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Biomedical subjects

U F Michael

Publications and source records attributed to U F Michael.

33 records · Page 2Linked to original sources

Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose.

A multicenter study of chlorthalidone was performed to determine the relative antihypertensive efficacy and side effects of doses lower than those usually recommended for therapy. After a 4-wk placebo control period 100 patients with mild hypertension were randomly assigned doubleblind to 12.5-, 25-, 50-, or 75-mg regimens of chlorthalidone or to placebo for 12 wk. The groups of patients taking 25, 50, and 75 mg had declines in blood pressure which were not significantly different from each other. Serum potassium decreased in the 50- and 75-mg groups but not significantly in the 25-mg group. We conclude that chlorthalidone, 25 mg daily, was at least as effective for hypertension as 50 and 75 mg with less perturbation of potassium. Use of smaller initial diuretic doses may provide equal efficacy with fewer side effects for many patients.

Adult↗

Polyuric syndromes.

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Diabetes Insipidus↗

Impaired urinary acidification in the hypothyroid rat.

Since abnormalities in the renal handling of sodium and water in both the proximal and distal tubule have been described in primary hypothyroidism, this study was undertaken to examine renal tubular hydrogen secretion in this disorder. Metabolic acidosis was induced in hypothyroid rats (H) and their age matched controls (C) by the administration of an oral ammonium chloride load of 0.15 g/24 h/kg for three days. On day 3 animals were prepared for clearance and acid-base studies, receiving an infusion of Ringer's solution of 0.6 ml/hr/100 g during surgery and the experimental procedure. A 26% decrease in GFR (P less than 0.005) and a doubling in fractional excretion of sodium (P less than 0.02) were observed in H rats. The lowest blood pH and average bicarbonate concentration and the excretion of chloride were similar in the two groups, indicating that the acid load was reabsorbed and led to similar degrees of systemic acidification. Urine flow also was comparable in the two groups. Minimal urine pH after NH4Cl was 6.21 +/- 0.06 in H and 5.68 +/- 0.09 in C (P less than 0.001). Ammonium excretion was 28% (P less than 0.05) lower in H than in C. The defect in urine acidification in H was only partially corrected after 5 days on a low sodium diet and DOCA administration for 2 days. Fractional bicarbonate excretion at normal blood pH and bicarbonate concentration was not different in the two groups. These data indicate that hypothyroid rats have a mild defect in urine acidification and that it is localized predominantly in the distal tubule.

Acidosis, Renal Tubular↗

Antihypertensive effectiveness of oxprenolol administered twice daily.

Oxprenolol, a beta-blocker, is an effective antihypertensive when administered 3 or 4 times daily. We evaluated the antihypertensive effect of oxprenololgiven twice daily (bid). The subjects were 15 ambulatory men whose standing diastolic blood pressure (BP) was at least 100 mm Hg after 3 wk of treatment with hydrochlorothiazide and oxprenolol placebo. Oxprenolol 40 mg twice daily was then substituted for the placebo. On subsequent weekly vists oxprenolol was titrated to 80 and 160 mg bid if the standing diastolic BP was greater than 90 mm Hg. BLood pressures on the last visit on placebo were compared to those on the last visit on oxprenolol. Standing BP declined from 145 +/- 4/108 +/- 1 to 130 +/- 4/98 +/- 4 on a mean dose of 256 mg of oxprenolol (p less than 0.001 syst.; p less than 0.01 diast.). Recumbent BP fell from 146 +/- 4/107 +/- 1 to 138 +/- 5/93 +/- 2 (p less than 0.06 syst.; p less than 0.01 diast.). During the final week, 13 of the 15 patients were admitted to the hospital for 24-hr monitoring of BP. The 24-hr BP readings showed a mean coefficient of variation of 6.6% recumbent and 7.2% standing. we conclude that bid oxprenolol will maintain 24 hr BP control in most patients.

Administration, Oral↗

Antihypertensive effects of oxprenolol and propranolol.

