Jerry K. Aikawa

Alterations in the Body Potassium Content in Cirrhosis of the Liver

Summary Determinations of the exchangeable potassium content (Ke) by the radioisotopic method were performed on 13 subjects with cirrhosis of the liver, four of whom had ascites. Twelve of the 13 initial values were below the range found in normal subjects, the remaining value was in the lower normal range. Repeat determinations were performed on 6 subjects. The 3 subjects without ascites showed a significant increase in Ke following a week or more of treatment with a high protein, high carbohydrate, low fat diet, supplementary vitamins. In the 3 subjects with ascites no significant change in Ke occurred, even after the administration of an oral supplement of potassium. The results suggest that an intracellular deficiency of potassium is commonly present in cirrhosis of the liver, that this deficit is not correctable once hepatic decompensation has occurred.

Effects of digitoxin on exchangeable and tissue potassium contents.

Summary 1. The daily intravenous administration of 0.1 mg of digitoxin per kg of body weight to normal rabbits resulted, within 7 days, in an increase in body weight and a reduction in the serum potassium concentration and the exchangeable potassium content. These changes in potassium metabolism were corrected within one week by discontinuing the glycoside. 2. The intravenous administration of a single large dose of digitoxin (0.2 mg per kg) to normal rabbits resulted within 24 hours in a decrease in the mean potassium content of all the tissues and organs. Statistically significant decreases in potassium content were noted in the abdominal and diaphragmatic muscles and in the subcutaneous connective tissue. The results suggest that one of the effects of the administration of digitoxin in these dosages is to deplete the body store of potassium.

Effects of cortisone acetate on fluid and electrolyte balance in normal rabbits.

Summary 1. External balance studies for sodium and potassium and serial isotopic determinations of the exchangeable potassium content were made in 2 groups of normal male rabbits which were given, respectively, 4 mg of cortisone acetate daily for 2 weeks and 25 mg daily for 3 weeks. The administration of 4 mg daily resulted in an increase in body weight and a reduction in serum sodium concentration within 7 days; both serum sodium and serum potassium concentrations were increased in 14 days. One week after discontinuation of cortisone, the animals were in negative sodium balance. The administration of 25 mg daily resulted in a negative sodium and potassium balance with an increase in serum sodium concentration within 7 days. At 21 days, body weight and exchangeable potassium content were reduced. 2. The results indicate that the response of normal rabbits to cortisone acetate varies with the size of the dose and with the length of the period of administration. The results suggest that the earliest change to occur following the administration of a small dose daily was a retention of water in the extracellular fluid compartment; with continued administration of this dose, water was redistributed into the intracellular phase. The administration of a larger dose of cortisone daily resulted in depletion of the bodys store of potassium.

Measurements of the Disappearance of Radioactive Tagged Albumin from Serum and the Excretion of I181 in the Urine of Patients with Cirrhosis

Summary 1.A tracer dose of iodinated serum albumin was injected into 9 patients with cirrhosis of the liver and 22 patients with various other diseases. 2.The rate of disappearance of the tagged albumin from the vascular compartment was similar in the two groups. 3.A significant decrease in the excretion of inorganic iodide was found during the first 24 hours in the patients with cirrhosis.

Immunophysiology of serum sickness: Alterations in the blood volume and thiocyanate space in relation to humoral antibodies in rabbits sensitized with human albumin or globulin

Abstract 1.1. Alterations in the distribution of fluids associated with the development of humoral immunity were detected in rabbits injected intravenously with human serum albumin or globulin. 2.2. Increase in the space available for dilution of thiocyanate ions and decreases in plasma volume, total blood volume and hematocrit occurred at the time circulating antibody (precipitins) appeared. 3.3. The changes appeared earlier (at a mean of 7.1 days) following the injection of albumin than after the injection of globulin (9.0 days). Crystalline human serum albumin, injected subcutaneously, did not produce significant physiologic disturbances and the appearance of precipitins was delayed for a mean of 22.5 days. These findings were interpreted as indicating an alteration in antigenicity of the protein in the process of crystallization, but may have been related to the subcutaneous route of injection. 4.4. The redistribution of fluid was interpreted as indicating a defect in permeability of capillaries and of cell walls as a result of antigen-antibody reactions. 5.5. The correlation with anatomic findings by histologic techniques is discussed.

Effect of starvation on exchangeable potassium and tissue K42 content in rabbits.

