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Biomedical subjects

C L Kien

Publications and source records attributed to C L Kien.

At least 37 records · Page 2Linked to original sources

A portable device for estimating the rate of CO2 production in preterm infants.

We developed a simple flow-through system for measuring the net rate of pulmonary excretion of CO2 (VCO2). Its components, connected in series by plastic tubing, are the following: plastic oxygen hood, suction flask used both as a mixing and sampling chamber, Brooks mass flow controller, and wall suction. Gas aliquots withdrawn from the sampling flask are analyzed for CO2 concentration in the laboratory. The system was validated by measuring over a 60-min period the evolution of CO2 from the reaction of sodium carbonate with phosphoric acid. In 9 trials, the mean recovery of CO2 was 99.8%. In 14 studies in 11 preterm infants, we evaluated the reproducibility of duplicate measurements of CO2 production on consecutive days; in 9 of the studies, the coefficient of variation was < 5%, but in other 5 studies, it ranged from 7.7 to 35.8%. We believe that this device might have both research and clinical applicability.

Carbon Dioxide↗

Elevated hepatic glucose production in children with cystic fibrosis.

We hypothesized that elevated hepatic glucose output (HGO) may occur in children with cystic fibrosis (CF) as an early sign of declining insulin secretion and that tolbutamide therapy would correct the defect. We studied eight glucose-tolerant CF patients (mean +/- SD, 9.1 +/- 1.9 y) and five healthy controls (9.0 +/- 1.6 y). Fasting glucose, insulin, and insulin-connecting peptide concentrations were not different in the CF and control subjects; however, meal stimulation tests in the CF patients suggested that insulin secretion was defective in the fed state. HGO (mg.kg-1 body weight.min-1) was 26% higher in the CF patients (4.2 +/- 0.7 versus 3.1 +/- 0.6 in HC) (p = 0.016). When normalized for fat-free mass (mg.kg fat-free mass-1.min-1), HGO was 27% higher in CF (4.9 +/- 0.8 versus 3.8 +/- 0.5) (p = 0.015). However, when expressed as a function of resting energy expenditure (mg.kcal-1), HGO was not significantly different in CF (121 +/- 22) versus healthy controls (116 +/- 30). In seven of the CF group, HGO was re-assessed after a 2-h glucose infusion at a rate of 0.90 +/- 0.02 mg.kg-1.min-1. HGO was suppressed (p < 0.05) by an amount equal to 103 +/- 18% of the glucose infusion rate. Finally, in five CF patients, HGO was re-measured after 2 wk of oral therapy with tolbutamide (750 mg/d). Tolbutamide did not affect HGO (fasting or during the glucose infusion). In conclusion, fasting HGO was elevated in the CF patients in proportion to energy expenditure.

C-Peptide↗

Energy expenditure in adolescents during low intensity, leisure activities.

We sought to determine how a stationary activity such as playing a stringed instrument may affect energy expenditure (EE) in adolescents. Using automated indirect calorimetry, we measured EE in eight adolescents (1 male, 7 females, 14.2 +/- 2.1 yr) while they each performed the following activities: watching television (TV) (60 min), playing a stringed instrument (60 min), and walking at 40% of peak oxygen uptake (43 min). Measurements were made during three, 6- to 7-min steady state periods of each activity. EE (mean +/- SD) was lower during TV (1.0 +/- 0.2 kcal.min-1) and instrument playing (1.4 +/- 0.2 kcal.min-1) than during walking (3.4 +/- 0.4 kcal.min-1) (P < 0.05). EE during instrument playing was 41% greater than during television viewing (P < 0.05). We conclude that relatively sedentary activities such as playing a stringed instrument can elevate EE. Conceivably, other stationary, leisure activities performed by adolescents may increase EE and have substantial, cumulative effects on long-term energy balance and fat accretion.

Adolescent↗

Comparison of methods for estimating fecal carbohydrate excretion in premature infants.

Our previous studies have suggested that there is minimal fecal excretion of carbohydrate-derived energy in premature infants fed lactose or glucose-polymer as the source of carbohydrate. In these studies, carbohydrate energy excretion was equated with the non-nitrogenous, nonfat energy. Although these studies provided consistent results, this methodological approach cannot distinguish actual excretion of dietary carbohydrate from carbohydrate in the form of large molecular compounds derived from infant or bacterial cells (which in fact comprise approximately 90% of the measured value). Therefore, in this study we compared the absorption of carbohydrate energy to the fractional absorption of 13C derived from [D-1-13C]-lactose in 10 premature infants 30-32 weeks gestational age fed either a commercial premature infant formula containing a mixture of carbohydrates (50% lactose: 50% glucose polymer) or the same formula in which lactose was the sole carbohydrate. The two methods provided comparable estimates of carbohydrate absorption (96 and 94%, respectively), although there were significant discrepancies in two infants. These studies provide evidence of external validity for the two methods.

Carbohydrate Metabolism↗

Isotopic estimation of CO2 production during exercise before and after endurance training.

