Clinton R. Ostrander

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production

A total of 45 infants, including 20 appropriate-size-for-gestational-age infants (AGAs), 19 large-size-for-gestational-age infants (LGAs) and 6 infants of diabetic mothers (IDMs), had determinations of their pulmonary excretion rate of carbon monoxide (VeCO) in the first postnatal week as an index of bilirubin production. We calculated a ratio (Rw) of birth weight to ideal weight (50th percentile for gestational age) as a relative measure of infant size. We also measured maternal glycosylated hemoglobin (Hb AIc) in the postpartum period as a reflection of the time-integrated blood glucose level over the weeks preceding delivery. Mean values for maternal Hb AIc in the postpartum period, infant Rw, and VeCO were all significantly increased for the LGAs and IDMs compared to the normal AGAs. Nine LGAs had mothers whose Hb AIc levels were >2 S.D. higher than the mean Hb AIc level for mothers of normal AGAs. The infants whose mothers had the highest Hb AIc levels were not always the ones with the highest bilirubin production rates. These findings suggest that maternal Hb AIc in the postpartum period, infant size, and bilirubin production are associated phenomena, but that a postpartum time-integrated measure of blood glucose level over the weeks preceding parturition may not reflect changes in other associated factors which can affect infant erythropoiesis. The LGAs are not a homogeneous group, and some may have mothers with missed abnormalities of gestational glucose metaoblism.

Breath hydrogen analysis: a review of the methodologies and clinical applications.

Hydrogen gas (H2) is a product of the fermentation of dietary carbohydrate (CHO) by bacteria in the lumen of the gastrointestinal tract in man. Thus, H2 is actually an exogenously produced gas, which either is passed as flatus, or diffuses into the body and is exhaled. In the adult, a fairly constant fraction is expired, providing a reliable indicator of total colonic H2 production. Breath H2 analysis currently represents a useful clinical means of testing adults and older children for the malabsorption of CHO. Noninvasive and easy procedures for the collection of expired air have encouraged their increasingly widespread use in pediatrics. Evidence to date suggests that breath H2 analysis may provide the best available method for estimating semiquantitatively the degree of CHO malabsorption. The association of the results of breath H2 analysis with other clinical measures of CHO digestion and absorption is expected, but discrepancies can also be anticipated based on the nature of this particular trace gas method. The interpretation of the results of breath H2 analysis in neonates and young infants remains especially problematic because of confounding variables which are difficult to control and are measured infrequently.

Neonatal Bilirubin Production Estimated from “End-Tidal” Carbon Monoxide Concentration

The relationship between the pulmonary excretion rate of carbon monoxide (VECO) and the concentration of CO, in a sample of breath, drawn through a nasopharyngeal catheter at end-expiration, was assessed in 25 studies of nine preterm and 14 term infants. The VECO and this approximate end-tidal sample of CO (ETCO) correlated significantly over a wide range of CO elimination rates: VECO = 10.45 ETCO + 2.25 (n = 25, r = 0.95). The ETCO correctly predicted elevations in VECO > 2 SD of the mean VECO for normal infants (13.9 ± 3.5 μl/kg/h), with 90% sensitivity and 73% specificity (p < 0.01). Three subjects with Rh isoimmune hemolytic disease were easily identified by the ETCO as well as the VECO. The ETco is a simple, noninvasive measurement for rapidly identifying infants with significant hemolytic disease.

Pulmonary Excretion Rates of Carbon Monoxide Using a Modified Technique: Differences between Premature and Full-Term Infants

The pathophysiology of the exaggerated hyperbilirubinemia in premature infants remains unclear. The relative contribution of bilirubin production may be estimated by measuring the pulmonary excretion rate of carbon monoxide (VeCO). We found that the mean VeCO of premature infants, 16.7 +/- 5.0 microliters/kg/h, was significantly elevated (p less than 0.05) compared with the mean VeCO of full-term infants, 13.9 +/- 3.5 microliters/kg/h. Premature infants who required phototherapy had a significantly (p less than 0.05) higher mean VeCO than those who did not. The VeCO did not correlate with gestational age, implying that factors which associate frequently but variably with gestational age may have an important influence on heme catabolism.

A Sensitive Analytical Apparatus for Measuring Hydrogen Production Rates. II. Application to Studies in Human Infants

We estimated hydrogen (H2) production by determining simultaneously the end-tidal concentration (ETH2) and the direct pulmonary excretion rate (VeH2) in normal-sized, healthy, term and preterm neonates between 2 days and 7 weeks of life who were receiving all their calories enterally as breast milk or a proprietary formula. We found that there was no peak or pattern in H2 production during the first 3 postprandial hours (mean VeH2 = 1.00 +/- 0.97 SD ml/kg/h; mean ETH2 = 40.3 +/- 33.1 SD ppm). Frequently, there was marked short-term variability of the ETH2 in a given infant (coefficient of variation = 13.4% +/- 18.7%). H2 production was elevated in normal neonates without signs of malabsorption. We found that VeH2 correlated with ETH2 using both nasopharyngeal catheter (r = 0.63; p less than 0.001) and nasal prong (r = 0.71; p less than 0.001) collection techniques. We conclude that breath hydrogen determinations in neonates are not readily comparable to similar studies in older patients. Longitudinal studies of individual infants may reveal changes in breath H2 excretion of sufficient magnitude to be distinguishable from moment-to-moment variations, and correlatable with certain intercurrent clinical problems affecting intestinal H2 production or pulmonary H2 excretion. However, interpretation of breath H2 determinations in human infants will be difficult.

