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Biomedical subjects

W Oh

Publications and source records attributed to W Oh.

At least 127 records · Page 7Linked to original sources

Effects of chronic fetal hyperinsulinemia on plasma arachidonic acid and prostaglandin concentrations.

In adult diabetic subjects and infants of diabetic mothers, hyperglycemia has been associated with increased intravascular thromboxane and decreased prostacyclin production. Because of the association between states of altered insulin concentration and prostaglandin metabolism, we hypothesized that chronic experimentally induced fetal hyperinsulinemia results in perturbations in fetal arachidonic acid and prostaglandin metabolism. Arachidonic acid, thromboxane B2 (the stable breakdown product of thromboxane A2), and 6-keto-prostaglandin F1 alpha (the stable breakdown product of prostacyclin) were determined in the arterial blood of chronically catheterized fetal sheep after 9 to 12 days of continuous insulin (15 U.day-1, n = 7) or placebo (n = 5) infusion. Fetal insulin infusion resulted in fetal hypoglycemia and a reduction in fetal arterial plasma arachidonic acid concentration (p less than 0.01). In addition, the concentration of thromboxane B2 relative to 6-keto-prostaglandin F1 alpha was significantly reduced in the insulin-treated group compared with the placebo-treated group (p less than 0.03). We conclude that fetal hyperinsulinemia in sheep produces perturbations in prostaglandin metabolism with reductions in the plasma arachidonic acid concentration and in the plasma concentration of thromboxane A2 relative to prostacyclin. The hyperinsulinemic-hypoglycemic state in the fetus influences the relative proportion of the vasoconstricting to the vasodilating prostaglandins, thereby potentially modulating fetal vasomotor tone.

6-Ketoprostaglandin F1 alpha↗

Behavioral characteristics and early temperament of premature infants with intracranial hemorrhage.

Behavioral characteristics of 12 full-term and 44 premature infants with and without intracranial hemorrhage (ICH) were studied. Cranial ultrasonography prospectively documented Grade I-II ICH in 14, Grade III-IV in 19 and no ICH in 11 premature infants. Examination at corrected age of 40 +/- 2 weeks using the Neonatal Behavioral Assessment Scale showed that infants in the ICH groups had lower levels of arousal and more abnormal reflexes than full-terms. Infants with ICH III-IV displayed less optimal motor responses than full-term infants and diminished orientation responses, especially to visual stimuli. Thus, lower level of arousal, immature motoric processes, and poor visual orientation differentiated premature with ICH from full-term infants, although premature infants without these sequelae, did not differ significantly from full-term infants. The above may represent early manifestations of visual-perceptual and motor problems noted in the follow-up of ICH infants. Further, neonatal behavior was found to affect parent ratings of infant temperament (via the Bates Infant Characteristics Questionnaire) at 3 months corrected age, and the relationships between neonatal behavior and parental ratings differed depending upon the infant's gestational age and severity of hemorrhage. We conclude that neonatal behaviors are less optimal in premature infants, and least optimal in premature infants with severe intracranial hemorrhage when compared to fullterm infants.

Arousal↗

Neurologic and developmental status related to the evolution of visual-motor abnormalities from birth to 2 years of age in preterm infants with intraventricular hemorrhage.

We prospectively and longitudinally evaluated neurologic status, cognitive status, and visual-evoked responses in 63 premature infants with cerebral intraventricular hemorrhage, 27 premature infants without hemorrhage, and 22 full-term normal infants. We hypothesized that severe intraventricular hemorrhage (grades III and IV) is associated with impaired visual-motor function, in part because of compression-related injury of the periventricular white matter by ventricular dilation. Infants with grade III or IV hemorrhage had significantly more neurologic sequelae at term and at 3, 7, 12, and 24 months; lower Bayley mental and motor scores at 3, 7, and 12 months; more abnormality on Kohen-Raz subscales for eye-hand coordination, object manipulation, and object relations at 3, 7, and 12 months; and lower Mullen vision-receptive and vision-expressive coordination scores at 24 months. The 12-month visual-evoked response correlated with the 24-month vision-receptive and vision-expressive organization scores for infants with grade III or IV intraventricular hemorrhage (r = -0.49, p less than 0.01, and r = -0.40, p less than 0.05, respectively). The data confirm our hypotheses of increased cognitive and neurologic sequelae, and increased abnormality of visual-motor coordination, during the first 2 years of life in infants with severe (grade III or IV) intraventricular hemorrhage.