Endurance training reduces the rate of CO2 release (i.e., VCO2) during submaximal exercise, which has been interpreted to indicate a reduction in carbohydrate oxidation. However, decreased ventilation, decreased buffering of lactate, and/or increased fixation of CO2 could also account for a lower VCO2 after training. We therefore used a primed continuous infusion of NaH13CO3 to determine the whole body rate of appearance of CO2 (RaCO2) in seven men during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2peak) before and after endurance training. RaCO2 is independent of the above-described factors affecting VCO2 but may overestimate net CO2 production due to pyruvate carboxylation and subsequent isotopic exchange in the tricarboxylic acid cycle. Training consisted of cycling at 75-100% VO2peak for 45-90 min/day, 6 days/wk, for 12 wk and increased VO2peak by 28% (P < 0.001). VCO2 during submaximal exercise was reduced from 86.8 +/- 3.7 to 76.2 +/- 4.2 mmol/min, whereas RaCO2 fell from 88.9 +/- 4.0 to 76.4 +/- 4.4 mmol/min (both P < 0.001). VCO2 and RaCO2 were highly correlated in the untrained (r = 0.98, P < 0.001) and trained (r = 0.99, P < 0.001) states, as were individual changes in VCO2 and RaCO2 with training (r = 0.88, P < 0.01). These results support the hypothesis that endurance training decreases CO2 production during exercise. The magnitude and direction of this change cannot be explained by reported training-induced alterations in amino acid oxidation, indicating that it must be the result of a decrease in carbohydrate oxidation and an increase in fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stable isotope model for estimating colonic acetate production in premature infants.

In premature infants, a nutritionally significant proportion of lactose is apparently fermented in the colon to acetate. To estimate the rate of entry of acetate into the peripheral circulation, a model that takes into account extraction of gut-derived acetate by splanchnic and hepatic tissues was developed. Using a [1-13C]acetate orogastric infusion technique, six studies were carried out on five premature infants during constant orogastric feeding. Ranges in gestational age, postnatal age, and breath H2 concentration (corrected for CO2 content) were 28-32 weeks, 16-29 days, and 45-252 microL/L, respectively. The estimated rate of entry of acetic acid (mean +/- SD) was 63.7 +/- 33.8 mumol.kg-1.min-1 (range, 22.9-123.2 mumol.kg-1.min-1), which corresponded to 64.3% +/- 38.6% (24%-136%) of the potential two carbon units from dietary lactose. Thus, a substantial fraction of dietary lactose in premature infants may be converted to acetic acid; this conversion could have a significant effect on protein as well as energy requirements.

Acetates↗

Efficient assimilation of lactose carbon in premature infants.

Previous studies have shown that there is minimal fecal excretion of carbohydrate energy in premature infants with high breath H2 concentrations, implying that the colon plays an important role in salvaging lactose energy. The present study extends this work by using a stable isotope method for serial assessment of lactose carbon excretion. Thus, in nine premature infants (30-32 weeks of gestation and 11-36 days of age), we conducted 23 longitudinal studies of breath hydrogen concentration and the cumulative fecal excretion of 13C derived from a single dose of [D-1-13C]lactose. The ranges of values (mean +/- SD) for breath hydrogen concentration and lactose absorption were respectively 4-440 ppm/5% CO2 (92 +/- 100) and 82-100% tracer dose (98.4 +/- 3.9). In 21 studies, lactose carbon excretion was less than 2% of the dose. There was a significant correlation between postnatal age and breath hydrogen concentration (R = 0.48; p = 0.02). These studies suggest that colonic fermentation activity is adequate for efficient colonic salvage of lactose even during the second week of life.

Breath Tests↗

In vivo estimation of lactose hydrolysis in premature infants using a dual stable tracer technique.

To investigate their putative capacity for lactose digestion, primed continuous orogastric infusions of [1-13C]glucose and D-[1-13C]lactose were administered on consecutive days to five premature infants (30-31 wk gestation, 15-32 days of age), who were fed by orogastric infusions of human milk or formula. By monitoring the plateau isotopic enrichment of plasma glucose using isotopomers containing the entire derivatized glucose molecule or C-2 through C-6, we were able to distinguish label appearing in the peripheral circulation deriving from unmetabolized glucose from that arising from recycled or fermented glucose (or lactose). Isotopic enrichment of the C-1 of glucose, corrected for recycling, was then calculated during each tracer infusion, and the fraction of dietary lactose subjected to in vivo hydrolysis was estimated from these values and the respective tracer infusion rates, assuming similar absorptive and metabolic fates of labeled glucose arising from either tracer. This fraction averaged 1.02 +/- 0.16 (SD), suggesting that lactose digestion is efficient by 34-wk postconceptional age.

Bicarbonates↗

Effects of tolbutamide on growth and body composition of nondiabetic children with cystic fibrosis.