A sensitive analytical apparatus for measuring hydrogen production rates. I. Application to studies in small animals. Evidence of the effects of an α-glucosidehydrolase inhibitor in the rat

Abstract A gas analysis and sampling methodology is described for determining total hydrogen excretion rates in Wistar rats. Hydrogen concentrations are evaluated by gas chromatography, using a molecular sieve column connected to a reduction gas detector. Resolution of the analysis is 0.015 ppm hydrogen in a 2.5-ml sample which is 50–100 times more sensitive than previous techniques. Gas samples are obtained by a single-pass (as opposed to rebreathing) method in which hydrogen-free air is passed through glass cylinders containing the experimental animals. Mixing of the animals excreted hydrogen with the chamber flow results in increased hydrogen concentrations at the chamber outlet, from which each animals endogenous production rate can be determined. The method is completely automated and enables multiple studies to be performed simultaneously. As an assessment of the capability of the system to detecting variations in hydrogen production due to carbodydrate malabsorption, 5 male Wistar rats received feeding of both sucrose alone and sucrose plus a known α-glucosidehydrolase inhibitor. In this manner, each animal served as its own control in evaluating the effect of the inhibitor. Administration of sucrose alone resulted in a mean increase in hydrogen production rate of 39% over a 7-h time period, following the initial rise in hydrogen concentration from baseline levels. Administration of sucrose plus inhibitor caused corresponding increases of 95%. Because of the sensitivity and simplicity of the method, it is expected to be a valuable aid in continuing studies of carbohydrate malabsorption of various etiologies.

Pulmonary excretion of carbon monoxide in the human infant as an index of bilirubin production: IIb. Evidence for the possible effect of maternal prenatal glucose metabolism on postnatal bilirubin production in a mixed population of infants

A total of 45 infants, including 20 appropriate-size-for-gestational-age infants (AGAs), 19 large-size-for-gestational-age infants (LGAs) and 6 infants of diabetic mothers (IDMs), had determinations of their pulmonary excretion rate of carbon monoxide (VeCO) in the first postnatal week as an index of bilirubin production. We calculated a ratio (Rw) of birth weight to ideal weight (50th percentile for gestational age) as a relative measure of infant size. We also measured maternal glycosylated hemoglobin (Hb AIc) in the postpartum period as a reflection of the time-integrated blood glucose level over the weeks preceding delivery. Mean values for maternal Hb AIc in the postpartum period, infant Rw, and VeCO were all significantly increased for the LGAs and IDMs compared to the normal AGAs. Nine LGAs had mothers whose Hb AIc levels were >2 S.D. higher than the mean Hb AIc level for mothers of normal AGAs. The infants whose mothers had the highest Hb AIc levels were not always the ones with the highest bilirubin production rates. These findings suggest that maternal Hb AIc in the postpartum period, infant size, and bilirubin production are associated phenomena, but that a postpartum time-integrated measure of blood glucose level over the weeks preceding parturition may not reflect changes in other associated factors which can affect infant erythropoiesis. The LGAs are not a homogeneous group, and some may have mothers with missed abnormalities of gestational glucose metaoblism.

Developmental Changes in Bilirubin Production in the Rat

Total bilirubin production and relative rates of early labeling of bilirubin (ELB) were determined in rats during postnatal development. Total production was estimated by measuring endogenous rate of excretion of carbon monoxide (Veco), while ELB was determined by measuring the incorporation of glycine-2-14C and

CARBON MONOXIDE EXCRETION AS AN INDEX OF BILIRUBIN PRODUCTION IN NEWBORN INFANTS

dT-aminolevulinic acid-5-14C(

1272 RELATIONSHIP OF THE PULMONARY EXCRETION RATE OF CO (VeCO) AND THE BLOOD CARBOXYHEMOGLOBIN LEVEL (COHb) IN PREMATURES AND TERMS

dT-ALA-5-14C) into expired 14CO over a 30-h period after isotope injection. Veco was considerably higher in 1− and 4-day-old rat pups than in adults, but fell rapidly toward adult values by 9 days of age. 14CO excretion from both isotopic precursors of bilirubin was significantly greater in suckling animals than in postweanling and young adult animals when expressed as a percent of the administered radioactivity. The activity of hepatic heme oxygenase showed a similar pattern of postnatal change to 14CO excretion from both glycine-2-14C and