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Biomedical subjects

R A Harkness

Publications and source records attributed to R A Harkness.

At least 37 records · Page 2Linked to original sources
PubMed1988

Antenatal fetal heart rate variation in relation to the respiratory and metabolic status of the compromised human fetus.

Three groups of women were delivered by caesarean section before labour: for an abnormal fetal heart rate (FHR) trace (21 cases, group 1), or for maternal deterioration in severe pre-eclampsia without gross fetal heart rate abnormalities (20 cases, group 2), or to avoid mechanical difficulties in labour at term (30 cases, group 3). The mean gestational ages of the first two groups were 32 weeks with a high proportion of infants small-for-gestational-age. In group 1, FHR variation (mean range of pulse intervals) was less than half (20.6 SE 1.2 ms) of the normal value at the same age (44.4 SE 1.5 ms). This was associated with hypoxaemia (mean umbilical artery PO2 of 6 mmHg at delivery), with evidence of compensation shown by an elevated amniotic fluid erythropoietin. The fetuses were hypoglycaemic and had greater umbilical artery blood alanine concentrations, but no large changes in adenine nucleotide or endorphin plasma concentrations. Although there was a minor degree of respiratory acidaemia at birth, there was not significant metabolic acidaemia. The results demonstrate that the reduced variation of 'suboptimal' and 'decelerative' fetal heart rate records is associated with fetal hypoxaemia and evidence of nutritional deprivation, but not with asphyxia.

Cesarean Section↗
PubMed1988

Clinical and biochemical assessments of damage due to perinatal asphyxia: a double blind trial of a quantitative method.

Using conventional criteria, a series of 26 infants was selected for intrapartum asphyxia from about 4000 deliveries over one year at a single hospital to assess the efficacy of a new biochemical method. Tissue damage was estimated from urinary excretion of hypoxanthine, an important and central intermediate in purine metabolism. The overall pattern showed agreement between the grading (by previously accepted methods) of asphyxia in the perinatal period and our new biochemical approach. The association with handicap at one year of age following asphyxia was complex. This biochemical technique could be used to exclude postasphyxial damage as a cause of clinical disturbances and to select a small group (0.1% of all births) who require further investigation for rarer disorders which may also cause long term handicap.

Asphyxia Neonatorum↗
PubMed1987

Lesch-Nyhan syndrome: growth delay, testicular atrophy and a partial failure of the 11 beta-hydroxylation of steroids.

There is a failure of growth in hypoxanthine guanine phosphoribosyltransferase deficiency; slow weight gain is marked after the second year of age but is apparent in the birth weights of all eight of our patients for whom we have data. However, head growth and bone development are less affected than weight. A partial defect in the adrenocortical 11 beta-hydroxylation of steroids was demonstrated after ACTH stimulation in all four patients studied. This hydroxylation takes place in mitochondria the function of which is modulated by purine nucleotide concentrations; this may be the link with the enzyme defect. Testicular atrophy at autopsy was found in two pubertal age boys and seven patients aged 12-17 years had no signs of puberty. All five boys aged 3-11 years showed less than the normal mean response of plasma testosterone concentration to human chorionic gonadotrophin despite the normal histological appearance of the testes of one 6-year-old-boy. Follicle stimulating hormone responses to gonadotrophin releasing hormone are probably less than in normal in at least three of the seven prepubertal boys. The absence of the normally high activities of hypoxanthine guanine phosphoribosyltransferase in testes appears to inhibit their ability to respond to gonadotrophin.

Adolescent↗
PubMed1987

Clinical biochemistry of the neonatal period: immaturity, hypoxia, and metabolic disease.

This review attempts to provide practical information on common problems in the laboratory medicine of newborn infants and also considers unresolved problems in achieving neonatal diagnoses. A common cause of upset in the newborn--intrapartum asphyxia--can now be positively diagnosed. This leaves a small group whom it is necessary to investigate because they may have metabolic disease. The initial investigation of metabolic disease at the district general hospital should be limited to the commoner conditions.

