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Biomedical subjects

P A Auld

Publications and source records attributed to P A Auld.

At least 19 recordsLinked to original sources
PubMed1992

Ascorbic acid prevents oxidative stress in glutathione-deficient mice: effects on lung type 2 cell lamellar bodies, lung surfactant, and skeletal muscle.

Glutathione deficiency in adult mice leads to lung type 2 cell lamellar body and mitochondrial damage; as reported here, these effects are associated with marked decrease of the levels of phosphatidylcholine (the main component of lung surfactant) in the lung and the bronchoalveolar lining fluid. Severe mitochondrial damage was also found in skeletal muscle. Treatment with ascorbate (1-2 mmol per kg of body weight per day), which led to greatly increased (approximately 2-fold) levels of lung and muscle mitochondrial glutathione, prevented damage to lamellar bodies and mitochondria as well as the decline of phosphatidylcholine levels in lung and alveolar lining fluid. The findings indicate that glutathione deficiency leads to depletion of lung surfactant and that this can be prevented with ascorbate. Administration of ascorbate spares glutathione and prevents cellular damage. Lamellar body degeneration in glutathione deficiency appears to be associated with oxidative damage to the perilamellar membrane, which contains the enzymes required for phosphatidylcholine synthesis. It is notable that although severe glutathione deficiency is lethal to newborn rats, which apparently do not synthesize ascorbate, adult mice are better able to survive such a deficiency because they can synthesize ascorbate. The present studies, which suggest that high doses of ascorbate may be of therapeutic value, emphasize that ascorbate and glutathione have actions in common and that they function together in a physiologically significant antioxidant system.

Animals↗
PubMed1992

Hand preference, prematurity and developmental outcome at school age.

Information was obtained on the hand preference of 88 premature and 80 matched full-term children at 7-8 years old. These children were also evaluated for neurologic status, IQ, attention-deficit hyperactivity disorder, and learning disabilities. Although the difference on hand preference was not significant, 12% more of the premature children than the full-term children were left- or mixed-handed. Results showed that, among premature children, there is an association between non-right-handedness and cognitive and behavioral deficits and that left-handed children show relative clumsiness with the non-preferred hand.

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress.

A model for oxidative stress is described in which glutathione (GSH) synthesis is selectively blocked in newborn rats by administration of L-buthionine-(S,R)-sulfoximine (BSO). In this model, the normal endogenous physiological formation of reactive oxygen species is largely unopposed, and therefore oxidative tissue damage occurs; because GSH is used for reduction of dehydroascorbate, tissue ascorbate levels decrease. In lung there are decreased numbers of lamellar bodies and decrease of intraalveolar surfactant. Proximal renal tubular, hepatic, and brain damage also occur. A diastereoisomer of BSO that does not inhibit GSH synthesis, L-buthionine-R-sulfoximine, does not produce toxicity; this control experiment renders it unlikely that the observed effects of BSO are produced by the sulfoximine moiety itself. There is correlation between the decrease of mitochondrial GSH levels and mitochondrial and cell damage. Oxidative stress as evaluated by mitochondrial damage and mortality can be prevented by treatment with GSH esters or ascorbate. There is apparent linkage between the antioxidant actions of GSH and ascorbate. This model, which may readily be applied to evaluation of the efficacy of other compounds in preventing oxidative stress, offers an approach to study of other effects of GSH deficiency (e.g., on lipid metabolism, hematopoiesis), and closely resembles oxidative stress that occurs in certain human newborns and in other clinical states.

Aging↗
PubMed1991

Glutathione deficiency leads to mitochondrial damage in brain.