Cerebral Hemorrhage↗

Abnormal brain-stem function (brain-stem auditory evoked response) correlates with acoustic cry features in term infants with hyperbilirubinemia.

We hypothesized that changes in brain-stem auditory evoked responses related to bilirubin would be associated with changes in cry because of the anatomic proximity in the brain stem of cranial nerves 8 (auditory) and 9 to 12 (vagal complex, which controls cry). Brain-stem auditory evoked responses and computerized cry analysis were used to study the concurrent effects of moderate hyperbilirubinemia on auditory function and cry. Fifty term infants were divided equally into two groups on the basis of serum bilirubin concentrations: low (less than 8 mg/dl; 136) mumol/L and moderate (10 to 20 mg/dl, 170 to 342 mumol/L). Forty-three infants had successful tracings of brain-stem auditory evoked responses recorded with a Cadwell model 5200A evoked response unit during two successive trials, and a cry recording of each infant was analyzed by computer. The moderate serum bilirubin group had an increase in percent cry phonation (p less than 0.02) and an increase in the variability of the first formant (p less than 0.04) in comparison with the low serum bilirubin group. Serum bilirubin values correlated positively with brain-stem conduction time (r = 0.36, p less than 0.01), percent phonation (r = 0.42, p less than 0.004), and variability of the first formant (r = 0.39, p less than 0.02). Percent phonation, the voiced component produced by increased neural control, correlated with the interpeak of waves latencies I to III (r = 0.32, p less than 0.03) and brain-stem conduction time (wave I to V) (r = 0.35, p less than 0.01). We conclude that hyperbilirubinemia affects adjoining areas of the brain stem that control hearing and cry production.

Brain Stem↗

Effects of intravenous glucose loading on oxygen consumption, carbon dioxide production, and resting energy expenditure in infants with bronchopulmonary dysplasia.

To determine the effects of intravenous glucose loading on basal oxygen consumption, resting energy expenditure, and basal carbon dioxide production in infants with bronchopulmonary dysplasia who were still oxygen dependent, we administered intravenous glucose loads of 4 and 12 mg/kg-1/min-1 on 2 consecutive days, under identical experimental conditions, to six infants with bronchopulmonary dysplasia and six healthy control subjects. Infants were not fed for 9 hours before and during the 4- to 6-hour study periods; the intravenous glucose infusion, along with an amino acid mixture (2 gm.kg-1.24 hr-1), was started at the beginning of the fasting period. Oxygen consumption and carbon dioxide production and resting energy expenditure were measured by a flow-through indirect calorimetry technique under basal conditions. Infants with oxygen-dependent bronchopulmonary dysplasia had significantly higher basal oxygen consumption and resting energy expenditure than did control infants and significantly higher basal carbon dioxide production during the high glucose infusion. With glucose loading, infants with bronchopulmonary dysplasia had a significant rise in basal oxygen consumption (7.91 +/- 0.91 ml.kg-1.min-1 to 9.65 +/- 1.35 ml.kg-1.min-1, p less than 0.05), basal carbon dioxide production (5.93 +/- 0.72 ml.kg-1.min-1 to 7.10 +/- 1.04 ml.kg-1.min-1), and resting energy expenditure (53.8 +/- 5.75 kcal.kg-1.24 hr-1 to 65.3 +/- 7.0 kcal.kg-1.24 hr-1, all p values less than 0.05). Control infants had no significant changes with intravenous glucose loading. We conclude that intravenous glucose loading in infants with bronchopulmonary dysplasia resulted in a net increase in resting energy expenditure, which should be taken into account in assessing their energy intake during nutritional management. The risk of pulmonary stress caused by an increase in basal oxygen consumption and carbon dioxide production resulting from glucose load should also be considered.

Bronchopulmonary Dysplasia↗

Language and neurodevelopmental outcome of low-birthweight infants at three years.

Forty low-birthweight (LBW) infants (28 AGA, 12 SGA) and 16 fullterm infants have been followed for three years with neurological, developmental, language, behavior and audiometric assessments. Only two (5 per cent) of the LBW infants were neurologically abnormal at three years. The AGA infants continued to lag cognitively and in receptive language in comparison with the fullterm infants. Socio-economic factors had a significant effect on the language development of all three groups. Short gestation and neurological status at eight months continued to have a significant effect on language performance. A variety of behavioral characteristics correlated with cognitive and language scores, and impaired middle-ear status was associated with lower cognitive function. These data support the concept that language development of LBW infants is influenced by perinatal, neurological and socio-economic factors, and by behavioral characteristics and middle-ear status.

