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Biomedical subjects

D K Stevenson

Publications and source records attributed to D K Stevenson.

At least 91 records · Page 5Linked to original sources

Neonatal severity of illness scoring systems: a comparison.

Several different scoring systems have been developed to predict neonatal morbidity and mortality. In this investigation we compared the utility of four severity of illness scoring systems (SISS) as predictors of days on ventilatory (DOV), length of hospital stay (LOS), and mortality in very-low-birth weight (VLBW) premature infants who required mechanical ventilation. The SISS assessed were the Score for Neonatal Acute Physiology (SNAP); the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP + PE); Clinical Risk Index for Babies (CRIB), and the Sinkin Score at 12 hours (SS12). Results revealed significant correlations among the SS12, SNAP, SNAP + PE, CRIB, birth weight (BW), DOV, and LOS. However, none of the systems we assessed offered striking advantage over BW in a VLBW ventilated group.

Evaluation Studies as Topic↗

Neonatal hypoglycemia, Part I: Background and definition.

Hypoglycemia in the neonate remains a common problem. The association of low blood glucose concentrations and abnormal development has prompted extensive research into the anticipation, evaluation, and treatment of neonatal hypoglycemia. Glucose homeostasis in the fetus and neonate is a developmentally regulated dynamic process involving a number of intricate physiologic mechanisms. In addition, the determination of glucose concentrations is dependent upon both the type of tissue analyzed and the limitations of the specific method employed. The complexity of glucose metabolism makes it difficult to precisely define "normal" and "abnormal" glucose levels in preterm and term neonates.

Blood Glucose↗

Rhesus isoimmunization: increased hemolysis during early infancy.

The objective of the present study was to determine whether whole blood carboxyhemoglobin (COHb) and plasma bilirubin, two indicators of hemolysis, are elevated in infants with severe Rh isoimmune hemolytic disease during the first months of life. Beginning at 2 wk of age and continuing monthly for 3 mo, serial blood samples were obtained for COHb, plasma bilirubin, Hb, reticulocyte count, plasma erythropoietin, plasma enzymes, and plasma iron. Because control infants (n = 13) and infants with ABO hemolytic disease (n = 5) did not differ from one another in any of the study parameters, these two groups were combined and compared with infants with the Rh isoimmunization. Infants with severe Rh isoimmune hemolytic disease (n = 13) were found to have significantly lower Hb and significantly higher bilirubin, the COHb fraction divided by the Hb concentration (COHb/Hb), and plasma erythropoietin levels at 2 and 6 wk of age, and reticulocyte counts at 6 wk. The remaining parameters were not different between the control-ABO group and Rh-isoimmune group at any of the study intervals. The study's two primary indicators of hemolysis, plasma bilirubin and COHb/Hb, were significantly correlated with one another in the Rh-immunized group (r = 0.66, p < 0.0001), but not in the combined control-ABO group. Serial Rh antibody concentrations measured in the serum of four neonates with Rh isoimmunization demonstrated a mean half-life of 14.3 d. We speculate that, among infants with severe Rh isoimmune hemolytic disease, elevated total bilirubin levels and COHb/Hb ratios identified in the early weeks of life indicate continuing hemolysis due to persistence of maternal Rh antibodies.

ABO Blood-Group System↗

The value of neurophysiologic approaches in the anticipation and evaluation of neonatal hypoglycemia.

The association of low blood glucose with central nervous system (CNS) injury was first described in 1937 by Hartmann and Jaudon. In the early 60 years since publication of these observations the effects of hypoglycemia upon the brain remain poorly understood. Technology capable of accurately determining plasma glucose concentrations has been developed. Investigators have sought to establish critical values below which glucose levels should not be allowed to fall. Despite these efforts the definitive level of glucose capable of producing brain injury in any particular patient remains unknown. Glucose homeostasis within the neonatal CNS represents a dynamic process consisting of many interrelated variables including gestational and chronologic age, genotype, relative health, blood flow, metabolic rate and availability of other suitable substrates. New technique for assessing the glucose delivery: consumption ratio and directly monitoring the cellular consequences of glucose deprivation within discrete regions of the brain will help to answer the question 'How long is too low and how long is too long?'

Blood Glucose↗

Ontogeny of heme oxygenase activity in the hippocampus, frontal cerebral cortex, and cerebellum of the guinea pig.

