Harold A. Harper

A clinical study of the effect of arginine on blood ammonia

Abstract 1.1. The ability of intravenously administered L-arginine hydrochloride to decrease the blood ammonia was investigated in fifteen patients with elevation in blood ammonia and varying degrees of encephalopathy associated with several disease entities. 2.2. In every case there was a reduction in the ammonia levels of the blood following arginine therapy. Improvement in the mental status of the patient accompanied the fall in blood ammonia. Two of three patients with severe viral hepatitis who were given arginine while in deep coma responded in twenty-four to thirty-six hours with marked clinical and biochemical improvement and eventual recovery. 3.3. The decrease in the level of ammonia in the blood that occurred after administration of arginine was always accompanied by a significant rise in the blood urea nitrogen, suggesting that the effect of arginine on the blood ammonia may be mediated through its role in the urea cycle. 4.4. Further clinical experiences with substances such as arginine which can effectively lower the blood ammonia should serve to delineate more clearly the pathologic importance of ammonia intoxication in clinical desease.

Renal clearance of eighteen individual amino acids in human subjects.

Studies of renal clearance of individual amino acids have been comparatively few in number. With the exception of those of Sheffner, Kirsner, and Palmer (1) such investigations have been performed solely on experimental animals and in certain respects the results which they have yielded have been conflicting. In part, the conflict has arisen because of the limited specificity of the analytical methods which the earlier investigators were forced to employ (2-7). Beyer and his associates (8-12), and Kamin and Handler (13), using the more specific methods of microbiological assay, were able to define these areas of conflict as well as to confirm and extend certain of the earlier findings. The most important findings of these previous investigations and the present state

The causes of histidinuria in normal pregnancy

Abstract Renal clearance studies were conducted on 10 normal pregnant women who were receiving intravenous infusions of inulin and l -histidine at a constant rate. The plasma and urinary levels of the amino acid were determined microbiologically. Identical studies were repeated on the same individuals four to seven weeks after delivery. All subjects had increased histidinuria while pregnant, with marked increases in histidine clearance. Three factors were found to account for this: 1. 1. The rate of glomerular filtration was increased in all 10 subjects from a nonpregnant mean of 104 to a pregnancy mean of 171 ml. per minute per 1.73 sq. M. of body surface. This change accounted for about half of the excess histidine excreted. 2. 2. The percentage of the filtered histidine which was reabsorbed by the renal tubules was decreased during pregnancy in every subject, accounting for about one-fourth of the excess histidine excreted. 3. 3. The rate at which the injected histidine entered the intracellular compartment of the body was decreased by pregnancy from a mean of 1.015 ± .04 to a mean of 0.81 ± 0.15 Gm. per hour. This reduction, statistically significant, causes an elevation of the plasma histidine level sufficient to account for the remainder of the excess histidine excreted. It is not known whether the altered metabolism is due to a decrease in the rate of histidine breakdown, or in the rate of histidine utilization, or both.

Concentrations of nineteen amino acids in plasma and urine of fasting normal males.

Summary The plasma and urine levels of 19 free amino acids as determined microbiologically in fasting, healthy, young males are reported.

Renal clearance of lysine in cystinuria: Pathogenesis and management of this abnormality

Abstract Cystinuria is an inherited abnormality in which unusually large amounts of cystine, lysine, arginine and ornithine are excreted in the urine. Simultaneous measurements of the inulin and lysine clearances indicate that in the fasting state a very small amount of lysine is reabsorbed from the glomerular filtrate. The renal tubules are unable to reabsorb any additional amount and, on loading with lysine, their clearance value approaches that of inulin. A suggested explanation for this tubular defect is that in the homozygous form of cystinuria the transport system is present in only trace amounts. The transport system may be of the membrane carrier type and its limited capacity is exceeded even in the fasting state. Any reabsorption which does occur is accomplished by an active mechanism and passive diffusion plays no role of significance. Patients with cystinuria respond normally to the administration of glycine and arginine in that the excretion of glycocyamine is increased. Therapeutic efforts directed at the specific tubular defect appear to hold little promise. The decrease in cystine excretion which can be accomplished by dietary restriction should not be neglected. The addition of a methyl donor to a restricted dietary intake offers no additional advantage. Measures directed at rendering the physicochemical environment less conducive to precipitation deserve further study.