Child Behavior↗

Postprandial gastrointestinal blood flow and oxygen consumption during environmental cold stress.

We studied the independent and combined effects of feeding and environmental cold stress by measuring pre- and postprandial gastrointestinal blood flow (QGI), oxygen consumption (GIVO2), and oxygen extraction (GIO2ex) in seven awake 3- to 4-day-old piglets while in a thermoneutral environment (control phase, 31 degrees C) and during environmental cold stress (experimental phase, 20.5 degrees C). Each animal consecutively completed both the control and experimental phases. In the control phase, measurements were made before and 30 min after feeding. In the experimental phase, measurements were made before and 30 min after induction of cold stress. A feeding was then given and measurements repeated 30 min later during continued cold stress. QGI (ml.100 g-1.min-1) increased postprandially while in a thermoneutral environment (130 +/- 11 to 152 +/- 12) but not while in a cold environment (126 +/- 15 to 121 +/- 8). Postprandial GIVO2 (ml O2.100 g-1.min-1) increased from 2.1 +/- 0.2 to 3.7 +/- 0.5 while in a warm environment. During preprandial cold stress, an unexpected increase in GIVO2 was observed (1.7 +/- 0.2 to 3.1 +/- 0.5). Feeding while in a cold environment provoked a further significant increase in GIVO2 (3.1 +/- 0.5 to 4.2 +/- 0.4). All increases in GIVO2 were associated with increased GIO2ex. This study has demonstrated that 1) postprandial GIVO2 is appropriately increased during cold stress as a function of GIO2ex and 2) that fasting GIVO2 is increased during cold stress, demonstrating an intestinal metabolic contribution to cold-induced systemic thermogenesis.

Animals↗

Effects of prolonged hyperinsulinemia on erythropoiesis in fetal sheep.

Offspring of diabetic mothers have an increased incidence of neonatal polycythemia, decreased oxygen tension in cord blood at delivery, and elevated plasma erythropoietin levels at birth. Experimental fetal hyperinsulinemia has been associated with reduced fetal oxygen content and increased erythropoietin concentration. To test the hypothesis that prolonged fetal hyperinsulinemia results in increased fetal erythropoiesis and red cell volume during gestation, we infused insulin or placebo for 11 +/- 0.2 (+/- SE) days into chronically catheterized fetal sheep, beginning at 124 days of gestation. Indices of fetal erythropoiesis, red cell and blood volume were measured before and during the infusions. Insulin infusion resulted in increased plasma insulin, decreased plasma glucose, and decreased oxygen saturation values. The nucleated red blood cell (RBC) and RBC counts were significantly higher in the insulin- compared with the placebo-treated fetal sheep after 6-8 and 9-12 days of infusion, respectively. Although erythropoietin concentration did not differ between the groups, red cell volume expressed as a change from the base-line value was significantly higher in the insulin-treated group. We conclude that prolonged fetal hyperinsulinemia augmented erythropoiesis and red cell volume during late gestation in fetal sheep.

Animals↗

Permeability of the blood brain barrier for 125I-albumin-bound bilirubin in newborn piglets.

Permeability of the blood brain barrier (BBB) for bilirubin and 125I-albumin was studied in 2-d- and 2-wk-old piglets. 125I-albumin was given by bolus at the beginning of each study. Hyperbilirubinemia was produced by an initial bolus infusion of bilirubin and sustained at a plasma bilirubin:albumin molar ratio of approximately 1.0 by continuous infusion of bilirubin for 3 h. During the study period, arterial pH and blood gas tensions, serum osmolarity, and mean arterial blood pressure were within the physiologic range for age in both groups. Serum albumin and serum total and unbound bilirubin concentrations were higher in the 2-wk-old piglets. Brain bilirubin concentrations and permeability (P.S product) of the BBB for bilirubin were higher in the 2-d-old than in the 2-wk-old piglets, but the values of P.S for albumin were not different between the two groups. In 2-d-old piglets, regional brain bilirubin concentrations and permeability of the BBB were higher in subcortical regions (cerebellum and brainstem) than in the cerebral cortex. Regional brain albumin concentrations and BBB permeability to albumin in 2-d-old piglets were higher only in the cerebellum. In all regions, the bilirubin:albumin molar ratio was higher in the brain tissues than in the blood. In 2-wk-old piglets, the brain concentrations and P.S products for bilirubin were lower and the regional differences were less marked than for 2-d-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Neonatal sympathoadrenal response to acute hypoxia: impairment after experimental intrauterine growth retardation.

