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D K Stevenson

Publications and source records attributed to D K Stevenson.

At least 109 records · Page 6Linked to original sources
PubMed1996

Evaluation of a fully automated end-tidal carbon monoxide instrument for breath analysis.

We evaluated a novel, portable breath sampler/CO-quantifying instrument [Baby's Breath Carbon Monoxide Analyzer (BB); Natus Medical], developed for use at the bedside or with gas samples collected into bags. Bench tests demonstrated that the CO measurements were linear, accurate, and precise when compared with gas chromatography (GC) results. In vivo tests (n = 30) performed with adults showed excellent correlation between end-tidal breath CO measurements (ETCO) corrected for inhaled CO (ETCOc) as determined by BB and GC. Breath sampling efficiency was 96%. ETCOc measurements and blood carboxyhemoglobin fractions (% of total hemoglobin) corrected for inhaled CO (COHbc) correlated strongly: COHbc = 0.25 ETCOc--0.01 microL/L CO (r2 = 0.97, Sy/x = 0.47, SE slope = 0.01, n = 30). The imprecision, assessed by the mean of the population's CV for triplicate determinations, was 11%. Measurements with healthy and hemolytic term newborns showed that ETCOc values of > 3 microL/L correlated with known hemolytic conditions. We conclude that this instrument is clinically reliable and can be used to noninvasively measure ETCO in neonates and adults.

Adult↗
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↗
PubMed1996

Characterization of porphyrin heme oxygenase inhibitors.

Synthetic metalloporphyrin derivatives of heme have been identified as competitive inhibitors of heme oxygenase, the rate-limiting enzyme in the heme degradation pathway that produces equimolar quantities of carbon monoxide, biliverdin, and bilirubin. Therefore, administration of metalloporphyrin has been proposed as one means to prevent excessive hyperbilirubinemia in human neonates. Tin proto- and meso-porphyrin have been studied for the suppression of neonatal jaundice. However, these compounds are also photosensitizers. This property may limit the clinical use of these compounds, particularly in infants being exposed simultaneously to phototherapy. Via measurements of carbon monoxide, we have studied the photooxidative, metabolic, and inhibitory characteristics of metalloporphyrins that have not yet been studied for this purpose: deuteroporphyrin bisglycol (DBG), iron deuteroporphyrin bisglycol (FeBG), tin deuteroporphyrin bisglycol (SnBG),tin deuteroporphyrin (SnDP), chromium deuteroporphyrin (CrDP), and zinc deuteroporphyrin (ZnDP). Of the six compounds, SnDP, SnBG, and DBG were significantly photoreactive in vitro. Furthermore, in vitro measurements of brain, liver, and spleen heme oxygenase activity inhibition indicated that, of the nonphotoreactive compounds, CrDP and ZnDP were the most potent inhibitors. Only FeBG served as a substrate for the heme oxygenase reaction. The concentration for 50% inhibition with the three tissues ranged from 0.6 to 1.3 microM for CrDP and from 11.0 to 13.5 microM for ZnDP. When 25 mumol CrDP and 50 mumol ZnDP per kilogram body weight were administered to rats given a heme load of 30 mumol/kg body weight, the total body carbon monoxide excretion due to the administered heme load was reduced by 46 and 32%, respectively, at t = 7.5 h, when the experiment was terminated in order to measure heme oxygenase activity. Brain heme oxygenase activity was not affected by the metalloporphyrin treatment. However, both CrDP and ZnDP inhibited liver tissue heme oxygenase activity to 5 and 20%, respectively, whereas only CrDP inhibited spleen tissue heme oxygenase, to 7% of untreated control. Thus, CrDP appears to be the most attractive of the six compounds and deserves further study.

Animals↗
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 cognitive outcome of full-term small for gestational age infants at late adolescence.

