Normal subjects, normal-renin hypertensive patients, and low-renin hypertensive patients were evaluated by intravenous saline infusion and with a fludrocortisone acetate (Florinef) protocol to clarify diagnostic criteria for primary aldosteronism that are recommended for the saline infusion protocol. The patients consumed a 200 mEq sodium, 70 mEq potassium diet for 6 days, and on the last 3 days received Florinef 0.5 mg orally twice daily. On Days 3 and 6, urinary aldosterone and tetrahydroaldosterone excretions were determined, and on Days 4 and 7 plasma aldosterone (PA) was determined at 0600 after overnight recumbency and at 0800 after 2 hours of walking. Although the level of normal PA suppression by saline infusion has been commonly defined as 10 ng/dl, a value of 5 ng/dl was originally recommended. In 20 normal subjects and 45 normal-renin hypertensive patients, we found that the PA was almost always suppressed below 5 ng/dl. In 18 of 75 low-renin patients including five with aldosterone-producing adenoma (APA), the PA was never suppressed below 10 ng/dl; thus, these 18 patients had classical primary aldosteronism by generally accepted criteria. The Florinef protocol was performed in eight of these 18 patients and was abnormal in all. An abnormal Florinef protocol was also found in seven of 15 patients studied with PA suppression after saline infusion to between 5 and 10 ng/dl, but in only one of 24 patients studied with PA suppression below 5 ng/dl. Additional studies in the subgroup with abnormal results from the Florinef protocol indicated that none of these patients had evidence of APA, so they had nontumorous primary aldosteronism (NTPA).(ABSTRACT TRUNCATED AT 250 WORDS)

The polyribosomal fraction from chicken embryo fibroblasts infected with B77 avian sarcoma virus contained 38S, 28S, and 21S virus-specific RNAs in which sequences identical to the 5'-terminal 101 bases of the 38S genome RNA were present. The only polyadenylic acid-containing RNA species with 5' sequences which was detectable in purified virions had a sedimentation coefficient of 38S. This evidence is consistent with the hypothesis that a leader sequence derived from the 5' terminus of the RNA is spliced to the bodies of the 28S and 21S mRNA's, both of which have been shown previously to be derived from the 3' terminal half of the 38S RNA. The entire 101-base 5' terminal sequence of the genome RNA appeared to be present in the majority of the subgenomic intracellular virus-specific mRNA's, as established by several different methods. First, the extent of hybridization of DNA complementary to the 5'-terminal 101 bases of the genome to polyadenylic acid-containing subgenomic RNA was similar to the extent of its hybridization to 38S RNA from infected cells and from purified virions. Second, the fraction of the total cellular polyadenylic acid-containing RNA with 5' sequences was similar to the fraction of RNA containing sequences identical to the extreme 3' terminus of the genome RNA when calculated by the rate of hybridization of the appropriate complementary DNA probes. This suggests that most intracellular virus-specific RNA molecules contain sequences identical to those present in the 5'-terminal 101 bases of the genome. Third, the size of most of the radioactively labeled DNA complementary to the 5'-terminal 101 bases of the genome remained unchanged after the probe was annealed to either intracellular 38S RNA or to various size classes of subgenomic RNA and the hybrids were digested with S1 nuclease and denatured with alkali. However, after this procedure some DNA fragments of lower molecular weight were present. This was not the case when the DNA complementary to the 5'-terminal 101 bases of the genome was annealed to 38S genome RNA. These results suggest that, although the majority of the intracellular RNA contains the entire 101-base 5'terminal leader sequence, a small population of virus-specific RNAs exist that contain either a shortened 5' leader sequence or additional splicing in the terminal 101 bases.

The arrhythmogenic potential of diuretic-induced hypokalemia in patients with uncomplicated hypertension has been controversial. Thirty-two hypertensive patients with previous diuretic-induced hypokalemia, normal 24-hour ambulatory ECG monitoring, and normal exercise testing were treated with 100 mg hydrochlorothiazide (HCTZ) daily (Group 1) to induce hypokalemia or with a combination of HCTZ with amiloride (Group 2) to attempt to maintain plasma potassium levels in the normal range during diuretic therapy. Those Group 1 patients (Group 1A) with increased ventricular ectopic activity (VEA) during HCTZ therapy were subsequently potassium-repleted with amiloride and with supplemental potassium chloride to evaluate the effect of these treatments on VEA. One Group 1 patient died suddenly after 12 days of HCTZ therapy. Autopsy findings suggested an arrhythmic death. Six Group 1 patients who had increased VEA with HCTZ treatment had reductions in VEA with amiloride or supplemental potassium chloride. Group 2 patients did not have a significant increase in VEA. Thus, diuretic therapy appears to cause VEA primarily by electrolyte changes that are induced.

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