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L L Wright

Publications and source records attributed to L L Wright.

At least 55 records · Page 3Linked to original sources
PubMed1996

Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: To identify prenatal and perinatal risk and protective factors for grade III and IV intracranial hemorrhage (ICH) in 4795 singleton infants (weight, < or = 1500 g). METHOD: Prenatal and perinatal risk and protective factors for ICH were examined initially by univariate analysis and adjusted for year of birth, followed by multivariate logistic regression analysis that adjusted simultaneously for the effects of year of birth and prenatal and perinatal characteristics. SETTING: Seven tertiary care neonatal-perinatal centers. RESULTS: By univariate analysis, African-American race, prenatal care, older maternal age, hypertension or preeclampsia, antenatal steroid administration, cesarean section delivery, increasing birth weight, increasing gestational age, and female gender of the infant were protective prenatal or perinatal factors. Antepartum hemorrhage, the presence of labor, and breech presentation were perinatal factors that were associated with an increased risk of ICH. By using staged logistic regression, a model of combined prenatal and perinatal characteristics that influenced grade III and IV ICH was developed. Significant protective factors against ICH included a complete course of antenatal steroid therapy, African-American maternal race, female gender of the infant, hypertension or preeclampsia with no antepartum hemorrhage, increasing gestational age, and increasing birth weight. CONCLUSION: Antenatal steroid administration is a therapeutic intervention that is associated with a decreased risk for neonatal grade III and IV ICH.

Analysis of Variance↗
PubMed1996

Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991 to 1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry of all VLBW neonates cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Of 6911 infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood culture-proven sepsis. The vast majority of infection (73%) were caused by gram-positive organisms, with coagulase-negative staphylococci accounting for 55% of all infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of infection included intubation, respiratory distress syndrome, prolonged ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with bronchopulmonary dysplasia, those with late-onset sepsis had a significantly longer duration of mechanical ventilation (45 vs 33 days; p <0.01). Late-onset sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW neonates with and without late-onset sepsis was 86 and 61 days, respectively (p <0.001). Even after adjustment for other complications of prematurity, including intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia, infants with late-onset sepsis had a significantly longer hospitalization (p <0.001). Moreover, neonates in whom late-onset sepsis developed were significantly more likely to die than those who were uninfected (17% vs 7%; p <0.000 1), especially if they were infected with gram-negative organisms (40%) or fungi (28%). Deaths attributed to infection increased with increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life were attributed to infection, 45% of deaths after 2 weeks were related to infection. CONCLUSIONS: Late-onset sepsis is a frequent and important problem among VLBW preterm infants. Successful strategies to decrease late-onset sepsis should decrease VLBW mortality rates, shorten hospital stay, and reduce costs.

Age of Onset↗
PubMed1996

Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Early-onset sepsis (occurring within 72 hours of birth) is included in the differential diagnosis of most very low birth weight (VLBW) neonates. To determine the current incidence of early-onset sepsis, risk factors for disease, and the impact of early-onset sepsis on subsequent hospital course, we studied a cohort of 7861 VLBW neonates (401 to 1500 gm) admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991-1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry on all VLBW neonates born or cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Blood culture-proven early-onset sepsis was uncommon, occurring in only 1.9% of VLBW neonates. Group B streptococcus was the most frequent pathogen associated with early-onset sepsis (31%), followed by Escherichia coli (16%) and Haemophilus influenzae (12%). Decreasing gestational age was associated with increased rates of infection. Antibiotic therapy for suspected sepsis is frequently initiated at birth in VLBW neonates. Almost half of the infants in this cohort were considered to have clinical sepsis and continued to receive antibiotics for 5 or more days, despite a negative blood culture result in 98% of cases. These findings underscore the difficulty of ruling out sepsis in the symptomatic immature neonate and the special concern for culture-negative clinical sepsis in the face of maternal antibiotic use. Neonates with early-onset sepsis were significantly more likely to have subsequent comorbidities, including severe intraventricular hemorrhage, patent ductus arteriosus, and prolonged assisted ventilation. Although 26% of VLBW neonates with early-onset sepsis died, only 4% of the 950 deaths that occurred in the first 72 hours of life were attributed to infection. For those infants discharged alive, early-onset sepsis was associated with a significantly prolonged hospital stay (86 vs 69 days; p <0.02). CONCLUSIONS: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants. Improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected VLBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected.