OBJECTIVE: To assess the cognitive and academic performance of adolescents who were born small for gestational age (SGA) at term. METHODS: A 17-year historical prospective study was done by matching neonatal data of 1758 infants to the results of the medical and intelligence assessment performed at age 17 years at the army draft board medical examination in Israel. The results of children born SGA (weight at term birth below the third percentile) were compared to those of children who were born appropriate for gestational age (AGA). RESULTS: After adjustment by a multiple linear regression analysis, the mean (+/- standard error of the mean) intelligence test scores were 103.1 +/- 2.9 versus 105.8 +/- 1.5 (P = 0.3) for the males and 100.3 +/- 2.5 versus 104.7 +/- 1.6 (P < .03) for the females. Males born SGA at term were found to have lower educational achievements (having less than 12 years of schooling or attending a vocational school) compared with the AGA group. The odds ratio for this finding after adjustment by a logistic regression analysis was 2.40 (95% confidence interval 1.07-5.39; P < .03). Intranatal events were not found to have an effect on the measured neurodevelopmental outcome. CONCLUSION: Infants born SGA at term have an increased risk for lower cognitive performance and schooling achievements than those born AGA; this result seems to be unrelated to their intranatal course.

Adolescent↗
PubMed1995

Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats exposed to hyperoxia.

Bilirubin is a potent antioxidant in vitro. To determine whether bilirubin also is an antioxidant in vivo, we studied markers of oxidative injury in the Gunn rat model exposed to hyperoxia. Homozygous jaundiced males were mated with heterozygous nonjaundiced females to obtain both jaundiced and nonjaundiced pups within a litter. Once delivered, the pups and their mother were placed in air (21% O2) or hyperoxia (> 95% O2) for 3 d. Both jaundiced and nonjaundiced pups were removed from the chambers daily. Animals were sacrificed and blood was drawn for determination of serum bilirubin, blood thiobarbituric acid-reactive substances (TBARS) by fluorescence assay, serum hydroperoxides, and serum protein oxidation. Tissues (liver, lung, and brain) were assayed for lipid peroxides (TBARS, conjugated dienes [CD], loss of polyunsaturated fatty acid content [PUFA]). We also measured a wide range of serum antioxidants including superoxide dismutase, catalase, glutathione, vitamins A, C, and E, and uric acid. Blood TBARS were significantly decreased in the jaundiced pups compared to the nonjaundiced pups on day 3 of hyperoxia, and blood TBARS were inversely correlated to serum bilirubin on day 3 of hyperoxia (R2 +/- .89). Similar decreases in serum lipid hydroperoxides and serum protein carbonyl content were detected in the jaundiced pups as compared to their nonjaundiced littermates. Other serum antioxidants were not increased in jaundiced animals compared to nonjaundiced animals. Relative lung weight was lower in jaundiced pups exposed to hyperoxia compared to similarly exposed nonjaundiced pups, suggesting a reduction in hyperoxia-induced lung edema. We detected no significant effects of bilirubin on parameters of lipid peroxidation in solid tissues. We conclude that serum bilirubin protects against serum oxidative damage in the first days of life in neonatal Gunn rats exposed to hyperoxia. We speculate that bilirubin is a functionally important transitional antioxidant in the circulation of human neonates and that it may be involved in modulation of injury due to hyperoxia.

Animals↗
PubMed1995

Role of hemolysis in neonatal jaundice associated with glucose-6 phosphate dehydrogenase deficiency.

End-tidal carbon monoxide was measured in 108 newborn infants who had been screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The mean +/- SD end-tidal carbon monoxide did not differ significantly between the G6PD-deficient and the normal neonates, 2.1 +/- 0.6 microliters/L and 2.0 +/- 0.5 microliters/L, respectively, within 12 hours of birth and 1.9 +/- 1.4 microliters/L and 1.5 +/- 0.7 microliters/L, respectively, at 48 to 72 hours after birth. On the basis of these measurements, hemolysis is not a sufficient explanation for jaundice in G6PD-deficient newborn infants in the transitional period.

Bilirubin↗
PubMed1995

Glucose-6-phosphate dehydrogenase deficiency and carboxyhemoglobin concentrations associated with bilirubin-related morbidity and death in Nigerian infants.

