Lack of correlation between hepatic mitochondrial membrane structure and functions in ethanol-fed rats.

A current hypothesis suggests that alterations in the chemical composition and the subsequent changes in the structure of the membrane could account for the functional derangements observed in the hepatic mitochondria of animals fed ethanol for extended periods. An examination of this hypothesis reveals that the liver mitochondria of ethanol-fed rats show a dissociation between the respiratory functions and the lipid composition and microviscosity of the membranes.

Sublingual isosorbide dinitrate in severe congestive heart failure.

Sublingual isosorbide dinitrate was administered to 17 patients with severe congestive heart failure to characterize the hemodynamic action of the drug. Isosorbide dinitrate effect was maximal 30-60 min after administration. The most striking effect was a marked fall of the mean pulmonary capillary wedge pressure which dropped from 28 to 20 mm Hg (p less than 0.01). Pulmonary artery systolic pressure dropped from 55 to 43 mm Hg (p less than 0.01) and right atrial pressure from 11 to 8 mm Hg (p less than 0.01). Arterial blood pressure fell slightly whereas no significant change in heart rate or cardiac index was noted. 8 of the 17 patients showed a marked and sustained reduction of their pulmonary capillary wedge pressure. The hemodynamic response was moderate in 2 patients whereas 6 patients showed no appreciable improvement. A symptomatic but transient reduction in arterial blood pressure occurred in the last patient. Patients responding favorably to the drug had significantly higher initial systolic blood pressure that nonresponders (133 vs. 102 mm Hg, p less than 0.01). However, there was no reliable clinical parameter to predict which of the subjects will respond favorably to the administration of isosorbide dinitrate.

ASdult Fanconi's syndrome with renal tubular acidosis in association with renal amyloidosis: occurrence in a patient with chronic lymphocytic leukemia.

In a patient with chronic lymphocytic leukemia, multiple renal tubular defects developed in association with urinary excretion of K light chain proteins and peritubular deposits and casts of amyloid. Proximal tubular dysfunction, resembling adult Fanconi's syndrome, was suggested by an increased urinary loss of phosphate and urate and glycosuria. Renal tubular acidosis with hypokalemia and a marked impairment of the urinary concentrating mechanism were also observed.

Tubular handling of sodium and phosphate in cirrhosis with salt retention.

Tubular handling of sodium and phosphate were studied in 4 patients with cirrhosis and ascites. The control group consisted of 5 patients with cirrhosis without sodium retention. The degree of phosphaturia was assumed to reflect proximal tubular reabsorption. Whereas fractional excretion of phosphate was comparable in both groups, fractional excretion of sodium was strikingly diminished in the patients with ascites. This observation suggests that sodium retention in these patients occurs beyond the proximal tubule. This interpretation is in accord with our previous observation, based on clearance data, that the proximal tubular reabsorption of sodium in cirrhosis may be normal even in the face of edema formation.

Exaggerated natriuretic response to volume expansion in patients with primary biliary cirrhosis.

Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). This contrasts with the conspicuous tendency of patients with Laennec's cirrhosis to retain salt and water. In an attempt to clarify this clinical observation, renal handling of sodium was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone in five patients with PBC. These PBC patients were compared with two control populations: five edema-free patients with Laennec's cirrhosis and nine healthy volunteers. The natriuretic and diuretic response to ECVE was significantly greater in the patients with PBC as compared with the two control groups. CH2O for given rates of urine flow were similar in PBC patients as compared with normal subjects. The data suggest that a supranormal rejection of sodium at the proximal tubule in response to ECVE underlies the exaggerated natriuresis of PBC. The augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this variety of cirrhosis.

Renal tubular acidosis due to the milk-alkali syndrome.

A 60-year-old man with a history of excessive ingestion of calcium carbonate presented with azotemia, hypercalcemia and hyperphosphatemia. His acid-base status was initially normal. Following the cessation of calcium carbonate treatment, the hypercalcemia and azotemia disappeared, and the patient was found to be in metabolic acidosis with blunted acid excretion and a urine pH of 6.1. Kidney biopsy showed focal tubular calcification; the tubular damage was apparently caused by hypercalcemia and had resulted in renal tubular acidosis. During the three months of observation since that time there has been a tendecy for spontaneous remission of the renal tubular acidosis. Impaired renal hydrogen ion excretion prevented the development of metabolic alkalosis despite ingestion of alkali initially, and was later responsible for the metabolic acidosis. Renal tubular acidosis occurring as a sequel to the milk-alkali syndrome may aggravate the danger of nephrocalcinosis in this syndrome.

Renal handling of sodium, water and divalent ions in patients with primary biliary cirrhosis.

1) Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). In an attempt to clarify this clinical observation, renal handling of sodium, water and divalent ions was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone (ADH) secretion in 5 patients with PBC and 9 normal subjects. 2) Mean fractional excretion of sodium, water, phosphate and calculated fractional distal delivery of sodium were significantly greater in patients with PBC as compared with normal controls. Fractional CH20 for given fractional urine flow was similar in patients with PBC and normals. 3) The data suggest that patients with PBC have a greater diminution of proximal tubular reabsorption of sodium in response to ECVE than controls. This augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this type of cirrhosis.