Heme oxygenase (HO) catalyzes the oxidation of heme to produce carbon monoxide (CO), biliverdin and iron. CO is considered to function as a novel neuronal messenger in the brain analogous to nitric oxide. The ontogeny of microsomal HO activity in the hippocampus, frontal cerebral cortex, and cerebellum of the immature fetal, mature fetal and adult guinea pig was determined using an optimized assay which quantitated heme-derived CO formation by a gas chromatographic method. There was a distinct developmental profile of HO activity that was similar for all three brain regions. In particular, HO activity was maximal in the mature fetus compared with the immature fetus and the adult. These data demonstrate that HO activity is developmentally regulated and that there is similar ontogeny of HO activity in the hippocampus, frontal cerebral cortex, and cerebellum of the guinea pig.

Aging↗

The risk of carbon monoxide poisoning after prolonged laparoscopic surgery.

OBJECTIVE: To evaluate whether thermal energy produced by laser and bipolar electrosurgery during laparoscopic procedures significantly elevates blood carboxyhemoglobin levels. METHODS: We prospectively studied 27 healthy nonsmoking patients, mean +/- standard deviation (SD) age 39.1 +/- 8.0 years (range 22-56), scheduled for laparoscopic procedures in which smoke was generated. Prolonged operative laparoscopy involved high-flow carbon dioxide insufflation, intensive evacuation of intra-abdominal smoke, and controlled hyperventilation with 50-100% oxygen. Laser and bipolar electrosurgery were used in all cases. Blood samples were drawn before and after surgery. Carboxyhemoglobin concentrations were measured using a highly accurate gas chromatography method. RESULTS: The mean +/- SD duration of surgery was 141 +/- 72 minutes (range 45-300). The mean +/- SD carboxyhemoglobin levels were 0.70 +/- 0.15% (range 0.44-1.20%) before surgery and 0.58 +/- 0.20% (range 0.30-1.33%) after surgery. A significant decrease (P < .001) in carboxyhemoglobin concentrations occurred during surgery (mean +/- SD, 20 +/- 11%; range 3-46%). The carboxyhemoglobin level was increased at the end of surgery in only one woman. In only one patient did the levels exceed 1% (1.33%), still well below the human threshold tolerance level of 2%. The Spearman correlation coefficient between carboxyhemoglobin concentrations and duration of surgery was r = 0.308 (P = .12). CONCLUSION: Carbon monoxide (CO) poisoning is not associated with even prolonged laparoscopic surgical procedures. This may be attributed to aggressive smoke evacuation that minimizes exposure to CO, and to active elimination of CO by ventilation with high oxygen concentrations.

Adult↗

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↗

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↗

Contribution of haemolysis to jaundice in Sephardic Jewish glucose-6-phosphate dehydrogenase deficient neonates.

We determined the contribution of haemolysis to the development of hyperbilirubinaemia in glucose-6-phosphate dehydrogenase (G-6-PD) deficient neonates and G-6-PD normal controls. Blood carboxyhaemoglobin (COHb), sampled on the third day of life, was measured by gas chromatography, corrected for inhaled carbon monoxide (COHbC), and expressed as a percentage of total haemoglobin concentration (Hb). Serum bilirubin was tested as clinically necessary. 37 non-jaundiced (peak serum total bilirubin (PSTB) < or = 255 mumol/l) and 20 jaundiced (PSTB > or = 257 mumol/l) G-6-PD-deficient neonates were compared to 31 non-jaundiced and 24 jaundiced controls with comparable PSTB values, respectively. COHbC values for the entire G-6-PD deficient group were higher than in the controls (0.75 +/- 0.17% v 0.62 +/- 0.19%, P < 0.001). COHbC and PSTB values did not correlate in the G-6-PD-deficient group (r = 0.15, P > 0.05) but did in the controls (r = 0.58, P < 0.001). COHbC values were increased to a similar extent in the G-6-PD-deficient, non-jaundiced (0.72 +/- 0.16%), the G-6-PD-deficient, jaundiced (0.80 +/- 0.19%) and the control, jaundiced (0.75 +/- 0.18%) subgroups, compared to the control, non-jaundiced subgroup (0.53 +/- 0.13%) (P < 0.05). Although present in G-6-PD deficient neonates, increased haemolysis was not directly related to the PSTB.

Carbon Monoxide↗

Intravenous immune globulin in neonatal immune hemolytic disease: does it reduce hemolysis?

We studied the effect of intravenous immune globulin (IVIG) on hemolysis in term, hyperbilirubinemic, Coomb's positive infants utilizing measurement of carboxyhemoglobin fraction corrected for inhaled carbon monoxide (COHbc), a sensitive indicator of hemolysis. COHbc values were determined before and after IVIG infusion. In those babies who responded with a decrease in serum total bilirubin (n = 19), no exchange transfusions were required and COHbc levels decreased significantly by 24 h post-IVIG from 1.37 +/- 0.31 to 1.12 +/- 0.26% tHb (p < 0.0001). There were no corresponding decreases in COHbc levels (1.989 +/- 0.54 to 1.82 +/- 0.48% tHb; p > 0.05) among those whose serum bilirubin levels did not decrease in response in to IVIG (n = 7), and all of these infants required exchange transfusions. Furthermore, the extent of the decrease in COHbc was related to the degree of decrease in serum bilirubin levels, such that the percentage decrease of bilirubin at 24 h was directly correlated with the percentage decrease of COHbc at 24 h (p = 0.007). We conclude that IVIG, when successful, inhibits hemolysis in these infants.