Glutathione deficiency induced in newborn rats by giving buthionine sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase, led to markedly decreased cerebral cortex glutathione levels and striking enlargement and degeneration of the mitochondria. These effects were prevented by giving glutathione monoethyl ester, which relieved the glutathione deficiency, but such effects were not prevented by giving glutathione, indicating that glutathione is not appreciably taken up by the cerebral cortex. Some of the oxygen used by mitochondria is known to be converted to hydrogen peroxide. We suggest that in glutathione deficiency, hydrogen peroxide accumulates and damages mitochondria. Glutathione, thus, has an essential function in mitochondria under normal physiological conditions. Observations on turnover and utilization of brain glutathione in newborn, preweaning, and adult rats show that (i) some glutathione turns over rapidly (t 1/2, approximately 30 min in adults, approximately 8 min in newborns), (ii) several pools of glutathione probably exist, and (iii) brain utilizes plasma glutathione, probably by gamma-glutamyl transpeptidase-initiated pathways that account for some, but not all, of the turnover; thus, there is recovery or transport of cysteine moieties. These studies provide an animal model for the human diseases involving glutathione deficiency and are relevant to oxidative phenomena that occur in the newborn.

Aging↗
PubMed1991

Aortic root blood flow increases after pancuronium in neonates with hyaline membrane disease.

OBJECTIVE: To determine the effects of muscle paralysis on aortic root blood flow in preterm infants with hyaline membrane disease. DESIGN: Each patient served as his/her own control in a prospectively controlled trial. SETTING: Neonatal ICU in a university hospital. PATIENTS: Ten ventilator-dependent preterm infants weighing 800 to 2820 g, 0 to 8 days of age, with hyaline membrane disease and seven control patients. INTERVENTIONS: Noninvasive measurement of aortic root blood flow by Doppler echocardiography 30 min before and 60 min after respiratory paralysis with 0.1 to 0.5 mg/kg of iv pancuronium, or following ventilator changes in control subjects. RESULTS: Mean aortic root blood flow increased significantly (p less than .001), from 212 to 276 mL/min.kg, accompanied by significant increases in stroke volume and heart rate. CONCLUSIONS: Pancuronium bromide may have a direct beneficial effect on the circulation of preterm infants with hyaline membrane disease.

Aorta↗
PubMed1991

Acute shift in immune response to microbial activators in very-low-birth-weight infants.

Investigation of lymphocyte activation in vitro to microbial pathogens was undertaken in very-low-birth-weight infants during the first 2 weeks of life. Twenty-three infants with birth weights less than 1500 g were studied on day 1. Normal adults (n = 23) and cord blood from seven full-term infants were used as controls. Longitudinal studies were also carried out on seven of the 23 infants 2 weeks following delivery. Results indicated that lymphocyte responses of very-low-birth-weight infants on day 1 of life were significantly greater than those of both adult controls and full-term infants, particularly to Haemophilus influenzae, Staphylococcus epidermidis and Staphylococcal protein A. In contrast, response to the T cell mitogen phytohaemagglutinin (PHA) was significantly less in very-low-birth-weight infants than in adult controls and full-term infants. The seven very-low-birth-weight infants studied showed a down-regulation of immune response in the 2 weeks following birth, such that responses on day 14 were significantly less than those on day 1 for the same activators. This shift in immune response appears to have important implications for the immune development and host defence in the post-natal period.

Bacteria↗
PubMed1991

Educational status and school-related abilities of very low birth weight premature children.

Eighty-eight premature children with birth weights less than or equal to 1500 g were evaluated at ages between 7 and 8 years old to determine their academic status in comparison with those of a matched full-term group. Results showed that a much higher proportion of the premature children required special educational interventions (48%) than either the full-term children (15%) or the New York State public elementary school population (10%). More than half of the premature children who received educational intervention were neurologically impaired or had below normal intelligence. The entire group of premature children differed significantly from the matched full-term group on IQ score and on tests of verbal ability, school achievement, and auditory memory. Lower socioeconomic status children performed significantly less well on each type of these measures and on a measure of attention than children of the higher socioeconomic status group. There was an interaction of prematurity and social class on Full Scale IQ, verbal tests, academic achievement, and attention, with lower socioeconomic status premature children scoring lowest on these measures. The subset of premature children normal in both IQ and neurologic status did not differ significantly from a matched normal full-term group on any cognitive measures other than arithmetic ability, but they continued to have significantly lower academic achievement scores.