Age of Onset↗
PubMed1996

Interlaboratory variability of bilirubin measurements.

During an 8-month study, 14 laboratories used automated analytical systems to measure total bilirubin concentrations in lyophilized bovine specimens containing 38, 169, and 253 micromol/L bilirubin (2.2, 9.9, and 14.8 mg/dL, respectively). The measured mean +/- SD (n, range) were: 39 +/- 7 micromol/L (n = 90, 31-53) [2.3 +/- 0.4 mg/dL (1.8-3.1)]; 176 +/- 29 micromol/L (n = 89, 146-222) [10.3 +/- 1.7 mg/dL (8.5-13.0)]; and 260 +/- 43 micromol/L (n = 103, 208-316) [15.2 +/- 2.5 mg/dL (12.1-18.5)]. In comparison with target values, measurements were consistently lower at 4, higher at 6, and within +/- 4% at 4 laboratories for each of the three concentrations. The measured values for each concentration remained fairly constant during the study at each laboratory. We conclude that bilirubin measurements differed significantly from the established target values at most of the participating laboratories.

Animals↗
PubMed1995

Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Network, November 1989 to October 1990.

OBJECTIVE: Our purpose was to describe the neonatal outcomes of 1804 very-low-birth-weight (< or = 1500 gm) infants delivered between November 1989 and October 1990 in the participating centers of the National Institute of Child Health and Human Development Neonatal Research Network. STUDY DESIGN: In an observational study sociodemographic, pregnancy, and delivery data were collected soon after birth, and neonatal and outcome data at discharge, at 120 days, or at death. RESULTS: Maternal and birth weight characteristics included 64% black, 29% white; 71% single mothers; 18% no prenatal care; 17% antenatal steroids; and 12% multiple gestations. Birth weight distributions included 18% weighing 501 to 750 gm, 23% 751 to 1000 gm, 28% 1001 to 1250 gm, and 31% 1251 to 1500 gm. Survival was 39% at < 751 gm birth weight, 77% at 751 to 1000 gm, 90% at 1001 to 1250 gm, and 93% at 1251 to 1500 gm. Survival was 15% to 18% at < or = 23 weeks' gestation, 54% at 24 weeks, 59% at 25 weeks, and 71% at 26 weeks. Surfactant was administered to 45% of the 56% of infants with respiratory distress syndrome. Morbidity, including intraventricular hemorrhage (40%), septicemia (24%), symptomatic patent ductus arteriosus (22%), and necrotizing entercolitis (8%), increased with decreasing birth weight. Oxygen was administered for > or = 28 days to 82% of < 751 gm infants, 49% of 751 to 1000 gm infants, and 10% of > 1001 gm infants. Steroids were administered to 28% of infants who required oxygen for > or = 28 days. Mean hospital stay was 62 days for survivors and 18 days for infants who died. There were large intercenter variations in mortality and morbidity. CONCLUSION: Mortality and morbidity in very-low-birth-weight infants improved in 1989 to 1990 without an increase in morbidity or length of hospital stay. The threshold of the improved survival was > or = 24 weeks and 601 to 700 gm. Although such data are reassuring, the rate of major morbidity in < 1001 gm birth weight infants continues to be high.

Birth Weight↗
PubMed1995

Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, May 1991 through December 1992.