Erythroblastosis, Fetal↗

Neonatal intracranial ischemia and hemorrhage: diagnosis with US, CT, and MR imaging.

PURPOSE: To assess the usefulness of ultrasound (US), computed tomography (CT), and magnetic resonance (MR) imaging in the detection of intracranial hemorrhage and ischemia in newborns. MATERIALS AND METHODS: Seventy-six neonates who underwent US within 72 hours of CT or MR examination were studied. Four observers rated images for the presence of germinal matrix hemorrhage (GMH), intraventricular hemorrhage (IPH), extraaxial hemorrhage, and hypoxic-ischemic encephalopathy. RESULTS: In 39% of neonates, CT and MR imaging provided greater confidence than US for the diagnosis or exlusion of neonatal ischemia or hemorrhage. Kappa analysis revealed significantly better interobserver agreement with CT than with US for the detection of GMH, IVH, IPH, and cortical infarction or ischemia (P <.005). Interobserver agreement was significantly better with MR imaging than with US for the detection of GMH, IVH, and cortical infarction or ischemia (P < .005). CONCLUSION: Sensitivity and interobserver agreement are better with MR imaging and CT than with US for the detection of neonatal cortical ischemia or infarction.

Apgar Score↗

Intravenous immune globulin in neonatal ABO isoimmunization: factors associated with clinical efficacy.

OBJECTIVE: Intravenous immune globulin (IVIG) reduces jaundice in many but not all cases of neonatal isoimmunization. We sought to elucidate the type of infant most likely to benefit from IVIG administration by attempting to define pretreatment parameters associated with both clinical symptomatology and therapeutic responsiveness to IVIG. METHODS: Term, healthy Coombs-positive infants were studied prospectively. IVIG was administered if, despite phototherapy, serum bilirubin reached > or = 222 mumol/l (13 mg/dl) at < or = 24 h of age and/or > or = 274 mumol/l (16 mg/dl) at > 24 h of age. Clinical data including serial serum total bilirubin levels, rate of bilirubin rise on day 1 of life, serial corrected carboxyhemoglobin levels (a sensitive indicator of hemolysis) and total hemoglobin (tHb) levels were collected. RESULTS: Infants were classified as IVIG responders (n = 18), those in whom total serum bilirubin levels either remained stable or decreased following IVIG administration; IVIG nonresponders (n = 5), those who developed a total serum bilirubin of > or = 2 mg/dl greater than pre-IVIG bilirubin levels within the first 24 h after IVIG administration, or nontreated, those not meeting IVIG treatment criteria (n = 13). Four of the five nonresponders proceeded to require exchange transfusion vs. none of the others (p < 0.001). Four of the five nonresponders had a pretreatment rate of bilirubin rise of > or = 1 mg/dl/h as compared with only 1 of 18 responders and none of the nontreated (p < 0.001). Pretreatment tHb levels were also different (13.2 +/- 1.3 vs. 15.5 +/- 2.3 vs. 17.7 +/- 2.4 g/dl for nonresponders vs. responders vs. nontreated infants, respectively; p < 0.005). The highest pretreatment COHbc levels were seen in the nonresponders (1.8 +/- 0.7 vs. 1.4 +/- 0.3 vs. 0.9 +/- 0.3% tHb, respectively). CONCLUSIONS: Our 3 groups represent a spectrum of hemolysis, ranging from severe to moderate to mild. This spectrum appears to relate not only to the severity of hemolysis, but also to the therapeutic responsiveness to IVIG. We speculate that some or all of the factors identified can be used prospectively to predict the subsequent clinical course of ABO-incompatible infants and to facilitate optimal management.

ABO Blood-Group System↗

Imaging brain injury using time-resolved near infrared light scanning.

