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David K Stevenson

Publications and source records attributed to David K Stevenson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Monitoring age-related susceptibility of young mice to oral Salmonella enterica serovar Typhimurium infection using an in vivo murine model.

Neonates and young children are acutely susceptible to infections by gastrointestinal bacterial pathogens, such as Salmonella enterica serovar Typhimurium (S. typhimurium). To reveal age-related differences in susceptibility to this pathogen, we used in vivo bioluminescence imaging (BLI) to monitor the progression of infection in neonatal (1-wk-old), suckling (2-wk-old), juvenile (4-wk-old), and adult (6-wk-old) BALB/c mice. Mice were orally infected with various doses of a bioluminescent-labeled wild-type or mutant S. typhimurium strain, and progression of infection was monitored by BLI for 2 wks. We found that neonatal and suckling mice were more susceptible to the wild-type strain at inoculum sizes 4 and 2 log(10)'s lower for neonatal and suckling mice, respectively, than those for adult mice. At the lower inocula, newborn mice showed disseminated systemic infection as indicated by the pattern of photon emission assessed by BLI, whereas no bioluminescent signals were detectable in adult mice. In addition, an orgA(-) mutant strain of S. typhimurium with reduced virulence in adult mice produced systemic infection in newborn, suckling, and juvenile mice. Furthermore, as low as 3 log(10) CFU could be detected by BLI in tissue. The present study demonstrates that susceptibility to S. typhimurium infection decreases with age. Also, we established that BLI can be used to monitor the progression of infection in mice. Thus, this model of age-related susceptibility to S. typhimurium using BLI can be used to advance our understanding of the mechanisms involved in newborn susceptibility to infection.

Age Factors↗
PubMed2005

Apigenin decreases hemin-mediated heme oxygenase-1 induction.

Hemin is a strong inducer of heme oxygenase-1 (HO-1) expression in vitro and in vivo. Whereas moderate overexpression of HO-1 is protective against oxidative stress, uncontrolled levels of HO-1 can be detrimental. Therefore, we evaluated the effects of apigenin (APG), a flavonoid involved in a number of phosphorylation pathways and also known to inhibit inducible genes, such as iNOS and COX-2, on HO-1 expression. Incubation of mouse embryonic fibroblasts with APG (5--40 microM) decreased hemin-induced HO-1 protein and mRNA expression. APG also reduced the induction of HO-1 promoter activity, as assessed by bioluminescence imaging, in NIH3T3 cells transfected with the 15-kb HO-1 promoter fused with the reporter gene luciferase (HO-1-luc). Furthermore, through the use of specific inhibitors, APG's effect was found to be unrelated to its PKC, CK 2, PI 3 K, p38, or ERK inhibitory activities. Quercetin (10--40 microM), also a flavonoid, also inhibited hemin-induced HO-1 expression. Additionally, in vivo studies using HO-1-luc transgenic mice showed that APG (50 mg/kg) decreased hemin-induced HO activity and HO-1 protein expression in the liver. These results suggest that hemin-induced HO-1 expression can be attenuated by flavonoids, such as APG.

Actins↗
PubMed2005

Glucose-6-phosphate dehydrogenase activity in term and near-term, male African American neonates.

BACKGROUND: We determined values for glucose-6-phosphate dehydrogenase (G-6-PD) activity in African American neonates. METHODS: G-6-PD activity was measured on umbilical cord blood from term and near-term healthy, male neonates. Neonates were stratified according to the number of neonates for each numerical unit of G-6-PD activity. Corrected end tidal carbon monoxide (ETCOc), a non-invasive index of hemolysis, was performed on each neonate. At least one predischarge transcutaneous bilirubin determination was performed. RESULTS: Five hundred neonates were studied. Two subpopulations were apparent, with no overlap between the subgroups. Mean value for the 64 (12.8%) infants with the lower values (G-6-PD deficient) was 2.7+/-1.1 U/g Hb, range 0.4-6.6 U/g Hb, while that for the 436 neonates with the higher values (G-6-PD normal) was 21.8+/-2.9 U/g Hb, range 14.5-33.8 U/g Hb. No significant differences in activity were noted between those neonates <37 weeks gestational age and those >37 weeks. Enzyme activity in the lower range in both groups was not related to the development of hyperbilirubinemia. G-6-PD enzyme activity did not correlate with ETCOc values either for the entire cohort or for the individual subsets. CONCLUSIONS: G-6-PD-deficient neonates formed a separate subgroup from those with normal enzyme activity. The data supplied should facilitate interpretation of G-6-PD test results.

