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Biomedical subjects

R Hume

Publications and source records attributed to R Hume.

At least 127 records · Page 7Linked to original sources

Studies on the relationship between glutathione S-transferase phenotype and bile acid binding by human liver cytosol.

The possibility that the GST1 phenotype of human liver cytosol is a determinant of bile salt binding has been investigated by using equilibrium dialysis and gel-exclusion chromatography. Binding of bile salts was non-saturable and whereas the glutathione S-transferases did not appear to be major bile salt binders, other binding components with molecular weights of 35 000 and 11 000 were identified in both fetal and adult cytosols.

Adult↗

Prevention of subglottic stenosis in neonatal ventilation.

Mechanical ventilation of the newborn is now widely used in neonatal intensive care. The oro-tracheal route of intubation is simpler, but for long-term ventilation has been considered unstable. A method of fixation of oro-tracheal tubes is described which overcomes this instability. Five hundred consecutive ventilated infants were intubated by the oro-tracheal route and the tube was fixed by the method described. Of the 500 ventilated infants, 213 died without being extubated. Of the 287 survivors, 44 developed a degree of post-extubation stridor. No surviving infant developed clinical evidence of subglottic stenosis and in almost 200 postmortem examinations laryngeal narrowing was not identified. The method of oro-tracheal fixation described is stable and may reduce the incidence of subglottic stenosis.

Beclomethasone↗

Food iron and lead absorption in humans.

Food iron and lead absorption were measured simultaneously in 28 subjects by extrinsically labeling three consecutive meals with the radioactive tracers, iron 59-sulfate and lead 203-chloride. Absorption was measured directly in all subjects by whole-body counting and indirectly in 15 subjects by assessing subsequent levels of tracer in blood. Iron status of the subjects ranged from iron deficient to replete, thus providing a wide range of iron absorption. Statistically significant positive correlations were obtained between food-iron and lead absorption measured by whole-body counting and also between the tracer levels of iron and lead in the blood. However, the correlation between the absorption of the two elements was not strong, as evidenced by the fact that only 50% of the subjects who hyperabsorbed iron also hyperabsorbed lead.

Administration, Oral↗

Nasogastric compared with nasoduodenal feeding in low birthweight infants.

One hundred successive infants weighing less than 1500 g at birth were allocated alternately to intermittent nasogastric or continuous nasoduodenal feeding regimens. Eighty were appropriate for gestational age, and of these 25 fed successfully by nasogastric tube and 16 tolerated nasoduodenal feeding until 1600 g. No significant differences in either calorie intake or growth rates were identified throughout the seven weeks of the study. Because of the increased complexity and radiological exposure involved with feeding transpylorically, nasogastric feeding may be preferred as a method of feeding the low birthweight infant.

Enteral Nutrition↗

The human glutathione S-transferases: developmental aspects of the GST1, GST2, and GST3 loci.

The expression of the GST1, GST2, and GST3 loci in fetal, neonatal, and infant tissues has been studied using starch gel electrophoresis and chromatofocusing. Each locus demonstrated developmental changes in expression, some of which were specific to a single tissue while others occurred in several tissues. GST1 was not usually expressed in any of the tissues studied before 30 weeks of gestation but steadily increased thereafter until adult levels were reached in late infancy. In neonates and older infants the frequencies of the GST1*0, GST1*1, and GST1*2 alleles were 0.79, 0.07, and 0.14, respectively. GST2 was always expressed in liver and adrenal but was only weakly expressed in spleen, cardiac muscle, and diaphragm. In kidney this locus was not usually expressed until nearly 1 year after birth. The GST3 isoenzymes were present in all fetal, neonatal, and infant tissues, although their expression in liver decreased after 30 weeks of gestation. Other isoenzymes with fast anodal mobilities were also identified in several tissues; these are believed to be GST3 isoenzymes that have undergone posttranslational modification rather than products of the putative GST4 locus. No specifically fetal isoenzymes were detected.

Chromatography↗

Rickets of prematurity: calcium and phosphorus supplementation.