Sympathoadrenal system function may be altered following intrauterine growth retardation (IUGR). We tested the hypothesis that the growth-retarded newborn rat pup has increased basal sympathoadrenal activity under normoxic conditions and a blunted sympathoadrenal response to acute hypoxia. IUGR was established by uterine artery ligation on d 18 of gestation in Sprague-Dawley rats. Growth-retarded pups were chosen as those whose birth wt was more than 2 x SD below the mean birth wt of control pups delivered to sham-operated dams. At 24 +/- 12 h of age cardiac sympathetic neuronal activity (CSNA) was determined by 3H-norepinephrine tracer and alpha-methyltyrosine techniques. Adrenal medullary catecholamine synthesis (CAT SYN) was measured by 14C-tyrosine precursor methods, and adrenal catecholamine release (CAT REL) was determined using alpha-methyl-tyrosine. IUGR and control pups were studied over a 120-min period of normoxia or hypoxia (FiO2 = 0.09). Under normoxic conditions, the IUGR pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to controls. Adrenal CAT REL in normoxic IUGR pups was selective for epinephrine. In response to acute hypoxia, control pups had increased CSNA and increased adrenal CAT SYN and CAT REL compared to normoxic controls, with the proportion of norepinephrine and epinephrine released mimicking the ratio of the two amines in the adrenal. In contrast, in hypoxic IUGR pups CSNA and adrenal CAT SYN did not increase, and norepinephrine alone was released from the adrenal medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Plasma catecholamine concentrations of newborn piglets in thermoneutral and cold environments.

Plasma epinephrine and norepinephrine concentrations were measured in seventeen unanaesthetized 3 to 4 days-old piglets while in a thermoneutral environment (31.3 degrees C) and 30, 45 and 60 min after induction of environmental cold stress (19.9-23.1 degrees C). Plasma epinephrine and norepinephrine concentrations in a warm environment were 142 +/- 26 pg/ml, and 456 +/- 44 pg/ml respectively. Environmental cold stress evoked significant increases in norepinephrine values after 30 (624 +/- 58 pg/ml), 45 (626 +/- 60 pg/ml) and 60 (626 +/- 54 pg/ml) min of cold stress. Plasma epinephrine concentrations did not significantly change during environmental cold stress. Post-hoc stratification of piglets into normothermic (deep rectal temperature 38.6 degrees C-38.8 degrees C, n = 9) and hypothermic (deep rectal temperature 37.1 degrees C-37.7 degrees C, n = 7) subgroups revealed significant increases in plasma norepinephrine concentrations only in the hypothermic subgroup. We conclude that plasma norepinephrine, but not epinephrine, is increased in newborn piglets during environmental cold stress and that the changes in norepinephrine concentrations are related to body core hypothermia. We speculate that hypothermia-mediated reductions in peripheral norepinephrine breakdown and re-uptake contribute to the rise in circulating levels.

Animals↗

Gastrointestinal blood flow and oxygen delivery during environmental cold stress: effect of anaemia.