Black or African American↗
PubMed2005

Reduction in red blood cell transfusions among preterm infants: results of a randomized trial with an in-line blood gas and chemistry monitor.

BACKGROUND: Critically ill, extremely premature infants develop anemia because of intensive laboratory blood testing and undergo multiple red blood cell (RBC) transfusions in the early weeks of life. To date, researchers have had only limited success in finding ways to reduce transfusions significantly in this patient population. OBJECTIVE: To reduce RBC transfusions for these infants by using a point-of-care bedside monitor that returns analyzed blood to the patient. DESIGN, SETTING, AND PATIENTS: This was a prospective, 2-center, randomized, open, controlled, clinical trial with a 1:1 assignment of extremely low birth weight infants (weighing 500-1000 g at birth) to control or monitor groups and analysis with the intention-to-treat approach. Predefined RBC transfusion criteria were applied uniformly in the 2 groups. INTERVENTIONS: Clinical treatment of study subjects with an in-line, ex vivo, bedside monitor that withdraws blood through an umbilical artery catheter, analyzes blood gases and sodium, potassium, and hematocrit levels, and returns the sample to the patient. MAIN OUTCOME MEASURES: The total volume and number of RBC transfusions during the first 2 weeks of life and the total volume of blood removed for laboratory testing. RESULTS: The trial was terminated prematurely when one center's NICU changed its standard method of laboratory testing. In the first 2 weeks of life, there was a nonsignificant 17% lower cumulative RBC transfusion volume in the monitor group (n = 46), compared with the control group (n = 47). However, data from the first week only (the period of greater catheter use) demonstrated a significant 33% lower cumulative RBC transfusion volume in the monitor group. Cumulative phlebotomy loss was approximately 25% less in the monitor group throughout the 2-week study period. There was no difference between groups in neonatal mortality, morbidity, and neurodevelopmental outcome rates at 18 to 24 months. This is the first randomized trial documenting that RBC transfusions administered to neonates can by reduced by decreasing laboratory phlebotomy loss. CONCLUSIONS: As long as an umbilical artery catheter is available for blood sampling with an in-line blood gas and chemistry monitor, significant reductions in neonatal RBC transfusions can be achieved. The patients most likely to benefit from monitor use are the smallest, most critically ill newborns.

Anemia, Neonatal↗
PubMed2004

Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome?

Infant respiratory distress syndrome (RDS) involves inflammatory processes, causing an increased expression of inducible heme oxygenase with subsequent production of carbon monoxide (CO). We hypothesized that increased production of CO during RDS might be responsible for increased plasma levels of vasodilatory cGMP and, consequently, low blood pressure observed in infants with RDS. Fifty-two infants (no-RDS, n = 21; RDS, n = 31), consecutively admitted to the neonatal intensive care unit (NICU) between January and October 2003 were included. Hemoglobin-bound carbon monoxide (COHb), plasma cGMP, plasma nitric oxide (NOx), and bilirubin were determined at 0-12, 48-72, and at 168 h postnatally, with simultaneous registration of arterial blood pressure. Infants with RDS had higher levels of cGMP and COHb compared with no-RDS infants (RDS vs. no-RDS: cGMP ranging from 76 to 101 vs. 58 to 82 nmol/l; COHb ranging from 1.2 to 1.4 vs. 0.9 to 1.0%). Highest values were reached at 48-72 h [RDS vs. no-RDS mean (SD): cGMP 100 (39) vs. 82 (25) nmol/l (P < 0.001); COHb 1.38 (0.46) vs. 0.91 (0.26)% (P < 0.0001)]. Arterial blood pressure was lower and more blood pressure support was needed in RDS infants at that point of time [RDS vs. no-RDS mean (SD): mean arterial blood pressure 33 (6) vs. 42 (5) mmHg (P < 0.05)]. NOx was not different between groups and did not vary with time. Multiple linear regression analysis showed a significant correlation between cGMP and COHb, suggesting a causal relationship. Mean arterial blood pressure appeared to be primarily correlated to cGMP levels (P < 0.001). We conclude that a CO-mediated increase in cGMP causes systemic vasodilation with a consequent lower blood pressure and increased need for blood pressure support in preterm infants with RDS.