Cerebral Palsy↗
PubMed1990

Ventilation-perfusion abnormalities in the preterm infant with hyaline membrane disease: a two-compartment model of the neonatal lung.

Arterial-alveolar differences for oxygen, carbon dioxide, and nitrogen were measured in 7 non-distressed preterm infants and 21 ventilator-dependent preterm infants with hyaline membrane disease. The preterm infants with hyaline membrane disease had a significantly lower average arterial pH (7.34 vs. 7.44; P less than 0.001), and significantly higher arterial-alveolar differences for oxygen (286 mm Hg vs. 34 mm Hg; P less than 0.005) and nitrogen (118 mm Hg vs. 7 mm Hg; P less than 0.005). Both groups had elevated arterial-alveolar differences for PCO2 (9 mm Hg in infants with hyaline membrane disease, 5 mm Hg in nondistressed infants; P less than 0.2). When acute changes in mean airway pressure were produced in 14 distressed infants, arterial-alveolar CO2 and N2 differences moved in opposite directions in 11 infants. This observation suggests that changes in mean airway pressure do not acutely recruit atelectatic alveoli, but cause redistribution of ventilation within alveoli already ventilated.

Carbon Dioxide↗
PubMed1990

Survival and outcome of infants weighing less than 800 grams at birth.

This study reports on two aspects of outcome in a sample of infants whose birth weights ranged from 500 to 799 gm. First, maternal and early neonatal variables were analyzed by means of stepwise logistic regression. Five-minute Apgar score and initial pH were the only variables that predicted mortality at p less than or equal to 0.05. Second, the surviving infants were examined at ages ranging from 17 months to 7 years. The majority (72%) had neurologic and/or developmental examinations in the suspect or abnormal range and required rehabilitation or early intervention services.

Body Constitution↗
PubMed1990

Social competence and behavior problems in premature children at school age.

Social competence and behavior problems of 87 children born weighing less than 1501 g were measured using the Child Behavior Checklist when the children were 7 to 8 years old. Both premature boys and girls had significantly lower Social Competence scores than the normative samples of their respective sexes. Only premature boys had significantly higher Behavior Problems scores, with significantly higher scores on behaviors associated with conduct disorders. Premature children in each of three social class groups had significantly lower Social Competence scores and higher Behavior Problems scores than normative children. Furthermore, there was an interaction between prematurity and social class on Behavior Problems scores, with the greatest discrepancy in scores between premature and normative children in the lower-class group. Relative to other predictors, IQ score best explained Social Competence scores and family stability best explained Behavior Problems scores in the premature sample.

Child↗
PubMed1989

Pulmonary function in preterm infants following treatment with intravenous indomethacin.

Pulmonary function tests, including measurements of arterial blood gas levels, total pulmonary compliance, and arterial-alveolar oxygen ratios, were performed in 38 ventilator-dependent preterm infants with respiratory distress syndrome who weighed less than 1500 g at birth. Twenty-seven had a physiologically significant patent ductus arteriosus (PDA). Twelve were assigned at random to receive three doses of intravenous indomethacin, 0.2 mg/kg per dose, on the fourth day of life. This treatment resulted in ductal closure in seven infants by the seventh day of life. Another concurrently observed group of 15 infants with PDA received no indomethacin. A third group of 11 infants lacked evidence of a PDA. Pulmonary function in the infants who received indomethacin did not differ significantly from that in the other two groups.

Ductus Arteriosus, Patent↗
PubMed1989

Discrepancies between transcutaneous and end-tidal carbon dioxide monitoring in the critically ill neonate with respiratory distress syndrome.