OBJECTIVES: Our goals were to determine the mortality risk for infants weighing 501 to 1500 gm according to gestational age, birth weight, and gender and to document birth weight-related changes in mortality and morbidity over a 5-year time period. STUDY DESIGN: In this observational study perinatal data were prospectively collected by the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network from May 1991 through December 1992 and compared with the corresponding data from 1987 through 1990. Standard definitions were used to record sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death. RESULTS: The 1991 and 1992 cohort included 4279 in-born infants. Among their mothers 10% were < 18 years old; 55% were black, 31% were white, and 11% were Hispanic; 14% had received no prenatal care; and 20% had received antenatal corticosteroids. Multiple gestations accounted for 20% of the births. Fifty percent of the infants were delivered by cesarean section. During 1991 and 1992 the overall survival for infants weighing 501 to 1500 gm at birth was 81%, compared with 74% in 1987 and 1988. Survival at birth weight 501 to 750 gm was 44%; it was 81% at 751 to 1000 gm, 92% at 1001 to 1250 gm, and 95% between 1251 and 1500 gm. Female infants had a significantly greater chance of surviving than male infants at similar birth weights and gestational ages. At any given gestational age, smaller infants were less likely to survive. Survival in all birth weight categories increased between 1987 and 1992, without accompanying increases in medical morbidity. Major morbidity increased with decreasing birth weight and included late-onset septicemia 22%, chronic lung disease (oxygen dependence at 36 weeks' corrected age) 18%, severe intraventricular hemorrhage (grades III and IV) 11%, and necrotizing enterocolitis 5%. Twelve percent of all infants were treated with corticosteroids for chronic lung disease, including 36% of infants who were oxygen dependent at age 28 days. The mean length of hospital stay was 69 days for survivors and 18 days for infants who died. CONCLUSIONS: Mortality for infants between 501 and 1500 gm at birth has declined over the past 5 years. There are interactions between birth weight, gestational age, gender, and survival rate. This increase in survival was not accompanied by an increase in medical morbidity.

Apgar Score↗
PubMed1995

The immunocytochemical detection of amino-acid neurotransmitters in paraformaldehyde-fixed tissues.

In this study, we show that specific antibodies can be raised against paraformaldehyde conjugates of amino acids, including the neurotransmitters glycine, gamma-amino-butyric acid and glutamate, and a non-neuroactive amino acid, glutamine. These antibodies against paraformaldehyde conjugates specifically detect the above amino acids in paraformaldehyde-fixed tissues. The penetration of antibodies into paraformaldehyde-fixed tissues is much superior to the penetration of antibodies into glutaraldehyde-fixed tissues; hence good labeling can be observed through the depth of the tissues. Unlike glutaraldehyde, fixation with paraformaldehyde does not give rise to high levels of tissue autofluorescence and, thus, these antibodies are very effective for immunofluorescence studies. Furthermore we suggest that the ability of these antibodies to detect amino acids in paraformaldehyde-fixed tissues will permit their use in situations where it is necessary to detect other other fixation-sensitive antigens, such as neurotransmitter receptors and transporters.

Amino Acids↗
PubMed1994

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. METHODS: In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. RESULTS: Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. CONCLUSIONS: Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

Adult↗
PubMed1994

Semiportable electrochemical instrument for determining carbon monoxide in breath.

Measurements of carbon monoxide (CO) in breath can be used for the diagnosis of hemolytic disease. A small, semiportable, easy-to-operate CO instrument was developed at Stanford University and tested at 12 Neonatal Research Network Centers of the National Institute of Child Health and Human Development. A syringe pump delivers 7.7 mL of sample per minute through an activate carbon filter to an electrochemical (EC) sensor having a sensitivity of 0.10 +/- 0.01 V per 1 microL/L CO in air. The electronically processed sensor signal is displayed on a digital multimeter. For a typical end-tidal CO measurement, corrected for inhaled CO, three 10- to 12-mL breath and room air samples are manually or mechanically collected and analyzed. CO determination in breath samples from 108 healthy, 1-day-old infants of nonsmoking mothers compared favorably with determinations by gas chromatography (GC), 1.3 +/- 0.8 vs 1.2 +/- 0.8 (mean +/- SD), respectively, with a regression equation of EC = 0.95 GC+0.13 (r2 = 0.98). The results demonstrate that the EC-CO instrument yields results that are comparable with those obtained by the more difficult to perform GC assay.

Breath Tests↗
PubMed1994

Bilirubin production in healthy term infants as measured by carbon monoxide in breath.