Summary 1. Male rabbits were starved in order to study the effect of a decrease in food intake on potassium metabolism. 2. Serial determinations of the exchangeable potassium content and urinary potassium and creatinine excretion were made in one group of animals. The mean decrease in exchangeable potassiumcontent was 29.8 and 54.6% of the baseline value after one and two weeks respectively. The corresponding mean decrease was 15.6 and 31.7% in body weight. No significant changes in urinary creatinine excretion occurred. 3. In a separate group of rabbits, tissue analyses for radiopotassium and water concentration after one week of starvation revealed no significant changes when compared with control animals, continued on a constant diet. 4. The decrease in total body potassium content, as measured by the exchange of isotopic potassium, as well as the loss in the urine during starvation could be accounted for on the basis of tissue catabolism without postulating an intracellular deficiency of this cation in the remaining tissues. A functional abnormality in potassium metabolism may be detectable by the radioisotope method prior to its manifestation by the external balance method.

A BACTERIOLOGIC STUDY OF THE FACTORS AFFECTING THE EFFICACY OF STREPTOMYCIN THERAPY OF URINARY TRACT INFECTIONS

Streptomycin appears to be the most useful antibiotic available at present for the treatment of infections due to gram-negative bacilli. The absorption, distribution, and excretion of the drug following various modes of administration have been studied (1). The results of clinical trials of the drug in various types of infections have been reported (2). Treatment schedules and the influence of various factors in determining the optimum dosage of streptomycin have been investigated clinically, and the results are being reported elsewhere (3). The observation that the most common cause of therapeutic failure was the development of bacterial resistance or fastness 8 to streptomycin focused attention on the necessity for further bacteriologic studies in relation to concentrations of streptomycin. The cases of urinary tract infection afforded an opportunity for further investigation of the effect of streptomycin on bacteria.

Effect of cortisone acetate on experimental Rocky Mountain spotted fever in the guinea pig.

Summary 1. The effect of 2 different dosage schedules of cortisone acetate on guinea pigs infected with Rocky Mountain spotted fever of varying degrees of severity has been investigated. The overall mortality rate in 25 animals given daily intramuscular injections of 1 mg of the drug, starting on the day each received, by intraperitoneal injection, an inoculum of rickettsiae, did not differ significantly from the mortality rate in infected guinea pigs which received no treatment. The severity of the infection induced by different preparations of rickettsiae varied considerably; when this factor was taken into consideration, it appeared that cortisone acetate in doses comparable to those employed in human beings reduced the mortality rate in those animals with moderately severe infections. 2. In another group of 20 animals which received daily intramuscular injections of 25 mg of cortisone acetate for 5 days at the peak of the illness (fourth through the eighth day of infection) the overall mortality rate was identical with that in 20 infected animals not given the hormone. During the period of administration of this relatively huge dose of cortisone acetate, however, the fatality rate was significantly lower than that in the untreated animals.

Immunophysiology of immune reactions: Alteration in the thiocyanate space in quantitative passive transfer experiments in rabbits

Abstract In a further study of immunophysiology, the passive transfer method was utilized in rabbits in an effort to determine the possible relationship between in vivo antigen-antibody reactions and certain alterations in the plasma volume and thiocyanate space. In animals given intravenous injections of antibody, followed by the interscapular administration of specific antigen, an increase in the thiocyanate space was detected within 24 hours after injection of the antigen. Such a change was not observed in control animals given either specific antigen or antibody. This increase in the thiocyanate space has been interpreted as indicative of an abnormal increase in the permeability of cell membranes which was directly or indirectly due to the antigen-antibody reaction.

Isotopic studies of the body potassium content in thyrotoxicosis.

Summary 1. A radioactive isotope of potassium (K42) was used to determine the exchangeable potassium content (Ke) in 13 subjects with untreated thyrotoxicosis. The Ke values were lower in untreated thyrotoxic males than in normal male subjects. It is concluded that the low Ke values could be attributed to a decrease in the total muscle mass of the body, resulting from increased catabolism of body tissue. 2. In contrast to the results found in men, the values for Ke/wt in untreated women were normal, with one exception. This sex difference has been attributed to the dissimilarity in body composition normally found between males and females. It is postulated that in women mild or early thyrotoxicosis decreases the relative fat content of the body. Muscle tissue is extensively catabolized only after the store of fat has been depleted.