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Biomedical subjects

M Walser

Publications and source records attributed to M Walser.

At least 127 records · Page 7Linked to original sources
PubMed1977

Neonatal citrllinemia: treatment with keto-analogues of essential amino acids.

A patient with neonatal onset citrullinemia survived to 8 months of age when treated with a mixture of essential amino acids and their keto-analogues. The initial plasma citrulline concentration was 2.7 mM; the blood ammonia concentration was greater than 500 muM. During the first week of therapy, the blood ammonia concentration became normal and that of plasma citrulline was reduced by almost 50%. It was possible to institute progressive increases in dietary calories and protein; growth and developmetn with resolution of almost all clinical signs of disease ensued. The patient died at 8 months of age after an episode of diarrhea and dehydration, probably of viral origin.

Amino Acid Metabolism, Inborn Errors↗
PubMed1977

Effects of oral neomycin and kanamycin in chronic uremic patients: I. Urea metabolism.

The fate of portal ammonia derived from intestinal urea degradation was examined in 15 experiments in patients with chronic renal failure. The kinetics of labelled urea metabolism were studied before and again during the administration of oral neomycin or kanamycin. Detectable absorption of both drugs generally occurred, but urea clearance and estimated glomerular filtration rate did not significantly change during antibiotic administration. In seven experiments a significant fall in urea degradation (65% to 95%) occurred during antibiotic administration. Analysis of the effect of antibiotics was confined to these seven experiments. In the control periods, there were no differences in urea metabolism or renal function between these patients and those in whom urea degradation was not suppressed. If ammonia derived from urea degradation is converted back to urea in the liver, then suppression of degradation would lead to an equal decrease in urea production, and the difference between production and degradation ("appearance") would remain constant. However, if urea-derived ammonia is used for protein synthesis, suppression of degradation would permit the formerly degraded urea to appear in urine and body fluids and thus to increase urea appearance. In these seven experiments, we found no change in urea appearance during antibiotic administration. We conclude that portal ammonia is reincorporated into urea in chronic renal failure and is not utilized significantly for protein synthesis.

Administration, Oral↗
PubMed1977

Effects of oral neomycin and kanamycin in chronic uremic patients: II. Nitrogen balance.

Nitrogen balance was studied for five to seven days before and during oral administration of neomycin or kanamycin to 14 patients with severe chronic renal failure who were receiving long-term nutritional therapy consisting of protein restriction and supplements of essential amino acids or their nitrogen-free analogues. There was a significant improvement in nitrogen balance during the antibiotic period when compared to the control period, averaging +0.80 g of N per day (P less than 0.005). There was no significant change in average dietary nitrogen, fecal nitrogen, the excretion of non-urea urinary nitrogen, or urea appearance (defined as the sum of urinary urea and the change in the urea pool) during the antibiotic period. However, total nitrogen intake increased by 0.47 g per day owing to nitrogen contained in the drugs. The lack of a change in fecal nitrogen implies that fecal nitrogen not attributable to the drug must have fallen substantially. We conclude that oral neomycin and kanamycin may improve nitrogen balance in patients with severe chronic renal failure by diminishing endogenous fecal nitrogen.

Administration, Oral↗
PubMed1977

The role of alanine and glutamine in steroid-induced nitrogen wasting in man.

1. Administration of dexamethasone, 8 mg/day (0-02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion 2. In eight subjects ingesting 0-9--1-6 g of protein day-1 kg-1 body weight the cumulative increment in urea nitrogen excretion averaged + 12-5 g (SEM 2-8, P less than 0-01) over the 5 days of glucocorticoid administration. 3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation. 4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance. 5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.

Adult↗
PubMed1977

Amino acid metabolism of dog jejunum before and during absorption of keto analogues.

In fasting dogs, significant uptake by the jejunal wall from arterial blood was found for glutamine and eight other amino acids. Significant release into the mesenteric vein of ammonium, alanine, citrulline, and proline occurred, equal in nitrogen content to glutamine nitrogen taken up. The keto analogues of leucine, valine, and isoleucine, infused for 1 h into the lumen at initial concentrations of 10mM, disappeared from the lumen at 20.2 +/- 1.6, 18.6 +/- 2.0, and 15.7 +/- 2.8 mumol/cm in 1h, respectively. Eight fifteen and seventeen percent, respectively, of these absorbed quantities were released into mesenteric blood as leucine, valine, and isoleucine plus alloisoleucine, indicating significant amination of the keto acids by the gut wall. No significant changes were detected in the arteriovenous differences of any other amino acids or ammonium. The remainder of the absorbed analogues of valine and isoleucine appeared as such in the blood. In the case of the keto analogue of leucine, there was apparent degradation by the gut wall of 34% of the absorbed compound.