To describe total bilirubin production in healthy term infants, we measured the end-tidal breath CO, corrected for ambient CO (ETCOc), with an automated sampler and electrochemical (EC) CO instrument. For infants of mothers with a negative Coombs' test, the ETCOc was 1.3 +/- 0.7 microL/L (n = 397) and the serum bilirubin on day 3 postpartum was 73 +/- 35 mg/L (n = 381). In contrast, the ETCOc for infants with ABO or Rh incompatibility, a positive direct Coombs' test, and bilirubin > 130 mg/L (n = 9) was significantly higher, 1.8 +/- 0.8 microL/L, than for those who had a positive Coombs' test result but whose bilirubin was < or = 130 mg/L (n = 12), 1.0 +/- 0.5 microL/L (P < 0.05). At 2 to 8 h postpartum seven term babies from mothers with insulin-dependent diabetes had ETCOc of 1.8 +/- 0.7 microL/L, significantly higher than that in the other term infants [1.3 +/- 0.7 microL/L (n = 390), P < 0.04]. Their bilirubin concentration at 72 +/- 12 h was also higher: 121 +/- 45 mg/L (n = 7) vs 73 +/- 34 mg/L (n = 374; P = 0.03). We conclude that ETCOc measurements may be helpful in understanding the mechanisms of jaundice in healthy term infants in a variety of conditions.

Asian↗
PubMed1993

Quantitative study of primary sensory neurone populations of three species of elasmobranch fish.

In order to assess the ability of sharks and rays to sense pain, the proportion of myelinated versus unmyelinated sensory fibres in the dorsal roots and the diameter spectrum of cells in the dorsal root ganglia of three species of elasmobranch fish were ascertained. Electron micrographs were used to count the numbers of myelinated and unmyelinated fibres in montages of whole dorsal roots of the long-tailed stingray (Himantura sp.), the shovelnose ray (Rhinobatus battilum), and small specimens of the black-tip shark (Carcharhinus melanopterus). The diameters of dorsal root ganglion cells in each species were measured by using the light microscope. Less than 1% of the dorsal root axons in the long-tailed stringray and a large specimen of the shovelnose were unmyelinated, whereas in smaller shovelnose rays and in the small black-tipped sharks, from 14% to 38% of axons were unmyelinated. Unmyelinated fibres differed from those in mammalian nerves in that there was a one-to-one association of the fibre with a Schwann cell. We conclude from these observations that myelination was incomplete in the black-tipped sharks and the smaller specimens of the shovelnose rays. The distribution of the diameter of cells of the dorsal root ganglia of these species was unimodal, resembling the diameter range that has been reported for the somata of myelinated fibres in the cat. We interpret these results as indications that sharks and rays lack the neural apparatus essential for the sensation of pain and we suggest that, to these life forms, the perception of pain might have little relevance to survival.

Animals↗
PubMed1993

Conformational changes induced in herpes simplex virus DNA polymerase upon DNA binding.

Herpesvirus DNA polymerases are prototypes for alpha-like DNA polymerases and important targets for antiherpesvirus drugs. We have investigated changes in the catalytic subunit of herpes simplex virus DNA polymerase following DNA binding by using the techniques of endogeneous fluorescence quenching and limited proteolysis. The fluorescence studies revealed a reduction in the rate of quenching by acrylamide in the presence of DNA without changes in the wavelength of the emission peak or in the lifetime of the fluorophore, consistent with the possibility of conformational changes. Strikingly, the proteolysis studies revealed that binding to a variety of natural and synthetic DNA and RNA molecules induced the appearance of a new cleavage site for trypsin near residue 1060 of the protein and increased cleavage by trypsin near the center of the protein. The extent of these cleavages correlated with the affinity of the polymerase for these ligands. These data provide strong evidence that binding to nucleic acid polymers induces substantial localized conformational changes in the polymerase. The locations of enhanced tryptic cleavage near sites implicated in substrate recognition and interaction with a processivity factor suggest that the conformational changes are important for catalysis and processivity of this prototype alpha-like DNA polymerase. Inhibition of these changes may provide a mechanism for antiherpesvirus drugs.

Catalysis↗
PubMed1993

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↗