Cerebral Metabolism of Glutamic Acid in Multiple Sclerosis

CURRENT STUDIES concerning the pathogenesis of multiple sclerosis are increasingly being directed toward altered metabolic processes. The present investigation deals with cerebral metabolism in multiple sclerosis, and particularly with the metabolism of glutamic acid and its amide glutamine in patients suffering from varying stages of the disease. There is now available a suitable method for measuring the rate of cerebral blood flow (CBF) that permits a computation of the rate of utilization or liberation by the brain of any substance that can be accurately analyzed in blood.’ By means of this technic, the rates of CBF and the cerebral metabolic rates (CMR) for oxygen, carbon dioxide, glucose, lactic acid, pyruvic acid, as well as for glutamic acid and its amide glutamine have been measured in patients with multiple sclerosis and in a series of normal control subjects. A total of 32 patients with multiple sclerosis have been studied. The patients for the most part were admitted to the University of California Hospital, where a complete investigation of their clinical status was made and where they were independently examined by several members of the departments of neurology and neurosurgery. No patient was included in the study unless the clinical findings and subsequent course established the diagnosis of multiple sclerosis. The patients were divided into three groups: 1. Those in an acute active exacerbation of the disease, or patients in an initial attack who subsequently were shown to have multiple sclerosis. 2. Those with advanced multiple sclerosis who, at the time of the study, evinced no signs of active progression of the disease. The disease in this stage has been termed “indolent multiple sclerosis.’’ 3. Those who were either improving from an active exacerbation or recovering from an initial attack of the disease. The average age of the patients with multiple sclerosis was 31 years (range

The effect of portacaval shunting on gastric secretion in cirrhotic dogs.

Summary Cirrhosis of the liver was induced in dogs with gastric pouches by the administration of a mixture of carbon tetrachloride and alcohol. The resulting gastric hypersecretion was augmented by 201 per cent to 510 per cent after portacaval transposition although this shunting procedure did not in itself cause any further decline of hepatic function.

The preparation and microbiological evaluation of the inhibitory effects of some acrylic acid derivatives.

Abstract The following acrylic acid derivatives have been prepared and microbiologically evaluated as possible inhibitors of the growth of lactobacilli; indoleacrylic acid, β-(2-quinolyl)-, β-(3-quinolyl)-, β-(4-quinolyl) acrylic acids, cinnamic acid, p -hydroxycinnamic acid, p -dimethylaminocinnamic acid, p -diethylaminocinnamic acid, thienylacrylic acid, furylacrylic acid, and α-ethylacrylic acid. The utilization of tryptophan by Leuconostoc mesenteroides P-60 and Lactobacillus arabinosus was inhibited by the isomeric quinolylacrylic acid derivatives as well as by indoleacrylic acid. With this latter compound and the β-(3-quinolyl)acrylic acid, competitive inhibition was shown. p -Hydroxycinnamic acid inhibited the utilization of phenylalanine and tyrosine by all the organisms tested. At similar concentrations neither cinnamic acid nor phenol exerted any inhibitory effect. The effects of all inhibitors could be at least partially reversed by the addition of larger quantities of the corresponding amino acids.

Aminoaciduria in an Elderly Man with the Nephrotic Syndrome and in a Young Man with a Variant of the Fanconi Syndrome

Excerpt Normally, in a fasting human subject, almost all of the amino acids filtered at the glomerulus are reabsorbed (1). If the filtered load of an amino acid is increased, both the amount reabso...

Excretion of amino acids in nephrosis.

Summary (1) By microbiological assay, concentrations of 18 amino acids have been examined in the blood and urine of patients with nephrosis and in normal individuals under various circumstances. There were observed in an adult male patient, with nephrotic syndrome associated with glomerulonephritis, large increases over the normal rates of urinary excretion of many amino acids, both essential and nonessential, but more notably of the essential. A female adult patient, with clinical findings only of nephrosis, showed considerably less deviation from normal with a trend toward increased excretion of amino acids in the fasting state. There was a general tendency to moderately low concentrations of several amino acids in the blood of both nephrotic subjects. 2) After elevation of the blood concentrations by intravenous loading of a mixture of amino acids, the percentage of filtered amino acids (determined by simultaneous measurement of inulin clearance) which were excreted generally increased in the case of normal individuals as well as in the nephrotic subjects. No. consistent differences could beobserved between normal and nephrotic subjects as a result of “loading” of the blood with amino acids. 3) Intravenous administration of ACTH for 9 to 10 days to 2 normal subjects and 1 nephrotic subject produced no distinct changes in rates of excretion of amino acids in the normal individuals. but appeared to be associated with a moderate decrease in excretion of virtually all amino acids in the patient with nephrosis. Further study is required to confirm this observation.