Amino Acids↗
PubMed1977

Bicarbonate ions in active sodium transport across toad bladder.

The conductance, ga, and electromotive force, E, of active ion transport across toad bladders mounted as sacs were estimated from electrical measurements made before and after addition of sufficient ouabain (1.89 X 10(-3) M) to eliminate spontaneous potential. The ratio of net sodium transport (estimated from bidirectional fluxes) to external current in bladders voltage clamped to 0 mV was significantly less than unity in a normal medium containing HCO3- and Cl- ions, and also when Cl- was replaced with SO42-. However, when acetazolamide was added or when HCO3- was replaced by phosphate, short-circuit current and net sodium transport became equal. Spontaneous potential, E, and ga were all reduced about 20% by these maneuvers. The response of bidirectional sodium fluxes to voltage clamping at 0 mV or 120 mV in a bicarbonate-free medium was otherwise similar to that observed in a normal medium: net flux varied linearly with potential and calculated fluxes in the active transport path indicated a value significantly greater than unity for the empirical constant Q in the equation for change in the flux ratio, f, with change in potential, psi, viz., delta ln f = Q(ZF/RT)delta psi, similar to the high value for this constant that we have found in a bicarbonate-containing medium. We conclude that bicarbonate ions facilitate active sodium transport and also may be actively transported from serosa to mucosa in Dominican toads. However, coupling between bicarbonate and sodium fluxes does not account for the high value for Q for sodium in the active transport path.

Animals↗
PubMed1977

Nitrogen balance of uremic patients receiving branched-chain ketoacids and the hydroxy-analogue of methionine as substitutes for the respective amino acids.

The efficacy of the D,L-alpha-hydroxy analogue of methionine and the alpha-keto analogues of valine, leucine and isoleucine as substitutes for the corresponding amino acids was tested by measuring the nitrogen balance of chronic uremic patients receiving glycine as their source of nitrogen while eating a virtually protein-free diet. Calcium salts of the following essential amino acid analogues: 2.01 g D,L-2-hydroxy-4-methylthiobutyrate, 2.70 g 2-oxoisovalerate, 3.80 g of 2-oxoisocaproate, and 2.73 g of 2-oxo-3-methylvalerate, plus the remaining five essential amino acids were given to five patients daily for 5--7 days. Nitrogen balance, corrected for urea accumulation (but not for unmeasured cutaneous losses of nitrogen) averaged +1.24+/- 0.39 g/day. We conclude that this mixture and dosage of amino acid analogues can meet the dietary requirements of chronic uremic patients for methionine, valine, leucine and isoleucine.

Amino Acids, Essential↗
PubMed1976

A simple method of estimating progression of chronic renal failure.

In 31 of 34 patients with chronic renal insufficiency caused by various diseaes, reciprocal serum-creatinine concentration declined linearly as creatinine concentration rose from a mean of 2-6 mg/dl to 14-8 mg/dl over an average of 71 months. These results indicate that in most cases reciprocal serum-creatinine declines linearly with time as chronic renal failure progresses. Analysis of this relation in individual patients gives an estimate of the progression of the disease, may help to determine the effects of therapy, and could be used to predict when dialysis will become necessary.

Creatinine↗
PubMed1976

Effect of transepithelial concentration gradients on the passive fluxes of sodium across toad bladder.

Bidirectional sodium fluxes across toad bladder were measured after eliminating active transport with ouabain. Mucosal sodium concentration, Cm, was progressively reduced (from 114 to 3 mM) while serosal sodium remained constant. Potential difference was maintained at zero by current passage. The ratio, Q, of the bulk permeability coefficient for sodium, P, to the tracer sodium permeability coefficient, P, was found to remain constant as Cm decreased. Equations were derived on this basis for bidirectional fluxes and for P and P as functions of Cm, which corresponded closely to the observed data. The explanation for the observed value of Q and its constancy under these conditions is uncertain.