PaCO2, transcutaneous PCO2 (PtcCO2), and end-tidal PCO2 (PetCO2) measurements were studied in 12 critically ill neonates. PtcCO2 was measured using a combination CO2/O2 sensor during the routine care of these patients. End-tidal sidestream sampling was performed during blood gas measurement as dictated by the patient's clinical condition. There was a linear correlation between PtcCO2 and PaCO2 (n = 51, r = .71, slope = 0.90). PetCO2 and PaCO2 did not correlate as well (n = 51, r = .52, slope = 0.42). Acidosis negatively affected the correlation between PtcCO2 and PaCO2. When pH was greater than 7.30, r = .75 and slope = 1.28 (n = 38), whereas when pH was less than 7.30, r = .62 and slope = 0.73 (n = 13). The presence or absence of a metabolic acidosis did not have a significant effect on the slopes obtained. PtcCO2 monitoring using combined sensors is a useful and practical means of monitoring in the neonatal ICU, although acidosis affects the ability to correlate transcutaneous and arterial values. End-tidal sidestream measurements are not as clinically useful because they vary due to different ventilation/perfusion relationships in the sick neonate.

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

Hand preference of four-year-old children: its relationship to premature birth and neurodevelopmental outcome.

Information was obtained at age four years on the hand preference of 98 children who had been born prematurely with a very low birthweight and of 54 children born at term with no birth complications. Data were also collected on the hand preference of their parents. The preterm children had been assessed at age three years for IQ, expressive language, speech articulation and neurological status. A significantly lower proportion of preterm than of term children used their right hand for unimanual activities. Furthermore, those preterm children who were not right-handed were significantly more likely to have lower IQs, expressive language delays and articulation problems. Among preterm children with IQs greater than or equal to 85, language and speech problems were no more likely to occur in those who preferred the left hand or who used both hands than in those who preferred the right. The findings of this study support the theory that birth complications lead to cerebral insult which may alter hand preference, and at the same time affect mental and motor development.

Child Development↗
PubMed1986

Early predictors of neurodevelopmental outcome of very low-birthweight infants at three years.

Seventy-nine premature infants weighting less than 1501 g at birth but appropriate for gestational age underwent a neurodevelopmental examination at one, three, six, nine and 12 months post-term, and a standard neurological examination and the Stanford-Binet Intelligence Scale at three to four years of age. Children were classified as normal, suspect or abnormal on the three-year neurological examination, on the IQ test, and on composite neurodevelopmental outcome at age three years. Results showed that items from both the nine- and 12-month neurodevelopmental examinations correctly classified about 80 per cent of the children as to composite outcome at three years. In addition, the 12-month examination enabled correct prediction for 89 per cent of the children as to neurological outcome and for 82 per cent as to IQ. Neurodevelopmental examination of high-risk infants in the last quarter of the first year of life (post-term) should assist pediatricians in predicting which children will be normal and which will require early intervention.

Cerebral Palsy↗
PubMed1986

Early predictors of one-year outcome for infants asphyxiated at birth.

This study attempted to identify within the first 48 hours of life those infants sustaining hypoxic-ischemic insults and destined to have neurodevelopmental abnormalities at one year of age. Neurological examination and cranial CT scan were quantitated to provide a post-asphyxia score and CT low-density index for each of 34 fullterm infants. The post-asphyxia score and CT infarction index were used to predict infants with normal and abnormal outcomes at one year of age, and both were valuable predictors of neurodevelopmental sequelae.

Asphyxia Neonatorum↗
PubMed1986

Insulin pump therapy in the very low birth weight infant.

Ten critically ill, very low birth weight infants less than 30 weeks' gestation were treated with exogenous insulin administered through a continuous insulin infusion pump (Betatron II, Cardiac Pacemaker, Inc). Infants were hyperglycemic to dextrose infusions greater than 6 mg/kg/min. The blood glucose concentration became normal in all infants within two to four hours, with varying requirements for continued insulin treatment. Tolerance to intravenous dextrose increased from a mean of 7.4 mg/kg/min to 11.2 mg/kg/min with glycosuria. Energy intake increased from 49.5 calories/kg/d prior to insulin pump therapy to 70.4 calories/kg/d afterward (P less than .01) with weight gain changed from -23 g/d to +13 g/d (P less than .01). One unexpected observation was the apparent normalization of blood glucose homeostasis on higher dextrose doses among some infants after only one three- to six-hour treatment with insulin. The continuous insulin infusion pump is a flexible tool that allows insulin infusion rates to be changed as dictated by blood glucose values without altering other parenteral infusions.

Acute Disease↗