivity 48%). Three of 15 patients with negative lead mobilization tests had elevated XRF finger bone lead concentrations (specificity 80%). Although the XRF finger bone lead test is a convenient noninvasive addition to the diagnostic evaluation of patients with chronic renal failure and gout, its application is limited due to the lack of sensitivity of the method.

Urinary excretion of lead (Pb) was measured in the basal state and following the infusion of EDTA (1 g of calcium disodium edetate) in healthy German controls and in patients with chronic renal failure with and without gout. When evaluated with Zeeman-compensated atomic absorption spectroscopy using the L’vov platform and urine pretreated with nitric acid and Triton X-100, the control basal Pb excretion (median 28, range 11–19 nmol Pb/24 h) and the postinfusion Pb increment (306, range 131–1,587 nmol/4 days/1.73 m²) were considerably lower than most values reported previously in the literature. Elevated Pb body burden was found in 7 of 8 patients who developed gout in the course of renal failure, but only in 2 of 8 patients who had gout prior to development of renal failure; this confirms that appearance of gout in patients with renal failure points to prior Pb exposure. In 7 of 19 nongouty patients with impaired renal function secondary to known renal diseases, urinary Pb excretion was above the 95th percentile of normal. All these patients had occupational Pb exposure. The high prevalence of elevated Pb body burden in patients with renal failure of known cause may not be coincidental and raises the possibility that Pb adversely affects the course of renal disease.

No abstract

We compared propranolol with methyldopa in a randomized prospective study of 28 women with pregnancy associated hypertension. Both drugs were equally effective in controlling maternal hypertension. There was no significant difference in the birthweights of the babies in each group. However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia. The mean peak levels of propranolol, propranolol glucuronide, 4-hydroxypropranolol, and 4-hydroxypropranolol glucuronide were not significantly different in the first, second, third trimesters and at least 3 months post partum. The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels. Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk, being approximately 0.1% of the maternal dose.

No abstract

Metolazone, a new diuretic/saluretic/anti-hypertensive agent related to quinethazone, was used to treat 20 patients with impaired renal function. Among eight water loaded hospitalized patients given metolazone 5 mg intra venously, glomerular filtration rate rose in four and diminished slightly in four while urine flow and sodium excretion in creased significantly. In 12 out-patients given long-term oral metolazone (usually 5–10 mg in single daily doses) treatment effectively removed oedema and induced weight loss; in the seven initially hypertensive patients blood pressure decreased also. Plasma renin activity was measured in seven patients before and after several weeks’ metolazone therapy. Activity fell in two patients and rose in five, but the upper limit of normal was exceeded in one only. Renal epithelial cell excretion rates indicated that drug nephrotoxicity was absent. Mean creatinine clearances rose, serum potassium levels fell, and ten patients received oral potassium supplements. Small transient increases in liver enzymes were seen in three patients. Metolazone tended to maintain glomerular filtration rate and renal plasma flow while increasing salt and water losses. A proximal as well as a distal site of action was suggested for the drug, and its anti-hypertensive effect was confirmed.