3-Amino-2-piperidone in the urine of patients with hyperornithinemia.

3-Amino-2-piperidone, a delta-lactam of ornithine, has been detected in the urine of a number of patients with hyperornithinemia. The distinctive yellow colour formed with a ninhydrin-cadmium reagent should help in the detection of hyperornithinemia by urinary chromatography.

Increased excretion of N-carbamoyl compounds in patients with urea cycle defects.

Increased urinary levels of N-carbamoyl-beta-alanine, and also, on occasions, of N-carbamoylaspartate, were observed in patients with ornithine carbamoyl-transferase (EC 2.1.3.3) deficiency, argininosuccinate synthetase (EC 6.3.4.5) deficiency and argininosuccinate lyase (EC 4.3.2.1)deficiency, but not in a patient with carbamoylphosphate synthase deficiency. The relevance of these findings to the diagnosis of urea cycle defects is discussed.

An alternative way of presenting quantitative amino acid results.

An application of computer graphics is described which enables quantitative plasma amino reports to be presented pictorially in a way which enhances the quality of the information.

Plasma carnosinase deficiency in patients with urea cycle defects.

A complete absence of plasma carnosinase activity was observed in a series of patients with proven urea cycle defects. This finding could not be explained by age of patients, low protein intake, or inhibition of the enzyme by glutamine or carbamyl phosphate.

Increased pyroglutamic acid levels in patients on artificial diets.

Increased plasma and urine levels of pyroglutamic acid were found in 4 patients being fed the low-lactose food Nutramigen. Pyroglutamic acid was detected and estimated by a variety of methods, and the merits of the techniques used and their application in a screening programme are discussed.

Glutamine-valine index - An aid in the detection of urea-cycle disorders.

By relating the increase in glutamine to the corresponding increase in valine following protein loading it has been possible to detect carriers of OCT deficiency.

Conditions affecting the colorimetry of orotic acid and orotidine in urine.

We studied conditions affecting a colorimetric assay of total orotic acid (orotic acid plus orotidine) in urine. Most interfering substances can be conveniently removed on a small column of cation-exchange resin, and an improved control reaction corrects for residual background color. Analytical recovery from urine is nearly complete (greater than 95%) and the absorption spectrum for analyte eluted from the column closely resembles that for an orotic acid standard. We determined reference intervals for total orotic acid, expressed as a molar ratio to creatinine, for neonates, children, and adults, and assessed the effect of age, protein intake, and pregnancy. The method is simple enough to use as a reliable and accurate urine-screening test.

Ginseng--is there a use in clinical medicine?

Panax ginseng occupies an important place among the tonic remedies of Oriental medicine. Pharmacological investigations show that crude ginsenosides can increase non-specific resistance of an organism to various untoward influences. The effects of purified derived derivatives have only recently become better studied in immunological and cell growth studies in animals and in man. This has now provided some evidence to suggest that ginseng is a drug that contains many derivatives with different pharmacological properties, which could be useful in clinical medicine.

In-vitro antibiotic inactivation by mammalian cell and killed bacterial preparations.

Inactivation of a range of antibiotics acting at different points in the metabolism of the bacterial cell was detected by estimating the MIC and MBC in the presence of liver and other tissue preparations. High temperature treatment and sonication of liver cells increased their ability to inactivate antibiotic action. This treatment would have almost completely destroyed enzyme activity, which was, therefore, not thought likely to be the cause of the phenomenon. The loss of antibiotic activity may be related to "protein binding" and a dialysis experiment showed that penicillin binding with liver homogenate was very much greater than with human albumin. It may be that increased disruption of tissue cells by physical methods exposes more active binding sites which reduces the bioavailability of antibiotics. Some degree of binding specificity was indicated in experiments in which DNA was shown to block antibiotics acting primarily on DNA--related synthesis and RNA blocked antibiotics acting on RNA--related metabolism. Suggestions are made for the cause of failure of antibiotic treatment in certain clinical situations.

Inhibition of bovine liver lysine-ketoglutarate reductase by urea cycle metabolites and saccharopine.

Lysine-ketoglutarate reductase was purified 675-fold from bovine liver mitochondria. Product inhibition studies gave results similar to those reported for this enzyme extracted from other sources. Inhibition studies with L-citrulline exhibited mixed inhibition patterns. No inhibition of the partially-purified enzyme by ammonium salts was detected; in contrast, marked inhibition of the enzyme by ammonium was apparently observed in crude liver homogenates. This was probably due to depletion of NADPH and/or 2-oxoglutarate in the assay mixture as a result of conversion of ammonium to glutamate by glutamate dehydrogenase. A similar explanation could account for the high levels of lysine observed in humans with urea cycle disorders.

Three instances of neonatal death with hyperammonaemia, each resulting from a different cause.

We report here the results of a study of three unrelated patients, K., M. and R., each of whom died in the neonatal period in St Sophia's Children's Hospital, Athens, Greece, after a normal pregnancy and delivery. Liver functions tests and blood cultures gave normal results in each case and autopsy did not reveal any specific findings. All had gross hyperammonaemia and were considered to have possible urea cycle defects.

Protein intake and plasma amino-acids of infants of low birth weight.

The plasma amino-acid levels in infants of low birth weight fed on expressed human milk and on a proprietary breast-milk substitute, S26, with a protein intake of not more than 4.5 g/kg/day were compared with those in infants fed on an evaporated milk formula whose protein intake ranged from 6.15 to 12.3 g/kg/day, as well as with normal infants on normal feeds and protein intake. In general, there was little difference between the levels in infants of low birth weight and in normal infants on the same protein intake. The five infants of low birth weight on high protein intake had generally higher levels of plasma amino-acids compared with the group on the lower protein intake, and in particular the levels of tyrosine, phenylalanine, methionine, and cystathionine could be extremely high. Apart from methionine these high levels may be the result both of a reduction in activity of the enzymes involved in the metabolism of these amino-acids, due to the immaturity of the infant, and of the increased stress of a high protein intake. In view of a possible long-term effect of abnormally high plasma amino-acid levels it is suggested that the protein intake of infants of low birth weight should not exceed 6 g/kg/day.

Neurological features and computed tomography of the brain in children with ornithine carbamoyl transferase deficiency.

The clinical features and the computed tomographic appearances of the brain in seven children with ornithine carbamoyl transferase deficiency are described. Episodic vomiting and drowsiness, acute encephalopathy, failure to thrive and developmental retardation were common, but focal neurological symptoms and signs were also observed. The CT appearances were non-specific with generalised or focal changes. They were related to the severity, the duration and the age of onset of the hyperammonaemia. Since the CT changes may suggest conditions other than metabolic disease, the emergency investigation of a child with an encephalopathy should include the estimation of plasma ammonium and, if elevated, the appropriate investigations to establish the cause.