A proposal to help new house officers.
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Internship and Residency↗
Biomedical subjects
P D Lief
Publications and source records attributed to P D Lief.
Effect of cyclic AMP on hydrogen ion secretion by turtle urinary bladder.
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Animals↗
Use of diuretics in treatment of hypertension secondary to renal disease.
Eleven patients with hypertension secondary to renal disease were treated with hydrochlorothiazide or furosemide plus other drugs to normalize blood pressure. Creatinine clearance fell during the initial treatment period, but then either remained constant or rose toward pretreatment levels in spite of continued therapy. Plasma renin activity was low-normal to subnormal in eight of the 11 patients prior to therapy and did not rise significantly with therapy. Aldosterone excretion was within the normal range prior to treatment and remained normal or increased moderately with treatment. This study demonstrates that diuretics effectively reduce blood pressure in patients with hypertension secondary to renal disease without producing severe volume depletion or clinically significant reduction in renal function. The low renin levels are consistent with other evidence that hypertension in these patients is related to salt and water retention.
Adult↗
Diagnosis of lupus nephritis by skin immunofluorescence, in the absence of extrarenal manifestations of systemic lupus erythematosus.
Six patients with glomerulonephritis were found to have granular deposits of complement and/or immunoglobulins at the dermalepidermal junction of normal skin. No patient had extrarenal clinical manifestations of systemic lupus erythematosus (SLE). The only serologic test suggestive of SLE was a positive antinuclear antibody (ANA) reaction; results of complement and antinative deoxyribonucleic acid (DNA)-antibody tests were repeatedly normal. The patients with glomerulonephritis had a favorable initial response to therapy with prednisone with or without azathioprine. These patients may represent a variant of SLE in which the diagnosis can only be established by a direct immunofluorescence test of normal skin. Alternatively, they may constitute a separate new clinical entity. Because of the favorable response to therapy, we suggest that skin immunofluorescence be performed in patients who present with unexplained glomerulonephritis and a positive ANA.
Adolescent↗
Effect of stretch on passive transport in toad urinary bladder.
In order to gain further information about the effect of stretch on the urinary bladder of the toad, transepithelial movement of radioactive sucrose, chloride, and urea was measured across bladder sacs during acute changes in the internal volume. Short-circuit current (SCC) and total tissue conductance (Kt) were also measured in each experiment. It was found that sudden large increases or smaller graded increases in volume resulted in a consistent fall in the tracer permeability (P*) of all three isotopes. However, this fall was due entirely to the larger area term in the calculation of P* rather than any real change in isotope movement. When total diffusion (TD) of each isotope was calculated by a method that eliminated the changes in surface area, it was apparent that stretch produced no significant effects on the transepithelial movement of any of these three molecules. Large stretch also resulted in parallel increases in SCC and Kt in most bladders. We conclude from these observations that the intercellular pathway for sucrose and chloride and the transcellular pathway for urea are unaltered by degrees of stretch that enhance SCC and sodium transport. By inference, the observed increases in Kt appear to represent changes in specific active pathway conductance (Ka), and may relate importantly to the changes in sodium transport.
Animals↗
The behavior of carbenicillin as a nonreabsorbable anion.
In order to study the mechanism of hypokalemic alkalosis which occurs in some patients being treated with disodium carbenicillin, renal clearance experiments were carried out in rats and observations were made on electrical changes in isolated toad bladders. In rats maintained on a sodium-free diet, intravenous infusion of carbenicillin at 40 mg. per hour resuited in an immediate diuresis characterized by a striking increase in K and NH4 excretion, and progressive acidification of the urine. In a control group of rats, also prepared with a sodium free diet, intravenous infusion of mannitol resulted in a comparable diuresis, but no significant changes in K and NH4 excretion, and no acidification of the urine. The urinary changes in the carbenicillin-treated rats could not be accounted for by any alterations in blood electrolytes, acid-base values, or glomerular filtration rate (GFR). Isonatric, isohydric substitution of carbenicillin for chloride in the mucosal bathing media of toad bladders mounted in Ussing chambers resulted in a reversible increase in electrical potential (PD) and resistance (R) without a comparable change in short-circuit current (SCC). Substitution in the serosal medium resulted in a reversal of polarity of PD and SCC in 4 of 9 experiments, a finding best explained by more rapid movement of chloride from M leads to S than carbenicillin movement from S leads to M (a chloride diffusion potential). The observations in both the rat and toad bladder experiments are consistent with the view that carbenicillin behaves as a nonreabsorbable anion. Hypokalemic alkalosis in patients receiving this drug can thus be attributed to increased electrical negativity of the distal nephron with subsequent enhancement of K and H secretion.
Acid-Base Equilibrium↗