Seventy-four infants weighing less than 1500 gm at birth were fed enterally from birth until day 47. Group A (18 infants) were given SMA Gold Cap: group B (18 infants), supplementary calcium to 21 mmol/L (84 mg/dl); group C (16 infants), further calcium supplementation to 31.2 mmol/L (125 mg/dl); and group D (22 infants), milk with calcium content 31.2 mmol/L (125 mg/dl) and phosphorus supplementation to 15.7 mmol/L (49 mg/dl). The addition of calcium reduced the radiologic evidence of rickets, and combined calcium and phosphorus supplementation maintained plasma alkaline phosphatase activity within the normal range for 6 weeks.

Alkaline Phosphatase↗

Endocrine studies in cyanotic congenital heart disease.

Seven male patients with cyanotic congenital heart disease were studied. Serum testosterone, androstenedione, dehydroepiandrosterone, thyroxine and triiodothyronine levels did not differ significantly from control values. Thyroid stimulating hormone and prolactin responses to injected thyrotrophin releasing hormone were normal. Impaired gonadotrophin responses to injected gonadotrophin releasing hormone were noted in two patients. The hypothalmic-pituitary-testicular axis appears to be better preserved in cyanotic congenital heart disease than in chronic obstructive airways disease and restrictive lung disease for a similar degree of hypoxia. Possible explanations are discussed.

Adolescent↗

Measuring bile-salt concentrations lacks clinical value for detecting hepatic dysfunction in infants receiving parenteral nutrition.

Concentrations of conjugated cholate, chenodeoxycholate, direct bilirubin, and alanine aminotransferase (ALT, EC 2.6.1.2) were measured in plasma of 122 low-birthweight infants receiving parenteral nutrition. Eighteen (15%) of them developed hepatic dysfunction. We observed two distinct biochemical patterns in these infants. In the Type A pattern (12 infants), concentrations of direct-reading bilirubin and bile salts increased with no change in ALT activity. In the Type B pattern (six infants), increases in the concentrations of bile salt and direct bilirubin were followed by increases in ALT activity. Hepatic dysfunction persisted significantly longer in infants who developed the Type B pattern. The two patterns did not differ significantly in the times at which values for bile salts or direct bilirubin in plasma became abnormal or became normal at resolution, nor did maximal concentrations of bile salts in plasma differ significantly. Maximal concentrations of direct bilirubin were higher in the Type B infants. We conclude that, in such infants, measurement of bile-salt concentrations in plasma offers no advantages for detecting hepatic dysfunction over the more conventional measurement of direct bilirubin in plasma.

Alanine Transaminase↗

The catalytic cycle of cytochrome P-450scc and intermediates in the conversion of cholesterol to pregnenolone.

Cytochrome P-450scc as isolated is a cholesterol-depleted low-spin haemoprotein; addition of cholesterol results in formation of a high-spin complex. Cytochrome P-450scc--cholesterol is a one-electron acceptor on titration with NADPH. Cytochrome P-450scc--cholesterol can be anaerobically reduced to the ferrous state which, on oxygenation, forms an oxygenated cytochrome P-450scc--cholesterol complex. This oxygenated complex in the absence of adrenodoxin autoxidises to ferric cytochrome P-450scc--cholesterol without oxidation of cholesterol. The decay of the oxygenated complex is first-order, k = 9.3 X 10(-3) S-1 at 4 degrees C. The rate of autoxidation is influenced by pH, ionic strength and the chemical nature of bound sterol. The activation energy of autoxidation is 75 kJ mol-1. Addition of equimolar amounts of adrenodoxin to cytochrome P-450scc--cholesterol followed by stoichiometric reduction under anaerobic conditions and subsequent oxygenation, allows single catalytic turnover cycles of cytochrome P-450scc to be observed. This has led to detection of intermediates in the conversion of cholesterol to pregnenolone and a precursor/product sequence of cholesterol----22-hydroxycholesterol----20,22-dihydroxy-cholesterol ----pregnenolone has been established. Addition of oxidised adrenodoxin to oxygenated cytochrome P-450scc--cholesterol results in formation of 22-hydroxycholesterol.