Adenosine Triphosphate↗
PubMed1984

ATP, ADP and AMP in plasma from peripheral venous blood.

ATP, ADP and AMP in concentrations at least 1 mumol/l have been found by high pressure liquid chromatography (HPLC) in plasma from peripheral venous blood. Total adenine nucleotide concentrations of about 15-20 mumol/l can be found in some conventional clinical samples of blood using EDTA as an anticoagulant. EDTA prevented adenine nucleotide conversion to inosine in plasma. In order to estimate concentrations in vivo, the contribution derived from the cell breakage inherent even in careful venous blood sampling has been estimated by extrapolation to zero 'haemoglobin' concentration in plasma and minimum values in samples of small volume. Available results appear to be consistent with the release of small amounts of ATP in or near the peripheral circulation at the time of venepuncture. In CSF, ATP, ADP and AMP concentrations were less than 0.05 mumol/l suggesting that membrane activity in the central nervous system is not associated with non-specific leakage. The high Km variant of lymphocyte ecto-5'-nucleotidase was not associated with a significantly higher concentration of its substrate AMP in plasma. However, this enzyme may function on the lymphocyte in the thymus and spleen.

5'-Nucleotidase↗
PubMed1983

Xanthine oxidase deficiency and 'Dalmatian' hypouricaemia: incidence and effect of exercise.

In order to study the effects of raising the hypoxanthine concentration in plasma on its metabolism and renal handling, the effects of intense exercise have been investigated in a patient with xanthine oxidase deficiency. Despite the 90-fold increased concentration of hypoxanthine in plasma above resting levels in normal individuals, the intracellular concentration of the initial product of hypoxanthine in cells, IMP, was unaffected. Evolution may have stabilized intracellular nucleotide concentrations against the large fluctuations in plasma hypoxanthine which occur during exercise. The renal handling of hypoxanthine is consistent with 'filtration'. In contrast, xanthine clearances may exceed those for creatinine and urinary concentrations do not correlate with those for creatinine; 'secretion' may be involved. Xanthine excretion may reflect guanine breakdown. A retrospective survey of urate concentrations in blood from 47 420 patients followed by further selected investigations detected 2 women with persistent marked hypouricaemia and high urinary urate clearances, 'Dalmatian' hypouricaemia. High pressure liquid chromatographic analysis of plasma extracts can distinguish xanthine oxidase deficiency from other causes of hypouricaemia.

Erythrocytes↗
PubMed1983

Changes in the electrophoretic pattern of salivary peroxidase at the middle of the menstrual cycle.

Salivary peroxidase activity is known to increase at the middle of the menstrual cycle, and we report changes in electrophoretic patterns of salivary peroxidase over the same period. Peroxidase during the early follicular and late luteal phases of the menstrual cycle has been resolved into three forms by polyacrylamide gel electrophoresis. An additional, low mobility peroxidase has been detected at midcycle when two electrophoretic forms occurring at other times are reduced; this is coincident with the peak in total peroxidase activity. Available evidence suggests that this ovulatory peroxidase represents a catalytically active aggregate of the peroxidases normally present in saliva.

Electrophoresis, Polyacrylamide Gel↗
PubMed1983

Purine transport and metabolism in man: the effect of exercise on concentrations of purine bases, nucleosides and nucleotides in plasma, urine, leucocytes and erythrocytes.

1. After decreasing muscle ATP by a 2 min period of intense exercise, we have studied purine metabolism by using high-pressure liquid chromatography. 2. A major increase in hypoxanthine concentration in plasma and urine was found with increases in xanthine and, in plasma, inosine. Erythrocyte hypoxanthine rose with the level in plasma, but there was no corresponding rise in IMP, the first intracellular metabolite of hypoxanthine. No rises in uridine or urate were found in plasma. 3. Plasma adenosine did not rise and fall significantly after exercise, but a small rise and fall in adenine nucleotide concentrations in plasma was found. 4. Running, swimming and games, which tended to be at the weekend, were associated with a rise in hypoxanthine and xanthine excretion; exercise was probably the cause of the higher excretion during the day than at night. Such activities do not produce changes in concentrations of ATP in muscle, although turnover must rise. 5. The results are consistent with widespread purine exchange between tissues and a 'circulating hypoxanthine pool'.

