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Biomedical subjects

W Oh

Publications and source records attributed to W Oh.

At least 91 records · Page 5Linked to original sources

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

Cerebral Hemorrhage↗

The oral motor development of low-birth-weight infants who underwent orotracheal intubation during the neonatal period.

OBJECTIVE: To investigate the potential development of oral motor problems following prolonged orotracheal intubation in low-birth-weight infants. DESIGN: Prospective observational. SETTING: Tertiary-care hospital. PATIENTS: Fifty-one low-birth-weight infants and 10 full-term infants divided into three groups--group 1 with 15 low-birth-weight infants (< or = 1250 g) who had been intubated for more than 1 week; group 2 with 36 low-birth-weight infants who had been intubated for 1 week or less; and group 3 with 10 full-term control infants. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Oral motor assessments of nutritive sucking were compared at corrected ages of term and 3 months. The results showed that low-birth-weight infants with prolonged intubation had significantly poorer sucking abilities at both term and 3 months. The number of days of oxygen use and the postnatal age (weeks) at which nipple feeding was begun were the most powerful predictors of sucking ability at term (P < .001), whereas the number of days of orotracheal intubation and gestational age at birth were the most powerful predictors of sucking ability at 3 months (P < .001).

Apgar Score↗

Prognostic value of clinical and radiological status on day 28 of life for subsequent course in very low birthweight (< 1,500g) babies with bronchopulmonary dysplasia.

To test the hypothesis that the short-term (approximately 6 months) course of babies with bronchopulmonary dysplasia (BPD) could be predicted from the clinical and radiological status on day 28 of life, we retrospectively examined the medical records of 79 infants born between 1985 and 1988 who required supplemental oxygen and/or ventilatory support on day 28. Chest roentgenographs taken close to day 28 (+/- 7 days) were scored on a scale of 0-10. Four babies died from causes not related to BPD. Four of the remaining 75 died from BPD, and the rest are alive. Forty-six of 71 were weaned from supplementary oxygen by 37 weeks corrected gestational age, and only 13/71 remained on supplemental oxygen after 40 weeks gestational age. To determine which variables contributed most to the outcome, defined as total days on supplemental oxygen, a multiple regression analysis was performed, including only those variables the tolerance of which exceeded 0.7 (sex, FiO2, ventilatory mode, and infectious status). FiO2 and ventilatory mode together predicted 15% of the variability in outcome, so that a high FiO2 and ventilator dependence on day 28 of life were highly correlated with a prolonged need for supplemental oxygen (F = 4.28, P < 0.05).

Bronchopulmonary Dysplasia↗

Mitogen-independent DNA synthesis by fetal rat hepatocytes in primary culture.

We have identified conditions under which late gestation fetal rat hepatocytes in primary culture proliferate in the absence of serum, polypeptide growth factors, or insulin. Fetal hepatocytes, cultured in defined minimal essential medium (MEM) with hydrocortisone, synthesized DNA within the first 6 h after plating and for up to 72 h. Rates of thymidine incorporation into DNA by fetal hepatocytes exceeded peak rates seen with adult rat hepatocytes. The latter were quiescent following isolation, with DNA synthesis only occurring after 48 h exposure to insulin plus epidermal growth factor. Although they exhibited a high rate of DNA synthesis, the fetal hepatocytes retained sensitivity to added mitogens; DNA synthesis was stimulated three- to fourfold by subnanomolar concentrations of TGF-alpha. Fetal hepatocytes also were sensitive to the growth inhibitory effects of TGF-beta at concentrations below 10 pM. Finally, ontogenic changes in serum- and mitogen-independent fetal hepatocyte growth were observed, with declining rates of DNA synthesis as term approached. We speculate that the ability of fetal rat hepatocytes to synthesize DNA independent of added serum or mitogens may coincide with a proliferative in vivo phenotype.

Animals↗

A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. DESIGN: Multicenter randomized trial. SETTING: Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. PATIENTS: Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. INTERVENTIONS: Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308). MAIN OUTCOME MEASURES: The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment. RESULTS: Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration. CONCLUSION: We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.

Biological Products↗

Breast-feeding of very low birth weight infants.

Twenty very low birth weight infants (birth weight < 1500 gm) were assessed to compare the clinical effects of breast and bottle feedings. The infants started breast-feeding during the same week that they started bottle feedings. Five breast-feedings and five bottle feedings for each infant were observed. Axillary temperature and weight before and after feedings were measured, and oxygen saturation, respiratory rate, and heart rate were monitored and recorded every 2 minutes during the feeding periods. The results showed no difference in oxygen saturation during breast-feeding (p = 0.056) but a lower incidence of oxygen desaturation (< 90%) (21% vs 38% in breast-feeding vs bottle feeding, respectively; p < 0.025). Infants with bronchopulmonary dysplasia had higher oxygen saturation during breast-feeding than during bottle feeding (p < 0.025), but weight gain during breast-feeding sessions was less (median, no gain vs 31 gm, p < 0.001). We conclude that (1) very low birth weight infants can tolerate both breast and bottle feedings at the same postnatal age; (2) very low birth weight infants are less likely to have oxygen desaturation to less than 90% during breast-feeding; and (3) weight gain is less during breast-feeding, probably because of lower intake, and may require more lactation counseling or supplementation of the feedings.