Our objective was to determine whether glucose-6-phosphate dehydrogenase (G6PD) deficiency and elevated carboxyhemoglobin (COHb) levels correlated with bilirubin-related morbidity and mortality rates. For this purpose, we studied 55 clinically jaundiced infants admitted to a rural mission hospital in southern Nigeria. Total serum bilirubin levels (range, 80 to 1016 mumol/L (4.7 to 59.4 mg/dl)) correlated with the percentage COHb concentrations (COHb = 0.45 + 0.08 Total serum bilirubin; r = 0.72). Infants were divided into two groups of equal size around the median COHb concentration (COHb range, 0.43% to 5.93% (median = 1.40%), with ambient carbon monoxide of 0.65 +/- 0.03 microL/L). The COHb levels > or = 1.40% were associated with the need for exchange transfusion (15/28, or 54%, vs 5/27, or 19%; p < 0.01) and with an increased incidence of clinical findings compatible with kernicterus (9/28, or 32%, vs 0/27, or 0%; p < 0.01). Mortality rate was 29% (8/29) among infants with higher COHb levels, and 7% (2/28) in those with lower levels (p = 0.08). Thirty-one percent (14/45) of the clinically jaundiced infants tested had G6PD deficiency. Thirty-six percent of the infants with G6PD deficiency died with presumed kernicterus, compared with only 3% (1/31) of the infants with a normal G6PD screening test result (p < 0.01). These data suggest that G6PD deficiency and increased bilirubin production, as indexed by COHb, are associated with jaundice-related morbidity and death in Nigerian infants.

Bilirubin↗
PubMed1995

Photonic detection of bacterial pathogens in living hosts.

The study of pathogenic processes is often limited to ex vivo assays and cell-culture correlates. A greater understanding of infectious diseases would be facilitated by in vivo analyses. Therefore, we have developed a method for detecting bacterial pathogens in a living host and used this method to evaluate disease processes for strains of Salmonella typhimurlum that differ in their virulence for mice. Three strains of Salmonella were marked with bioluminescence through transformation with a plasmid conferring constitutive expression of bacterial luciferase. Detection of photons transmitted through tissues of animals infected with bioluminescent Salmonella allowed localization of the bacteria to specific tissues. In this manner progressive infections were distinguished from those that were persistent or abortive. We observed patterns of bioluminescence that suggested the caecum may play a pivotal role in Salmonella pathogenesis. In vivo efficacy of an antibiotic was monitored using this optical method. This study demonstrates that real time non-invasive analyses of pathogenic events and pharmacological monitoring can be performed in vivo.

Animals↗
PubMed1995

Heme oxygenase activity in the adult rat aorta and liver as measured by carbon monoxide formation.

Rat aorta was homogenized and the 13000 x g supernatant fraction was tested for heme oxygenase (HO) activity by using a sensitive gas chromatographic method to measure carbon monoxide (CO), one of the products of the HO reaction. The rate of NADPH-dependent CO formation, an index of HO activity, was 1.41 +/- 0.40 nmol CO.mg(-1)protein. h(-1) in the rat aorta supernatant fraction and 2.05 +/- 0.55 nmol CO.mg(-1) protein.h(-1) in the rat liver 13000 x g supernatant fraction, a tissue known to contain HO activity. Chromium mesoporphyrin (0.05 mM), an inhibitor of rat liver HO, significantly decreased HO activity by 26% in the aorta supernatant fraction and 50% in the liver supernatant fraction. On the basis of the results of this study, which demonstrated HO-catalyzed CO formation in aortic tissue, and previous observations that CO relaxes vascular smooth muscle, we suggest that a physiological role for CO in vascular smooth muscle relaxation should be further investigated.

Animals↗
PubMed1995

End-tidal carbon monoxide in newborn infants: observations during the 1st week of life.

