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Biomedical subjects

R A Harkness

Publications and source records attributed to R A Harkness.

At least 55 records · Page 3Linked to original sources
PubMed1982

Intrapartum hypoxia: the association between neurological assessment of damage and abnormal excretion of ATP metabolites.

A series of 29 newborn infants had been studied after intrapartum hypoxia defined as meconium aspiration, an Apgar score of less than or equal to 6 at 5 min or a peripheral blood pH of 7.2 or less after resuscitation. Two independent sets of techniques were used; one concerned with the critical system in hypoxic damage, the central nervous system, the other assessing the central biochemical events in hypoxia. Both sets of data were assembled, then graded separately and only then combined. In this way detailed neurological assessment has been combined with measurement of urinary excretion of the ATP metabolites, hypoxanthine and xanthine. The essential metabolic consequence of hypoxia is a reduction in the synthesis of the energy currency of cells, ATP. This is associated with an outflow of ATP metabolites from cells. The extent of neurological damage was related to the magnitude of the hypoxanthine and xanthine excretion; neither were closely related to the initial blood pH. Infants who were normal neurologically had normal oxypurine excretion. Infants with neurological abnormalities for less than 48 h had lower excretion than those who were abnormal for more than 48 h. The duration of abnormal oxypurine excretion after an acute episode of hypoxia was studied in two infants with respiratory distress and in two other infants with apnoeic attacks. Severe hypoxia was followed by abnormal oxypurine excretion for at least 40 h after an acute episode. It is justifiable to suggest that abnormalities of oxypurine excretion should indicate intrapartum hypoxia in newborn infants. This excretion should also quantify the metabolic damage.

Adenosine Triphosphate↗
PubMed1982

Activities of enzymes involved in purine metabolism and some related adenine nucleotide concentrations of leucocytes in renal failure.

We have studied purine metabolism in mononuclear and polymorphonuclear cells from uraemic patients using microradiochemical enzyme assays and high-pressure liquid chromatography. In mononuclear cell lysates the mean activities of adenosine deaminase (EC 3.5.4.4) and 5'-nucleotidase (EC 3.1.3.5) were significantly diminished. The activities of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), adenine phosphoribosyltransferase (EC 2.4.2.7), and hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were not significantly different in the two groups. The activities of adenosine deaminase and adenine phosphoribosyltransferase were reduced in the polymorphonuclear cell lysates. No clear differences emerged in the concentration of adenine nucleotides in the mononuclear cells. The significance of these changes, which are less marked than those in erythrocytes, is discussed with reference to the immunodeficiency associated with uraemia.

Adenine Nucleotides↗
PubMed1981

High-performance liquid chromatographic methods for base and nucleoside analysis in extracellular fluids and in cells.

High-performance liquid chromatography based methods for the study of the metabolism of purine and pyrimidine bases and nucleosides have been developed. These methods, using 200--50 microliter samples of extracellular fluids and employing isocratic separations, can measure a wide range of compounds. Hypoxanthine, xanthine and uridine concentrations in plasma from normal men are relatively stable. Species differences have been detected: concentrations of cytidine are higher in rat and mouse serum than in man, since the concentrations of uridine are similar; purine/pyrimidine ratios may be different. Fetal calf serum used for tissue culture contains about a 40 times higher concentration of hypoxanthine than the less-effective calf serum. Use of the methods appears to be justified in the assessment of the metabolic damage due to severe hypoxia and/or ischaemia.

Animals↗
PubMed1981

Effect of renal failure on erythrocyte purine nucleotide, nucleoside and base concentrations and some related enzyme activities.

1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes. 2. The mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant elevations of adenylate kinase (EC 2.7.4.3), purine nucleoside phosphorylase (EC 2.4.2.1), hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and adenosine deaminase (EC 3.5.4.4) but not of adenine phosphoribosyltransferase (EC 2.4.2.7) and ribosephosphate pyrophosphokinase (phosphoribosylpyrophosphate synthetase; EC 2.7.6.1) activities were demonstrated. However, there was an overlap between results from patients with renal failure and normal (control) subjects. Erythrocyte phosphoribosylpyrophosphate levels were also unchanged. 3. Erythrocyte nucleotide concentrations especially those of inosine were raised in renal failure. 4. The plasma inosine was reduced in renal failure. 5. The significance of these changes is discussed.

Adolescent↗
PubMed1981

Raised hypoxanthine, xanthine and uridine concentrations in meconium stained amniotic fluid and during labour.

Amniotic fluid samples were obtained at induction of labour in 64 women; in 15 of these there was meconium staining of the amniotic fluid; the remainder showed no signs of fetal distress. Using high pressure liquid chromatography, compared to the samples from normal patients there were highly significantly raised levels of hypoxanthine, xanthine and uridine in the meconium stained samples; oxypurines in the meconium itself could not explain the difference. Where serial samples were obtained during labour by intrauterine catheter, a terminal rise in oxypurine levels was apparent. Where the proportion of oxypurine present as hypoxanthine exceeded one per cent in amniotic fluid at the time of induction, there was a significantly greater occurrence of late fetal heart rate decelerations in the ensuing labour. These findings are consistent with other evidence that when tissues become hypoxic the metabolic products of nucleotide breakdown escape from the cells and appear in extracellular fluid. Oxygen lack in the fetus probably causes loss of these compounds from the hypoxic kidneys to the urine so that they appear in amniotic fluid.