Body Weight↗

Growth and neurodevelopmental outcome of very low birth weight infants with intrauterine growth retardation: comparison with control subjects matched by birth weight and gestational age.

Eighty-one very low birth weight (VLBW) infants were followed for 3 years to assess the relative impact of intrauterine growth retardation on growth and development; 27 small for gestational age (SGA) infants were compared with 27 gestation-matched infants with appropriate size for gestational age (AGA) and 27 birth weight-matched AGA infants. It was hypothesized that growth and neurodevelopmental outcomes in SGA VLBW infants are poorer than those of AGA gestation-matched (AGA-GA) infants but do not differ from those of birth weight-matched (AGA-BW) control infants. Gestational ages of the SGA, AGA-GA, and AGA-BW infants were 29 +/- 2, 29 +/- 1, 26 +/- 2 weeks, and birth weights were 821 +/- 178, 1124 +/- 85, and 848 +/- 141 gm, respectively. The SGA infants did not differ from the AGA infants in neonatal course, but AGA weight-matched infants had lower Apgar scores and more days of assisted ventilation, and an increased incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, and seizures. At 3 years of age the SGA VLBW infants had lower weight and height than both comparison groups (p < 0.05). Neurologic outcome in SGA infants did not differ from that in AGA-GA infants. The AGA-BW infants had an increased incidence of suspect or abnormal neurologic findings at 2 and 3 years of age (p < 0.05). The SGA infants scored lower on developmental tests at 1, 2, and 3 years than AGA-GA infants but had scores similar to those of the AGA-BW group. We conclude that intrauterine growth retardation in VLBW infants has a significant long-term impact on growth. Although 3-year development of SGA infants is significantly lower than that of gestation-matched control infants, it does not differ from that of weight-matched control infants.

Birth Weight↗

Effects of birth order, gender, and intrauterine growth retardation on the outcome of very low birth weight in twins.

We hypothesized that gender and intrauterine growth retardation (IUGR) have greater effects than birth order on mortality and morbidity rates of very low birth weight (< 1501 gm) twins. Neonatal data were collected on 44 pairs of twins born alive between January 1984 and December 1987. Birth weight was 1018 +/- 289 gm and gestational age was 28.1 +/- 2.5 weeks. The male/female ratio was 46:42; 24 infants had IUGR, and 64 were appropriate in size for gestational age. Of the 88 infants, 61 (69%) survived. Birth order had no effect on outcome. Female twin pairs had a longer gestation than either male twin pairs or twins with discordant sex (29.2 +/- 2.5 weeks vs 27.4 +/- 2.0 weeks and 27 +/- 3 weeks, respectively; p < 0.002). They also had a lower mortality rate (14% vs 47% and 25%; p < 0.001) and a lower incidence of bronchopulmonary dysplasia (22% vs 57% and 50%; p < 0.02). Infants with IUGR had an increased mortality rate (50% vs 23%; p < 0.02) and an increased sepsis rate (61% vs 25%; p < 0.02) compared with infants with appropriate size for gestational age who were matched for gestational age. Multiple logistic regression analysis to assess the independent effects of gestational age, gender, and IUGR on mortality rate, bronchopulmonary dysplasia, and intraventricular hemorrhage revealed that gestational age was the most significant contributor to all three outcome variables; IUGR contributed to an increased mortality rate, and male gender contributed to the occurrence of bronchopulmonary dysplasia.

Apgar Score↗

Effect of intrauterine growth retardation on postnatal weight change in preterm infants.

To investigate the cause or causes of early postnatal weight change, we measured total body water and fluid and energy balances in 14 preterm infants who were appropriate in size for gestational age (AGA) and in 5 weight-matched, preterm, small-for-gestational-age (SGA) infants. On the first day of life, AGA and SGA infants had the same weight and total body water content. At 6 +/- 2 days (mean +/- SD), AGA infants had had significant weight loss (94 +/- 45 gm) and body water loss (67 +/- 80 ml), whereas weight and total body water content in the SGA infants at the same age (5 +/- 1 days) did not differ from the values at birth. Loss of weight and total body water in AGA infants was accompanied by a greater diuresis than in SGA infants at the same amount of fluid intake. At the end of week 1, AGA and SGA infants had the same total energy expenditure (184 +/- 33 vs 171 +/- 17 kJ.kg-1 x day-1); energy intake, which had exceeded total energy expenditure from the third day of life and beyond, already provided 188 +/- 46 (AGA) or 209 +/- 109 kJ.kg-1 x day-1 (SGA), respectively, for energy storage. Nitrogen balance was positive. Subsequent weight gain occurred at the same rate in AGA and SGA infants; both total body water and solids increased. Energy intake, total energy expenditure, and the amount of energy stored (measured during stable weight gain on a regimen of full enteral feedings) had significantly increased compared with week 1, but both groups maintained similar energy storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

Possible association between fluoxetine hydrochloride and colic in an infant.