Adrenal Cortex↗

The human glutathione S-transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes.

Three sets of isozymes of glutathione-S-transferase (GST) have been identified in human tissues. They differ in their tissue distribution, incidence of genetic variation, susceptibility to inactivation by N-ethylmaleimide and in their electrophoretic mobilities. The GST1 isozymes exhibit four phenotypes, including a common 'null' phenotype attributable to different combinations of three autosomal alleles GST1 1, GST1 2 and GST1 0 of frequency 0.13, 0.23 and 0.64, respectively, in the European population. The genetic polymorphism of GST1 is easily demonstrable in adult liver, kidney, adrenal and stomach but the isozymes are only weakly expressed in skeletal and cardiac muscle and not at all in fetal liver, fibroblasts, erythrocytes, lymphocytes and platelets. The GST2 isozymes also exhibit variant patterns but these are probably due to post-synthetic modification rather than allelic variation. The GST2 isozymes are not detectable in erythrocytes, platelets, cultured fibroblasts or lymphocytoid cells but are found in many other tissues, including fetal liver. GST3 isozymes were found as relatively strong components in every tissue examined except adult liver, with slight tissue to tissue variability in electrophoretic mobility.

Adrenal Glands↗

Parenteral nutrition compared with transpyloric feeding.

Fifty nine infants of birthweight less than 1500 g were allocated alternately to initial total parenteral nutrition or to transpyloric feeding. Mortality was similar between the two groups. Ten of the 29 infants in the transpyloric group failed to establish full enteral nutrition during the first week of life. No beneficial effects on growth were shown in infants receiving parenteral nutrition. Acquired bacterial infection was higher in the parenteral group and associated with morbidity and mortality. Conjugated hyperbilirubinaemia occurred only in the parenterally fed infants. The incidence of necrotising enterocolitis was higher in the transpyloric group. Parenteral nutrition does not confer any appreciable benefit and because of greater complexity and higher risk of complications should be reserved for those infants in whom enteral feeding is impossible.

Body Weight↗

The effect of ascorbic acid on the seasonal variations in serum cholesterol levels.

One gram of ascorbic acid (Vitamin C) administered randomly to a group of healthy young people (aged 29 +/- 5 years) produced a significant mean fall in serum cholesterol of 16 per cent within two months. A similar supplement to a group of healthy older people (aged 58 +/- 3 years) produced a significant mean fall in serum cholesterol of 14 per cent but required six to 12 months' administration. Serial observations on a mixed age group of healthy people (aged 38 +/- 12 years) over one calendar year revealed a seasonal fluctuation in serum cholesterol, the lowest levels being in summer (June 5.5 +/- 0.7 mmols/l) and the highest levels in winter (January 6.4 +/- 0.8 mmols/l), a significant rise of 16 per cent. These changes showed an inverse relationship with the leucocyte and serum ascorbic acid levels which also revealed a seasonal fluctuation, the months April/September being higher than the months October/March. The administration of 1g of ascorbic acid per day throughout the year abolished the winter rise in serum cholesterol levels. These results are discussed in the light of the relationship between cholesterol and vascular disease and the observations by Sir Richard Doll that lowering the cholesterol level, whether achieved by drugs or diet, results in a reduction in morbidity from myocardial infarction.

Adult↗

Klebsiella infection in a neonatal intensive care unit.

Fourteen infants in a Neonatal Intensive Care Unit became colonized with Klebsiella pneumoniae. Ten developed septicaemia. All infants survived the acute infection. Details are given of clinical observations and the control measures that were taken.

Disease Outbreaks↗

Polymorphonuclear leucocyte transfusion in neonatal septicaemia.

In one neonatal intensive care unit during a 15 month period 6 infants developed septicaemia which was resistant to antibiotic treatment. The infants' mean gestational age and birthweight were 32.7 weeks and 1519 g respectively. Intravenous infusions of polymorphonuclear leucocytes were given. Three infants died and the remainder survived without complications. No side effects of the treatment were identified.

Anti-Bacterial Agents↗