Biomarkers↗
PubMed2004

Phototherapy and photo-oxidation in premature neonates.

OBJECTIVE: The potential for photo-oxidation during phototherapy in premature neonates was assessed by measuring parameters reflective of photo-oxidation. METHODS: Blood was sampled from premature neonates prior to, and after 4 and 24 h of phototherapy, respectively. Total plasma bilirubin (TPB), blood carboxyhemoglobin corrected for inspired carbon monoxide (COHbc) (a sensitive index of heme catabolism), blood thiobarbituric acid reacting substances (TBARS) (a measure of lipid peroxidation), and plasma protein carbonyls (representative of protein oxidation) were determined. Study measurements were compared with baseline values both for the entire study group, and also individually for subgroups < and > or = 1.5 kg birthweight, respectively. The percentage difference (%delta) between baseline and the 24-hour measurement was calculated for each parameter. RESULTS: Forty-one premature neonates (mean [+/- SD] gestational age 30.5 +/- 2.7 weeks and birthweight 1,499 +/- 448 g) were studied. Mean TPB values decreased from a baseline of 9.1 +/- 2.3 to one of 7.2 +/- 2.8 mg/dl, p < 0.01, during the first 24 h of phototherapy. For the entire patient sample, neither COHbc, TBARS or protein carbonyl values increased significantly over baseline measurements: COHbc: 0.90 +/- 0.26% vs. 0.92 +/- 0.32%; TBARS: 19.0 +/- 5.6 vs. 18.0 +/- 4.5 nmol/ml, and protein carbonyls 7.73 +/- 3.78 vs. 7.63 +/- 3.56 U/ml (baseline and 24-hour samples only are shown in the abstract). Similarly, for the entire group, %delta (mean, interquartile range) were not significantly different between COHbc [-3.77 (-15.89-17.65)%], TBARS [-7.47 (-17.37-7.38)%], and protein carbonyls [-1.47 (-28.51-43.48)%], respectively. For subgroup analysis of neonates < or > or = 1.5 kg birthweight, respectively, no significant increases in COHbc, TBARS or protein carbonyls were documented. A significant increase in %delta for COHbc in the <1.5 kg birthweight subgroup compared with those > or =1.5 kg, possibly indicative of hemolysis, was not matched by similar changes in %delta for TBARS or protein carbonyls, and may therefore not be a result of photo-oxidation. CONCLUSIONS: Except for changes in %delta in COHbc alone and in the smallest babies only, overall, short term phototherapy in premature infants was effective in reducing TPB concentrations without associated evidence reflective of photo-oxidation.

Bilirubin↗
PubMed2004

End tidal carbon monoxide levels are lower in women with gestational hypertension and pre-eclampsia.

BACKGROUND: The possible role of heme oxygenase and its byproduct carbon monoxide (CO) in the regulation of blood pressure is under investigation. The aim of this study was to compare end tidal breath CO (ETCO) levels in women with gestational hypertension (GH) or pre-eclampsia to the levels in healthy pregnant and nonpregnant women. MATERIALS AND METHODS: We prospectively performed ETCO measurements corrected for ambient CO (ETCOc) in two medical centers (Stanford, CA and Cleveland, OH). A Natus CO-Stat End Tidal Breath Analyzer (Natus Medical Inc., San Carlos, CA) was used. The study group included a convenience sample of 31 women with GH/pre-eclampsia (PE). Control groups included 46 nonpregnant healthy women, 44 first-trimester and 48 third-trimester pregnant healthy women. RESULTS: Mean+/-SD ETCOc measurements were significantly lower in the GH/PE group compared to first-trimester (p=0.004) and third-trimester (p=0.001) normotensive pregnant and nonpregnant women (p=0.002) (1.36+/-0.30 vs 1.76+/-0.47, 1.72+/-0.42 and 1.78+/-0.54 ppm, respectively). The ETCOc values were < or =1.6 ppm in 89% of GH/PE women compared with, respectively, only 45, 54, and 46% of nonpregnant, first- and third-trimester normotensive pregnant women (p<0.05). ETCO measurements were not influenced by maternal age, parity, ethnicity, body mass index, gestational age or presence of household smokers. In the two centers, the controls had a similar mean ETCOc and the differences found remained significant when results for each center were analyzed separately. CONCLUSIONS: ETCOc levels were found to be significantly lower in women with GH/PE. Further investigation is required to determine if the lower CO levels reflect a deficient compensatory response to the increase in blood pressure or whether these are primary changes of significance to our understanding of the pathogenesis of GH/PE.