Conventional brain imaging modalities are limited in that they image only secondary physical manifestations of brain injury, which may occur well after the actual insult to the brain and represent irreversible structural changes. A real-time continuous bedside monitor that images functional changes in cerebral blood flow or oxygenation might allow for recognition of brain tissue ischemia or hypoxia before the development of irreversible injury. Visible and near infrared light pass through human bone and tissue in small amounts, and the emerging light can be used to form images of the interior structure of the tissue and measure tissue blood flow and oxygen utilization based on light absorbance and scattering. We developed a portable time-of-flight and absorbance system which emits pulses of near infrared light into tissue and measures the transit time of photons through the tissue. Images can then be reconstructed mathematically using either absorbance or scattering information. Pathologic brain specimens from adult sheep and human newborns were studied with this device using rotational optical tomography. Images generated from these optical scans show that neonatal brain injuries such as subependymal and intraventricular hemorrhages can be successfully identified and localized. Resolution of this system appears to be better than 1 cm at a tissue depth of 5 cm, which should be sufficient for imaging some brain lesions as well as for detection of regional changes in cerebral blood flow and oxygenation. We conclude that light-based imaging of cerebral structure and function is feasible and may permit identification of patients with impending brain injury as well as monitoring of the efficacy of intervention. Construction of real-time images of brain structure and function is now underway using a fiber optic headband and nonmechanical rotational scanner allowing comfortable, unintrusive monitoring over extended periods of time.

Animals↗

Duration of action and tissue distribution of zinc protoporphyrin in neonatal rats.

Zinc protoporphyrin IX (ZnPP) has been shown to inhibit heme oxygenase (HO) activity effectively in vivo and has potential in the treatment of neonatal jaundice. Because this is a transitional or temporary condition lasting only several days, an effective chemopreventive agent with a relatively short duration of action would be desirable for the treatment of severe neonatal jaundice. To determine the effective duration of action of ZnPP, we administered either 40 nmol/g of body weight ZnPP or 5 microL/g body weight diluent intraperitoneally to neonatal rats 24-36 h after birth. Between 0 and 21 d after ZnPP dosing, the duration of action was investigated through measurements of serum bilirubin and hepatic and splenic HO inhibition, which were correlated to measurements of ZnPP distribution. Significant (p < 0.05) hepatic HO inhibition, ranging from 27 to 51%, was observed in the liver between 1 and 4 d after dosing, concurrent with a 23-28% reduction in serum bilirubin levels, and was associated with ZnPP tissue concentrations of 27-38 nmol/g. Splenic HO was not inhibited measurably by the much lower concentrations of ZnPP found in the spleen (2.8-20.1 nmol/g) between 0 and 21 d after dosing. Furthermore, HO isoform 1 (HO-1) induction was apparently not a confounding factor in the duration of action of ZnPP, because the modest increases in HO-1 protein levels were not sustained longer than 24 h after ZnPP administration. Our findings demonstrated that the duration of action of ZnPP in neonatal rats is less than 1 wk. The reduction in serum bilirubin levels, the short duration of action and minimal confounding effects suggest that ZnPP may be an effective chemopreventive agent for the treatment of severe neonatal jaundice.

Animals↗

Hepatic heme oxygenase is inducible in neonatal rats during the early postnatal period.

Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme to bilirubin. Cobalt chloride (CoCl2) and many other agents that generate oxidant stresses induce the HO-1 isoform. Furthermore, HO-1 has been shown to protect against oxidant stress in vitro and in vivo by mechanisms involving increased ferritin synthesis. However, little is known about the inducibility of hepatic HO-1 during the very early postnatal period, and whether HO-1 induction is associated with increased ferritin synthesis in neonates. Therefore, we studied hepatic HO-1 mRNA, HO-1 protein concentration, total HO activity, and ferritin protein levels in neonatal rats. Neonatal rats 0-5 d of age were injected with 250 mumol/kg body weight of CoCl2. 6H2O in saline or with an equal volume of saline in age-matched controls. Liver samples were collected 4 h after injection for HO-1 mRNA analysis and 20 h after injection for analysis of HO-1 protein concentration, total HO activity, and ferritin protein levels. In CoCl2-treated rats, hepatic HO-1 mRNA was 3-10 times the levels in control rats (p < 0.05), HO-1 protein concentration was 2-5 times the levels in control rats (p < 0.05), and total HO activity was higher by 20-80% than in control rats (p < 0.05). There were no differences in hepatic ferritin protein levels between CoCl2-treated neonatal rats and controls; however, in CoCl2-treated adult rats, hepatic ferritin protein levels were 1.6 times the levels in controls (p < 0.05). Thus, neonatal rats can up-regulate hepatic HO-1 mRNA, HO-1 protein concentration, and total HO activity in response to CoCl2; however, no upregulation of hepatic ferritin protein levels was observed in neonatal rats after CoCl2 administration or subsequent HO-1 induction. We speculate that neonatal rats induce hepatic HO-1 and up-regulate ferritin by different mechanisms than do adult rats.

Adaptation, Physiological↗