Amniotic Fluid↗
PubMed1981

The measurement of hypoxanthine, xanthine, inosine and uridine in umbilical cord blood and fetal scalp blood samples as a measure of fetal hypoxia.

Hypoxanthine, xanthine, inosine, urate and uridine, were measured in 149 samples of umbilical cord plasma using high pressure liquid chromatography. In spite of a good correlation with the simpler oxygen consumption method for measuring hypoxanthine, there was no clear discrimination between hypoxic and well oxygenated infants, although mean concentrations were higher in infants with well defined criteria of intrapartum hypoxia or bith asphyxia, there was overlap with the normal range. Fetal scalp blood samples were also found to be clinically unhelpful in the diagnosis of intrapartum hypoxia, at least in part due to variable degrees of haemolysis in the specimens. There were poor correlations between hypoxanthine concentrations and those of hydrogen ion, base deficit and lactate. Uridine concentrations were significantly higher in arterial cord blood than in venous cord blood but hypoxanthine or xanthine concentrations did not show this difference.

Female↗
PubMed1981

Neonatal spongioform myelinopathy after restricted application of hexachlorophane skin disinfectant.

At least four out of 97 low birth weight (less than 1750 g) newborn infants who had received only limited skin disinfection with 3% hexachlorophane (HCP) emulsion developed spongioform myelinopathy in association with detectable amounts of HCP in their brains. These four cases were found in a post-mortem survey of 20 out of the 27 infants who died. Another nine of these infants had detectable amounts of HCP in the brain but no myelinopathy. It is at present not possible to define a 'safe" level of exposure to 3% HCP emulsion for small preterm infants in the first 2 weeks of life.

Brain↗
PubMed1980

Is inosine the physiological energy source of pig erythrocytes?

Pig erythrocytes are unable to metabolize glucose and their physiological energy source is unknown. These cells have a high-capacity nucleoside transport system with similar properties to that responsible for nucleoside transport in other species. Nucleoside transport is sufficiently rapid to allow the possibility that inosine and/or adenosine may represent major energy substrates for pig erythrocytes in vivo. Normal and adenosine deaminase-deficient pig erythrocytes have similar ATP levels, suggesting that adenosine is not important in this respect. However, it was calculated that an extracellular inosine concentration of only 40 nM could support the cells' entire energy requirement, a value 40-fold lower than plasma levels of this nucleoside.

Adenosine Deaminase↗
PubMed1980

Neutral 17beta-hydroxysteroid oxidoreductase deficiency in testes causing male pseudohermaphroditism in an infant.

A deficiency of neutral 17beta-hydroxysteroid oxidoreductase activity in testes has been diagnosed in a n infant with male pseudohermaphroditism. In vivo stimulation tests of testicular endocrine function with human chorionic gonadotrophin provided an accurate diagnosis in contrast to estimates of enzymic activity in vitro in testes and other tissues. The discrepancy in testes may be due to the absence of gonadotrophin stimulation in the latter studies. The in vitro studies show that there are at least two forms of 17beta-hydroxysteroid oxidoreductase under independent genetic control and that only one form is localized to the testes. The diagnosis before puberty has allowed early treatment by removal of the abnormal testes which should prevent the usual presenting clinical signs of marked masculinizatin and hirsutism at puberty.

17-Hydroxysteroid Dehydrogenases↗
PubMed1980

The causes of low oestrogen excretion in pregnancy: the development of diagnostic methods for the antenatal detection of familial congenital adrenocortical hypoplasia.

A pregnancy producing a boy with congeital adrenocortical hypoplasia is described. Consistently low oestrogen excretion, less than 10 umol/24 h, was not associated with any anatomical abnormality or diminished growth of the fetus as judged by ultrasound examination. Fetoplacental steroid sulphatase definciency was excluded by finding normal maternal excretion of oestrogen precursors, the 3Beta-hydroxy-5-ene steroid sulphates. Generalized adrenocortical hypoplasia was proven in the baby boy by analysis of steroid netabolites excreted in his urine. He suffered from salt loss and progressive jaundice. Both were responsive to gluco- and mineralo-corticoid replacement therapy. It is suggested that amniocentesis may be required for the antenatal diagnosis of congenital adrenocortical hypoplasia.

Adrenal Cortex Hormones↗
PubMed1980

Cot deaths in Edinburgh: infant feeding and socioeconomic factors.

One hundred and twenty-six consecutive cases of sudden infant death syndrome (SIDS) in the Edinburgh area have been studied with particular reference to the interrelationship of feeding, associated biochemical changes, and social status. There was an excess of cases born to parents in Social Classes IV and V: the effect was maximal in children who dies beyond 12 weeks of age. A low-grade uraemia was discovered in approximately one-fifth of the cases; analysis showed this to be related most strongly to bottle-feeding. Feeding habits were found to be associated with social class and this accounted for the relationship between bottle-feeding and the youth of mothers and also for an apparent relationship between uraemia in the infant and social class of the mother. Mothers of SIDS children were younger than expected and SIDS was found to be electrolyte imbalance is common in SIDS cases, nor did the findings support the suggestion that cross-infection due to overcrowding is an important aetiological factor. The significant factors of young motherhood, low social status, bottle-feeding, and mild uraemia in the babies are interrelated and seem to focus attention on unwitting 'mothering problems'. It is, however, not easy to see how this, or any other hypothesis, can account for all cases of SIDS.

Age Factors↗