Adult↗
PubMed2004

End-tidal breath carbon monoxide measurements are lower in pregnant women with uterine contractions.

OBJECTIVE: To compare the levels of end-tidal carbon monoxide (ETCOc) among women with and without uterine contractions in term and preterm pregnancies. STUDY DESIGN: In all, 55 nonsmoking healthy pregnant women were enrolled. ETCOc levels were compared among women with contractions (10 preterm and 13 term) and 32 women without contractions (34-41 weeks gestation). RESULTS: Maternal age, gravidity and parity were similar among study and control groups. ETCOc levels were significantly lower among women that had uterine contractions (0.99+/-0.38 parts per million (ppm) and 1.15+/-0.34 p.p.m. respectively), compared to women with no contractions (1.70+/-0.52 p.p.m., P<0.002). However, there was no significant difference in the ETCOc levels between women with preterm or term contractions (P=0.48). CONCLUSIONS: Low levels of ETCOc are associated with preterm and term uterine contractions.

Adult↗
PubMed2004

NICHD Conference on Kernicterus: Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench-to-Bedside--Diagnostic Methods and Prevention and Treatment Strategies.

In July 2003, the National Institute of Child Health and Human Development (NICHD) organized a consensus conference, where a group of experts were invited to review and discuss the current state of knowledge regarding neonatal hyperbilirubinemia and identify areas in which where future research should be directed. This paper summarizes the presentations addressing the current methodologies for direct and noninvasive assessments of serum total bilirubin concentrations as well as prevention and treatment strategies for the management of neonatal hyperbilirubinemia.

Bilirubin↗
PubMed2004

Phototherapy: current methods and future directions.

Phototherapy is the most common therapeutic intervention used for the treatment of hyperbilirubinemia. Although it has become a mainstay since its introduction in 1958, a better understanding of the photobiology of bilirubin, characteristics of the phototherapy devices, the efficacy and safety considerations of phototherapy applications, and improvements in spectroradiometers and phototherapy devices are necessary for more predictable and improved clinical practices and outcomes. A step forward in instituting consistent, uniform, and effective use of phototherapy is the recent American Academy of Pediatrics clinical guideline on the management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation, which outlines a clinical strategy for the diagnosis of hyperbilirubinemia and contains direct recommendations for the application of phototherapy. This article reviews the parameters that determine the efficacy of phototherapy, briefly discusses current devices and methods used to deliver phototherapy, and speculates on future directions and studies that are still needed to complement our presently incomplete knowledge of the facets of this common mode of therapy.

Bilirubin↗
PubMed2004

Continuous, noninvasive, and localized microvascular tissue oximetry using visible light spectroscopy.

BACKGROUND: The authors evaluated the ability of visible light spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (StO2) in small, thin tissue volumes. METHODS: In pigs, StO2 was measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%), and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation). RESULTS: In pigs, normoxic StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2 (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia). CONCLUSIONS: VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.

Animals↗
PubMed2004

Cesarean delivery rates and neonatal morbidity in a low-risk population.