Adult↗
PubMed1983

Effect of two antibiotics on human granulocyte activities.

As part of a study of the effects of antibiotic therapy upon human phagocytes, ampicillin and cefaclor were each administered orally to nine healthy adult subjects in a single dose of 500 mg. There was a significant difference in their effects on neutrophil myeloperoxidase (MPO) (EC.1.11.1.7) activity (P less than 0.05) in that ampicillin depressed, but cefaclor enhanced, the measured enzyme activity. Concomitantly ampicillin decreased but cefaclor increased, the rate of phagocytosis of staphylococci, the effects of the two antibiotics also being significantly different (P less than 0.05). Direct measurements of intracellular killing of staphylococci did not change. In four patients with chronic bacterial infections who had low levels of neutrophil MPO activity, treatment with cefaclor led to a significant increase in the MPO levels to within the normal range. Three patients responded satisfactorily to cefaclor despite having previously filed to respond to antibiotics which were similarly active in vitro against the causative bacteria. These findings lead us to suggest that, in patients with chronic refractory infections, attention must be given to the effect of drugs on the host defences in addition to a careful choice of the most active antibacterial agent.

Adult↗
PubMed1983

Ratio of the concentration of hypoxanthine to creatinine in urine from newborn infants: a possible indicator for the metabolic damage due to hypoxia.

The ratio of the urinary concentrations of the ATP metabolite, hypoxanthine, to that of creatinine was determined in normal newborn infants. An increase in this ratio reflects high hypoxanthine excretion and thus ATP breakdown. The ratio can be determined on random urine samples, thus simplifying sampling. Urinary changes are persistent; abnormalities are detectable on the second day of life after intrapartum hypoxia. Preliminary results suggest that this ratio on a sample during the second day of life could 'diagnose' intrapartum hypoxia and might therefore quantitatively assess those obstetric 'risk factors' believed to operate through hypoxia.

Creatinine↗
PubMed1983

Concentrations of hypoxanthine, xanthine, uridine and urate in amniotic fluid at caesarean section and the association of raised levels with prenatal risk factors and fetal distress.

Samples of amniotic fluid were obtained at caesarean section from 33 of 80 consecutive unselected patients in whom the membranes were intact. Concentrations of the ATP metabolites, hypoxanthine and xanthine, as well as uridine and urate were determined using high pressure liquid chromatography. Independent 'clinical' factors associated with reduced fetal growth and well-being were identified and the patients were assigned to one of three groups: those with no recognized risk, those with moderate risk and a small group of four patients with high risk. The mean hypoxanthine concentration was higher in the moderate-risk group than in the group with no risk. Two of the three patients with proteinuric hypertension in the high-risk group had normal hypoxanthine concentrations. There were seven patients with fetal distress, and concentrations of hypoxanthine, xanthine, uridine and urate were significantly higher in the three patients who had meconium stained amniotic fluid in addition to abnormal fetal heart rate tracings than in the remaining four who had fetal heart rate abnormalities only. It is suggested that fetal distress at emergency caesarean sections might be quantitated by such analysis.

Amniotic Fluid↗
PubMed1983

Cerebrospinal fluid concentrations of hypoxanthine, xanthine, uridine and inosine: high concentrations of the ATP metabolite, hypoxanthine, after hypoxia.

CSF obtained for clinical purposes from newborn, children and adults has been analysed by high pressure liquid chromatography for hypoxanthine, xanthine, inosine, uridine and urate. Large rises in hypoxanthine and to a lesser extent xanthine occur for about 24 h after hypoxia. High concentrations were associated with later evidence of brain damage or subsequent death. Changes in CSF could be independent of those in plasma. Small or negligible rises were associated with localised and generalised infections including bacterial meningitis, fits, or both. Marked and rapid rises were found after death. These estimations may "predict" the extent of brain damage or brain death.

Adult↗