Animals↗
PubMed1976

Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids.

A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia.

Adolescent↗
PubMed1976

Effects of keto analogues of essential amino acids in portal-systemic encephalopathy.

Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.

Administration, Oral↗
PubMed1975

Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids.

Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia.

Adolescent↗
PubMed1975

Sodium fluxes through the active transport pathway in toad bladder.

To assess the active components of sodium flux across toad bladder as a function of transepithelial potential, unidirectional sodium fluxes between identical media were measured before and after adding sufficient ouabain (1.89 X 10(-3)M) to eliminate active transport, while clamping transepithelial potential to 0, 100 or 150 mV. Evidence was adduced that ouabain does not alter passive fluxes, and that fluxes remain constant if ouabain is not added. Hence, the ouabain-inhibitable fluxes represent fluxes through the active path. Results were analyzed by a set of equations, previously shown to describe adequately passive fluxes under electrical gradients in this tissue, here modified by the insertion of E, the potential at which bidirectional sodium fluxes (beta E, and theta E) through the active pathway are equal. According to these equations, beta E and theta E are the logarithmic mean of bidirectional fluxes through the active path at any potential, and the flux ratio in this path is modified by a constant factor Qia, which represents the ratio of the bulk diffusion coefficient to the tracer diffusion coefficient in this pathway. The data are shown to conform closely to these equations. Qia averages 2.54. Hence, serosal-to-mucosal flux vanishes rapidly as potential falls below E. Mean E in these experiments was 158 +/- 1 mV. Thus, linear dependence of net flux in both active and passive pathways on potential is present, even though the sodium fluxes in both paths fail to conform to the Ussing flux ratio equation. Qip less than 1 in the passive path (qualitatively similar to exchange diffusion) and Qia greater than 1 in the active path (as in single file pore diffusion). Both of these features tend to reduce the change in serosal-to-mucosal sodium flux induced by depolarization from spontaneous potential to zero potential ("short-circuiting").

Animals↗
PubMed1975

Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats.

Weanling male rats were fed diets containing essential amino acids as the sole source of nitrogen at a level of either 6 or 15% by weight of the diet. When L-valine was replaced isonitrogenously by calcium L-alpha-hydroxyisovalerate in the 15% amino acid diet, growth ceased and urea excretion increased; urea clearance was unaffected. When L-leucine was replaced isonitrogenously by calcium L-alpha-hydroxyisocaproate in this diet, growth and feed efficiency fell approximately 60% and urea excretion rose, but urea clearance doubled. L-Phenylalanine was replaced both isonitrogenously and without supplemental glutamate by calcium L-phenyllactate in both the 6 and 15% amino acid diets and was also added in twice equimolar quantities to the 6% amino acid diet. When the 15% amino acid diet was fed, growth was severly reduced, but when the 6% diet was fed, the double dose of phenyllactate reduced growth and feed efficiency only 25%. Urea clearance was not consistently altered. When D,L-methionine was replaced by calcium K,L-alpha-hydroxy-gamma-thiobutyrate in the 15% amino acid diet, growth and feed efficiency improved whether or not glutamate was added to make diets isonitrogenous, and also whether or not 0.1% neomycin was included. Urea clearance did not differ among these groups but was significantly higher in rats receiving the hydroxy analog or D,L-methionine than that in controls receiving L-methionine. Thus, the ability of these hydroxy analogs to replace the corresponding amino acids in the diet of rats varies from complete (methionine) to partial (leucine and phenylalanine) or virtually nonexistent (valine).

Animal Nutritional Physiological Phenomena↗
PubMed1975

Ketoacids in the treatment of uremia.

Essential amino acid supplementation (EAA) was compared with supplementation by a mixture (KA) of keto-analogues of valine, leucine, isoleucine, methionine and phenylalanine, plus the four remaining essential amino acids in stable chronic uremics. When KA were given after EAA, urea appearance fell and N balance improved (9 studies). When EAA were given after KA (5 studies), urea appearance and N balance did not worsen significantly during the 4-9 days of observation. Seven patients, including one on chronic dialysis prior to therapy, were given KA for 3-9 months as outpatients. In three, renal function clearly improved. Five became asymptomatic for intervals of 3-8 months.

Adult↗