This is a case study of a 6-week-old infant referred for colic whose mother was using fluoxetine hydrochloride and breast feeding the infant. The mother switched to a commercial formula and reported a dramatic decrease in the infant's crying. We asked the mother to feed the infant breast milk from a bottle and she agreed. Throughout the study the mother kept a daily diary of her infant's crying, sleeping, stooling patterns, and feeding problems. Analysis of the mother's breast milk showed concentrations of 69 ng/mL for fluoxetine and 90 ng/mL for norfluoxetine. Infant blood serum/plasma level was analyzed for fluoxetine hydrochloride following return to breast milk. The concentrations were 340 ng/mL for fluoxetine and 208 ng/mL for norfluoxetine. The diary records showed increased crying, decreased sleep, increased vomiting, and watery stools when fluoxetine hydrochloride was transmitted through breast feeding or breast milk in bottle. These symptoms were reduced when the infant was formula fed. We suggest a possible relationship between colic and associated symptoms and fluoxetine hydrochloride in maternal breast milk.

Adult↗

Effects of indomethacin on brain blood flow and cerebral metabolism in hypoxic newborn piglets.

We tested the hypotheses that in newborn piglets indomethacin (Indo) pretreatment blunts the hyperemic brain blood flow (BF) and alters the cerebral metabolic responses to hypoxia and that these responses are dose dependent. We studied 23 chronically instrumented piglets exposed to graded hypoxia (O2 content: 7.1-0.4 microM O2/ml) after pretreatment with high (5 mg/kg, n = 8)-or low (0.3 mg/kg, n = 6)-dose Indo or placebo (diluent, n = 9). Total and regional brain BF increased significantly with decreasing O2 content values (P < 0.01) in all three groups. However, the rise in the brain BF curves with decreasing O2 content values was significantly (P < 0.05) lower in the high-compared with the low-dose group in all brain regions with the greatest effect in the caudal regions. Furthermore, the BF curves in the placebo-treated animals were similar to the low-dose group. The cerebral metabolic rate of O2 (CMR(O2)) and glucose metabolism were preserved in the three groups over all hypoxic ranges until severe hypoxia (O2 content < or = 1.1 microM O2/ml) was achieved in the high-dose group, when CMR(O2) decreased (P < 0.05), and glucose metabolism increased (P < 0.05). The mean arterial blood pressure in the high-dose group during severe hypoxia was 45 mmHg (P > 0.05). Although coupling of cerebral BF and CMR(O2) was preserved in the three groups, this association was significantly altered with high-dose pretreatment. We conclude that an attenuation in the hypoxia-induced brain perfusion by Indo is dose dependent. Alterations in CMR(O2) and glucose metabolism are observed with high-dose pretreatment during severe hypoxia, and the responses to hypoxia are similar with placebo and low-dose Indo pretreatment.

Animals↗

Endotoxemia and brain bilirubin in the rat.

To investigate the possible role of sepsis with endotoxemia in kernicterus, we studied the effect of endotoxin on accumulation of bilirubin and albumin in rat brain. Male Sprague-Dawley rats were given Escherichia coli endotoxin i.v. After 150 min 10 microCi 125I-bovine serum albumin was given intravenously, followed by a 1-hour bilirubin infusion. Brain bilirubin was significantly higher in the endotoxin group than in the controls (1.34 +/- 0.47 vs. 0.83 +/- 0.31 microgram/g, p < 0.05). However, the difference between the ratios of brain bilirubin to total serum bilirubin at the time of sacrifice were not significant. Total and unbound bilirubin values were significantly higher in the endotoxin-treated group at 165 min. Endotoxemia increased the net accumulation of bilirubin in rat brain, but this increase was probably secondary to an increase in total and unbound bilirubin, rather than an increase in the transfer per se of bilirubin across the blood-brain barrier.