We studied the effect of environmental cold stress with and without isovolaemic anaemia on blood flow and oxygen delivery to the stomach, small intestine, and colon. The purpose of the study was to investigate the independent and combined effects of an increased oxygen demand (cold stress) and decreased oxygen availability (anaemia). Six, 3-4 days-old, awake piglets having normal haematocrit (26%), were studied in a warm environment (31.7 +/- 0.4 degrees C) and 30 min after reaching the nadir of cold stress (19.9 +/- 0.4 degrees C). Subsequently, a warm environment was reestablished and a partial volume, plasma exchange transfusion was done to lower the haematocrit to approximately 15%. Piglets were then studied as before in warm (32 +/- 0.5 degrees C) and cold (19.3 +/- 0.3 degrees C) environments. In the non-anaemic study phase, cold stress provoked a decrease in blood flow (ml.100g-1.min-1) to the small intestine (226 +/- 22 vs. 134 +/- 22) while oxygen delivery (ml O2.100g-1.min-1) was decreased to the stomach (13.6 +/- 1.4 vs 9.3 +/- 1.7), small intestine (19.6 +/- 0.6 vs. 11.2 +/- 1.1) and colon (9.6 +/- 1.7 vs. 6.1 +/- 1.0). Following plasma exchange transfusion (anaemic study phase), warm environment values for gastrointestinal blood flow did not differ from non-anaemic warm environment values. However, mean oxygen delivery while in a warm environment was decreased to the stomach (-45%), small intestine (-49%) and colon (-42%). Among anaemic piglets, cold stress provoked a further decrease in oxygen delivery to the small intestine (9.9 +/- 1.2 vs. 6.5 +/- 0.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Pulmonary oxygen toxicity in the guinea pig. Effect of indomethacin.

Deleterious pulmonary effects of hyperoxia are thought, in part, to be mediated by high-energy radicals and inflammatory reactions. It has been suggested that arachidonate metabolites, such as leukotrienes, may be responsible for the latter mechanism. We sought to demonstrate that concurrent exposure to hyperoxia and indomethacin, a potent inhibitor of cyclooxygenase, would increase pulmonary inflammation. A total of 50 female guinea pigs were treated as pairs with 95.6% oxygen or air and separately with 0.3 mg/kg of indomethacin or normal saline every 12 h for 3 days. A significant increase in leukocytes in bronchopulmonary lavage subsequent to combined oxygen and indomethacin treatment was observed when compared with either oxygen, indomethacin, or air treatments alone (p less than 0.05). Although oxygen treatment did alter pulmonary volume-pressure relations (p less than 0.05), hyperoxia alone or with concurrent indomethacin treatment did not alter elastance or histologic structures. These findings suggest that pulmonary inflammation in response to hyperoxia may be augmented by indomethacin. We speculate that increased lipoxygenase products of arachidonate metabolism may be partially responsible for these changes.

Animals↗

Mothers of preterm and full-term infants on home apnea monitors.

We prospectively studied the stress perception of ten mothers of preterm infants on apnea monitors (birth weight, 1255 +/- 295 g) and ten mothers of term infants on monitors (3156 +/- 700 g) and compared them with 15 mothers of preterm infants (1450 +/- 305 g) and 15 mothers of term infants (3360 +/- 595 g) not on monitors. The Life Experience Survey, a stress assessment questionnaire, and the social support questionnaire of Henderson were administered to the 50 mothers. Stress perception scores were higher for mothers of infants on monitors than for mothers of infants not on monitors. Regression analyses indicated that mothers of infants on monitors experienced less perceived stress when they received greater support. Mothers of infants on monitors who experienced less stress reported greater general life satisfaction and greater satisfaction with parenting.

Adult↗

Maternal hyperglycemia in pregnant rats: its effect on growth and carbohydrate metabolism in the offspring.

Mild hyperglycemia during the last half of pregnancy was achieved by administration of streptozotocin to pregnant rats on the fifth day of gestation. Citrate buffer (vehicle for streptozotocin) was administered to control rats also on the fifth day of gestation. The pups born to the streptozotocin-treated mothers had higher birth weight, pancreatic insulin content, plasma insulin, and C-peptide concentrations compared with pups born to control mothers. The plasma glucose concentrations of the pups were similar between the two groups. The pups who were identified as macrosomic (birth weight greater than 1.7 SD than the mean of the control pups) maintained an accelerated postnatal growth through the first 10 weeks of age in female rats and in the first 3, and at 5 and 6 weeks of age for the male rats. The accelerated growth in the female rats was associated with higher perirenal-ovarian and salpingeal fat weight at 6 weeks. At 10 weeks of age, higher plasma insulin and glucose concentrations were observed following oral glucose challenge in both male and female macrosomic rats than in the control rats. At 12 weeks of age, only the female macrosomic rats showed abnormal glucose response due to peripheral insulin resistance. In the male rats at 12 weeks of age, a higher plasma insulin concentration in the macrosomic group was associated with a normal plasma glucose response to oral glucose challenge. We conclude that mild maternal hyperglycemia in rats resulted in fetal hyperinsulinemia and accelerated fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