The antihypertensive effects of the beta blockers oxprenolol and propranolol were compared in a randomized double-blind study of patients with standing diastolic pressures (SDP) exceeding 99 mm Hg when receiving hydrochlorothiazide alone. After 3 wk of hydrochlorthiazide with placebo, the latter was replaced with oxprenolol (n= 12) or propranolol (n = 14), 20 mg three times daily. Beta blocker was increased subsequently to 40 and 80 mg three times daily if SDP exceeded 89 mm Hg. Nine oxprenolol and 7 propranolol subjects were hospitalized for 24-hr monitoring. With oxprenolol, standing pressure declined from 135 +/- 2 (SE)/104 +/- 1 MM Hg to 128 +/- 3/90 +/- 2. SDP declined to under 91 mm Hg in 7 of 12 subjects, and to from 91 to 95 in 3 subjects. With propranolol, findings were 138 +/- 3/106 +/- 2 to 123 +/- 3/89 +/- 3; in 7 of 12 to less than 91 mm Hg and from 91 to 95 in 4 subjects. Decrements in supine and SDP were slightly (4 mm Hg) greater for propranolol than for oxprenolol. Both drugs gave similar 24-hr blood pressure control. We conclude that oxprenolol and propranolol used to supplement hydrochlorothiazide provide comparable reductions in blood pressure and smooth control over a 24-hr period in most patients with hypertension.

Adult↗

Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat.

Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.

Animals↗

Impaired renal concentrating ability in hypothyroid man.

The renal concentrating ability was studied in ten patients with hypothyroidism and in 15 euthyroid controls. Solute-free water reabsorption was reduced in the patients with myxedema (4.2 +/- 0.3 ml/min: controls 5.8 +/- 0.6 ml/min; p less than 0.01). This defect was apparent at high rates of solute excretion, and was associated with enhanced excretion of sodium (p less than 0.01) despite a decreased filtered load (p less than 0.005). The myxedema patients had a modest reduction in maximal urine osmolality (p less than 0.04), which was entirely attributable to the lower values observed in younger patients. The results may be explained best by decreased sodium chloride reabsorption in the ascending limb of Henle's loop and/or diminished permeability of the distal nephron in myxedema.

Adult↗

Renal acidification in hypothyroid man.

The role of thyroid hormone in renal hydrogen ion secretion remains largely unknown, and there is only limited information on renal acidification in hypothyroid patients. In the present study two of five adult male patients with untreated primary hypothyroidism and without clinical evidence of systemic autoimmune disease were unable to lower their urine pH appropriately after short duration acid-loading. Since, prior to acid-loading, their arterial blood gas values were within the normal range and urinary bicarbonate excretion was trival, the findings are consistent with the incomplete syndrome of distal renal tubular acidosis. Although the mechanism of this abnormality remains unknown, thyroxine deficiency per se may in part be responsible.

Acidosis, Renal Tubular↗

Calculation of O2 saturation and of the oxyhemoglobin dissociation curve for different species, using a new programmable pocket calculator.

The degree of O2 saturation and different data of acid-base status are determined from pO2, pH, and pCO2 values bya programmable pocket calculator. Since the operating program should be usable for different species and also in the range of very low O2 saturations, obviously the usual Hill equation for calculating the oxygen dissociation curve of hemoglobin is not applicable; the same is true is some cases for the Adair equation. Thus a 3-fold subdivision of the dissociation curve was undertaken and programmed. Suitable programs for several species could be established despite the limited number of program steps in the new calculator, giving systematic deviations in calculated O2 saturations of less than or equal to +/- 0.9 saturation precent over the full range of dissociation curves. A reverse procedure for calculation of pO2 from saturation is added. In situations where pCO2 or base excess are not known or only estimated, limits of the arising error are stated. In the acid-base program 7 parameters are evaluated partially using empirical formulae derived from nomograms. The programmable pocket calculator offers advantages of small size, economy, and independence of line voltage compared to much more spacious units and a precision equal or superior to nomograms.

Animals↗

Renal function in the choline deficient rat.

Abnormalties in renal concentrating ability and free water reabsorption, and a diminished sodium excretion, glomerular filtration rate, and effective renal plasma flow were observed in adolescent rats which ingested a lipotrope deficient diet for 10 months.

Animals↗

Renal handling of sodium and water in the hypothyroid rat. Clearance and micropuncture studies.

Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals. Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P](IN)) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats. These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron.

Absorption↗

Cimetidine disposition in patients undergoing continuous ambulatory peritoneal dialysis.

Cimetidine disposition was determined in six patients undergoing continuous ambulatory peritoneal dialysis to ascertain the need for modification of conventional dosing regimens. Blood, dialysis fluid, and urine were collected for 48 hours after administration of a single intravenous dose of cimetidine. The following values were obtained: elimination half-life, 4.3 hours; systemic or total body clearance, 191 +/- 55 ml/min; and dialysis clearance, 4.2 +/- 3.1 ml/min. Approximately 2% of a cimetidine dose is removed by dialysis, indicating that there is no need to adjust the conventional renal failure dosing regimen in patients undergoing continuous ambulatory peritoneal dialysis.

Aged↗