OBJECTIVE: To estimate the relationship between case-mix adjusted cesarean delivery rates and neonatal morbidity and mortality in infants born to low-risk mothers. METHODS: This retrospective cohort study used vital and administrative data for 748,604 California singletons born without congenital abnormalities in 1998-2000. A total of 282 institutions was classified as average-, low-, or high-cesarean delivery hospitals based on their cesarean delivery rate for mothers without a previous cesarean delivery, in labor at term, with no evidence of maternal, fetal, or placental complications. Neonatal mortality, diagnoses, and therapeutic interventions determined by International Classification of Diseases, 9th Revision, Clinical Modification codes, and neonatal length of stay were compared across these hospital groupings. RESULTS: Compared with average-cesarean delivery-rate hospitals, infants born to low-risk mothers at low-cesarean delivery hospitals had increased fetal hemorrhage, birth asphyxia, meconium aspiration syndrome, feeding problems, and electrolyte abnormalities (P <.02). Infused medication, pressors, transfusion for shock, mechanical ventilation, and length of stay were also increased (P <.001). This suggests that some infants born in low-cesarean delivery hospitals might have benefited from cesarean delivery. Infants delivered at high-cesarean delivery hospitals demonstrated increased fetal hemorrhage, asphyxia, birth trauma, electrolyte abnormalities, and use of mechanical ventilation (P <.001), suggesting that high cesarean delivery rates themselves are not protective. CONCLUSION: Neonatal morbidity is increased in infants born to low-risk women who deliver at both low- and high-cesarean delivery-rate hospitals. The quality of perinatal care should be assessed in these outlier hospitals. LEVEL OF EVIDENCE: III

Adult↗
PubMed2004

Characterization of coelenterazine analogs for measurements of Renilla luciferase activity in live cells and living animals.

In vivo imaging of bioluminescent reporters relies on expression of light-emitting enzymes, luciferases, and delivery of chemical substrates to expressing cells. Coelenterazine (CLZN) is the substrate for a group of bioluminescent enzymes obtained from marine organisms. At present, there are more than 10 commercially available CLZN analogs. To determine which analog is most suitable for activity measurements in live cells and living animals, we characterized 10 CLZN analogs using Renilla luciferase (Rluc) as the reporter enzyme. For each analog, we monitored enzyme activity, auto-oxidation, and efficiency of cellular uptake. All CLZN analogs tested showed higher auto-oxidation signals in serum than was observed in phosphate buffer or medium, mainly as a result of auto-oxidation by binding to albumin. CLZN-f, -h, and -e analogs showed 4- to 8-fold greater Rluc activity, relative to CLZN-native, in cells expressing the enzyme from a stable integrant. In studies using living mice expressing Rluc in hepatocytes, administration of CLZN-e and -native produced the highest signal. Furthermore, distinct temporal differences in signal for each analog were revealed following intravenous or intraperitoneal delivery. We conclude that the CLZN analogs that are presently available vary with respect to hRluc utilization in culture and in vivo, and that the effective use of CLZN-utilizing enzymes in living animals depends on the selection of an appropriate substrate.

Animals↗
PubMed2004

To tap or not to tap: high likelihood of meningitis without sepsis among very low birth weight infants.

CONTEXT: Neonatal meningitis is associated with significant morbidity and mortality. We speculated that meningitis may be underdiagnosed among very low birth weight (VLBW) infants because of the failure to perform lumbar punctures (LPs) in infants with suspected sepsis. OBJECTIVE: This study was undertaken to review the epidemiology of late-onset meningitis in VLBW (401-1500 g) infants and to evaluate the concordance of cerebrospinal fluid (CSF) and blood culture (BC) results. METHODS: VLBW infants (excluding those with intraventricular shunts) born at centers of the National Institute of Child Health and Human Development Neonatal Research Network from September 1, 1998, through December 31, 2001, were studied. Late-onset meningitis was defined by culture-based criteria and classified as meningitis with or without associated sepsis. Unadjusted comparisons were made using chi2 tests and adjusted comparisons using regression models. RESULTS: Of 9641 VLBW infants who survived >3 days, 2877 (30%) had > or = 1 LPs, and 6056 (63%) had > or = 1 BC performed after day 3. One hundred thirty-four infants had late-onset meningitis (1.4% of all patients; 5% of those with an LP). Pathogens associated with meningitis were similar to those associated with sepsis. One third (45 of 134) of the infants with meningitis had negative BCs. Lower gestational age and prior sepsis increased risk for meningitis. Compared with uninfected infants, those with meningitis had a longer time on mechanical ventilation (28 vs 18 days), had longer hospitalizations (91 vs 79 days), were more likely to have seizures (25% vs 2%), and were more likely to die (23% vs 2%). CONCLUSIONS: Meningitis is a serious complication among VLBW infants, associated with increased severity of illness and risk of death. Of note, one third of the infants with meningitis had meningitis in the absence of sepsis. Because CSF cultures were performed only half as often as BCs, this discordance in blood and CSF culture results suggests that meningitis may be underdiagnosed among VLBW infants.

Humans↗