Albumins↗

Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12.

beta-Ketoacyl-acyl carrier protein (ACP) synthase III catalyzes the condensation of acetyl-CoA with malonyl-ACP in dissociated (Type II) fatty acid synthase systems. A synthase III mutant was used to localize the structural gene to the 24.5-min region of the Escherichia coli chromosome, and the defective synthase III allele was designated fabH1. The fabH gene was identified on a 1.3-kilobase NruI-HindIII chromosomal DNA fragment (plasmid pWO114) that complemented the enzymatic defect in fabH1 strains. The NruI-HindIII fragment was sequenced and contained a single open reading frame predicted to encode a 33,517-dalton protein with an isoelectric point of 4.85. The fabH sequence contained an Ala-Cys-Ala tripeptide characteristic of condensing enzyme active sites. A T7 expression system showed that the NruI-HindIII fragment directed the synthesis of a single 34,800-dalton protein. This protein was purified and the order of the amino-terminal 30 residues of the protein corresponded exactly to the amino acid structure predicted from the DNA sequence. The purified protein possessed both acetoacetyl-ACP synthase and acetyl-CoA:ACP transacylase activities, and cells harboring plasmid pWO114 overproduced the two activities, supporting the conclusion that a single protein carries out both reactions. Overproduction of synthase III resulted in a significant increase in shorter-chain fatty acids in the membrane phospholipids. These catalytic properties are consistent with the proposed role of synthase III in the initiation of fatty acid synthesis.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Cloning and nucleotide sequence of the fabD gene encoding malonyl coenzyme A-acyl carrier protein transacylase of Escherichia coli.

We report the cloning and nucleotide sequence of the gene encoding malonyl coenzyme A-acyl carrier protein transacylase of Escherichia coli. Malonyl transacylase has been overexpressed 155-fold compared to a wild-type strain. Overexpression of this enzyme alters the fatty acid composition of a wild-type E. coli strain; increased amounts of cis-vaccenate are incorporated into the membrane phospholipids.

Acyl-Carrier Protein S-Malonyltransferase↗

Hypertrophic cardiomyopathy associated with dexamethasone therapy for bronchopulmonary dysplasia.

The potential induction of cardiac effects by high-dose dexamethasone therapy was evaluated prospectively in 13 respirator-dependent infants with bronchopulmonary dysplasia by means of two-dimensional and M-mode echocardiography. The initial divided dose of dexamethasone was 500 micrograms/kg per day, tapered progressively for as long as 6 weeks. Evaluations were made before treatment and at 3, 7, 14, 21, 28, 35, and 42 days after the start of dexamethasone therapy. This regimen was associated with a significant (p less than 0.01) increase in thickness of the interventricular septum (2.60 +/- 0.09 to 4.00 +/- 0.16 mm), diastolic left ventricular free wall (2.80 +/- 0.13 to 4.06 +/- 0.20 mm), and diastolic right ventricular free wall (1.55 +/- 0.08 to 2.02 +/- 0.12 mm). In addition, seven dexamethasone-treated infants but no control infants had systolic anterior motion of the mitral valve (p less than 0.001). These effects were transient, reached their maximal degree by the third week of treatment, and approached pretreatment conditions by the sixth week of treatment. Ejection fraction was not affected; heart rate and mean arterial pressure were transiently increased during dexamethasone therapy. We conclude that a transient absolute myocardial hypertrophy is associated with dexamethasone therapy in infants with bronchopulmonary dysplasia. The mechanism or mechanisms through which this hypertrophy arises and the cardiopulmonary implications are unclear.

Bronchopulmonary Dysplasia↗

Effects of intraventricular hemorrhage and socioeconomic status on perceptual, cognitive, and neurologic status of low birth weight infants at 5 years of age.

A prospective longitudinal study assessed the effects of intraventricular hemorrhage (IVH) and socioeconomic status on the perceptual, cognitive, and neurologic status of preterm infants at 5 years of age. The preterm group consisted of infants with no IVH, grade I to II IVH, and grade III to IV IVH; a control group of normal term infants was also studied. Outcome was evaluated at 3, 4, and 5 years of age. Twenty-four percent of infants with grade III to IV IVH had abnormal neurologic diagnoses at 5 years of age. Correlations of predictor variables including IVH status, latency of visual evoked response, days of hospitalization, and socioeconomic status with 5-year neurologic outcome indicated that IVH status and visual evoked response at 1, 2, and 3 years continued to have an effect on neurologic outcome, but socioeconomic status and days of hospitalization did not; socioeconomic status did have a significant effect on the McCarthy cognitive scores but not on the perceptual scores at 5 years. Multiple regression analyses revealed that duration of hospitalization (reflecting neonatal morbidity), visual evoked response, and socioeconomic status all have independent effects on the cognitive index, whereas only duration of hospitalization has an independent effect on the perceptual index. These data support the concept that a complex interaction of biologic and environmental risk factors determines the degree of recovery from IVH by high-risk preterm infants.

Cerebral Hemorrhage↗