Serial end-tidal carbon monoxide corrected for ambient CO (ETCOc) levels were measured in an ethnically diverse population of 87 normal newborn infants during the first 5 days of life. The results demonstrate a progressive reduction in ETCOc from 1.6 +/- 0.4 to 0.8 +/- 0.2 ppm. These levels were unrelated to ethnicity, but were inversely related to serum bilirubin levels. We conclude that ETCOc is not a useful indicator for predicting the course of transitional hyperbilirubinemia in the normal newborn infant.

Asian People↗
PubMed1995

Individualized developmental care for very-low-birth-weight premature infants.

Forty very-low-birth-weight neonatal intensive care unit (NICU) infants with birth weights < or = 1,250 g were randomly assigned to treatment or control groups. Behavior of the treatment infants was systematically evaluated, and individualized developmentally oriented care plans were implemented to enhance stability. Treatment babies required fewer days of intermittent mandatory ventilation and continuous positive airway pressure and achieved full enteral feedings sooner. Length of hospital stay and hospital charges were less for treatment than control infants. There were favorable effects on treatment infants' behavioral performance at 42 weeks' postconceptional age. These results support the hypothesis that behaviorally sensitive, developmentally oriented care improves medical and neurodevelopmental outcome in the NICU.

Hospital Charges↗
PubMed1995

Hospital readmission due to neonatal hyperbilirubinemia.

Severe neonatal hyperbilirubinemia can occur without apparent reason in term healthy breast-fed infants and some develop kernicterus. The aim of our study was to assess the incidence of severe hyperbilirubinemia in term healthy newborns discharged from the hospital. From January 1 through December 31, 1994, 6705 infants were delivered at Bikur-Cholim and Misgav-Ladach Community Hospitals. All 1448 newborns discharged with a serum bilirubin level > 10.0 mg/dL were instructed to return to the hospital within 3 days for follow-up, as well as bilirubin determination. Twenty-one newborns with a bilirubin level > 18.0 mg/dL were identified and readmitted at mean +/- standard deviation (SD) 5.5 +/- 1.8 (range, 5 to 10 days of life). This represents 1.7% of the 1220 infants who returned for follow-up examination. Mean +/- SD serum bilirubin levels at readmission were 19.6 +/- 2.5 mg/dL. All but one of the infants were breast-fed. No cases of ABO incompatibility were found and two newborns were glucose-6-phosphate dehydrogenase (G6PD)-deficient. Sepsis work-up and direct Coomb's tests were negative in all cases. None had hemolysis or were found to have any cause for hyperbilirubinemia other than breast-feeding. Phototherapy was provided in all but two cases, and an exchange transfusion was performed in one case. Three additional infants, with bilirubin levels < 10 mg/dL at discharge, were readmitted due to hyperbilirubinemia. One was diagnosed with neonatal hepatitis. We conclude that, based on our study population, 0.36% of term infants may subsequently develop severe neonatal hyperbilirubinemia in the first postnatal week.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗
PubMed1995

Advances in the diagnosis and treatment of neonatal hyperbilirubinemia.

Many controversies remain regarding the role of bilirubin in the developing human. Although kernicterus and cognitive impairment have been linked to hyperbilirubinemia, more recent studies have suggested that there might actually be beneficial effects of bilirubin at a cellular level; thus, the need to better understand the molecular and cellular physiology of this molecule is important. The attempted management of serum or tissue levels of bilirubin may either have implications for long-term neurologic development or interfere with normal body stress responses. Production of CO via heme catabolism also warrants further investigation regarding its role in cell to cell communication or in other important cellular reactions. New methods are being developed to better detect CO under a variety of experimental conditions, as well as to estimate total bilirubin production by measuring the COHb level of pulmonary excretion of CO. The development of new drugs to modulate bilirubin production is the subject of ongoing research. Although some metalloporphyrins already have been used clinically, the advantages and disadvantages of each drug still require further study. These new drugs are not only raising fascinating research questions about heme and bilirubin metabolism, but they may soon revolutionize the way we approach the diagnosis and management of neonatal jaundice, and provide new pharmacologic tools for exploring other aspects of metabolism.

Humans↗