Previously, we reported that nondiabetic children with cystic fibrosis show a blunted insulin response to a meal stimulus. In the study presented here, using tolbutamide, we determined the effects of augmented insulin secretion/action on height and lean body mass of children with cystic fibrosis. Twelve subjects (mean +/- SEM age, 11.0 +/- 0.5 y) were studied for three 4-mo periods: 1) pretreatment, 2) treatment, consisting of 750 mg/d of tolbutamide, and 3) posttreatment. Before the pretreatment period, insulin response to a meal stimulus was evaluated in relation to three doses of tolbutamide: 0, 250, and 500 mg. Growth was monitored during each period, and incremental changes in lean body mass were calculated from height data. To validate the change in lean body mass based on height measurements, we determined lean body mass in seven subjects during the treatment period by using a criterion method (H218O). Growth velocity (cm/4 mo) significantly increased (p less than 0.05) during the treatment (2.58 +/- 0.31) compared with the pretreatment period (0.88 +/- 0.20). The increase in lean body mass calculated from height was greater during the treatment (1.61 +/- 0.29 kg/4 mo) than during the pretreatment period (0.44 +/- 0.18 kg/4 mo) (p less than 0.05). There was also a significant increase (p less than 0.05) in lean body mass during the treatment as measured with H218O (1.91 +/- 0.65 kg/4 mo). Acute administration of either 250 or 500 mg of tolbutamide reduced (p less than 0.05) the area under the glucose concentration curve in response to a meal compared with the control condition of no tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of glucose infusion on leucine transamination and oxidation in the ovine fetus.

During fasting of the ewe, the rate of amino acid oxidation by the ovine fetus increases substantially. We hypothesized that the increase in amino acid oxidation derived mainly from reduced protein synthesis. We further hypothesized that fetal glucose supplementation would result in diminished amino acid oxidation. To test these hypotheses, nine ovine fetuses were infused with [15N,1-13C]leucine to determine the rates of leucine appearance and disposal. Simultaneously, the fetal uptake of leucine was determined. Animals were studied in the fed and fasted state. After baseline measurements, glucose was infused into the fetal inferior vena cava at a rate estimated to match the fetal glucose uptake. Results of these studies indicate that leucine nitrogen flux, leucine carbon flux and fetal leucine uptake were constant. Leucine oxidation was increased by 50% in the fasted state (6.3 versus 13.4 mumol/min); glucose infusion resulted in a 25% decline in oxidation (to 10.4 mumol/min) in the fasted state, but had no effect in the fed state. Mean leucine umbilical uptake during fasting was 9.3 mumol/min, 4.1 mumol/min less than leucine oxidation. These data suggest that leucine (and potentially other amino acids) may be in negative balance during maternal fasting, and can be spared by supplementation of the fetus with exogenous glucose.

Animals↗

Measurement of stable isotopic enrichment of underivatized acetate by gas chromatography/mass spectrometry: application to in vivo estimation of acetate production.

In order to assess endogenous and colonic production of acetate, we have developed an assay for determining the isotopic enrichment of plasma acetate using gas chromatography/mass spectrometry (GC/MS). Acidified, deproteinized plasma (200 microliters) was extracted into ethyl ether, and the ether phase was then injected into a gas chromatograph/mass spectrometer fitted with a 30 m x 0.252 mm i.d. capillary column (temperature program 50-245 degrees C at 10 degrees C min-1). Using electron impact GC/MS and selected ion monitoring, peak areas of ions with m/z 60 and 61 (M + 1) were determined. Triplicate extractions of enriched plasma samples (mol.% excess 1.38-1.5%) resulted in a coefficient of variation of 1.6-5.9%. Unenriched plasma samples were found to have an enrichment close to theoretical natural abundance, and analysis of our (1-13C)acetate tracer (99 at.% excess) revealed an ion at m/z 61 and no ion at m/z 60. To verify accuracy, we conducted an in vivo isotope dilution study. In a 1-month-old piglet, fasted for 24 h, changing the rate of a 4 h infusion (mmol h-1) of (1-13C)acetate from 0.141 to 0.282 doubled the isotope enrichment (2.08 x) of the second plateau. The rate of appearance of acetate was 26.0 mumols kg-1 min-1, which is comparable to that reported in fasting sheep.

Acetates↗

Contribution of low-molecular-weight compounds to the fecal excretion of carbohydrate energy in premature infants.

It was hypothesized that low-molecular-weight products of carbohydrate fermentation would contribute only a small percentage to the total fecal excretion of nonfat, nonnitrogenous energy (carbohydrate energy) in premature infants. Infants born at 28-32 weeks' gestation who were 2-4 weeks of age were randomized to receive a formula with lactose as the sole carbohydrate (n = 7) or the same formula with 50% of the carbohydrate as glucose polymer (n = 8). The percent contribution (X +/- SD) to total carbohydrate energy of sugars (glucose, galactose, lactose, glucose polymer), short-chain fatty acids (acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate), and D- and L-lactate was 9.4% +/- 2.9% for the 15 subjects and was not significantly different between groups. The percent contribution of all four sugars was 5.8% +/- 1.7% and did not differ between the two groups. Doubling the lactose intake resulted in significant increases in fecal excretion (kilocalories per kilogram per day) of acetate (77% increase; P = 0.03), total short-chain fatty acids (54%; P = 0.04), and galactose (188%; P = 0.03). These data suggest that as much as 90% of fecal carbohydrate energy may be in the form of large-molecular-weight compounds, presumably bacterial in origin.

Dietary Carbohydrates↗

A metabolic bed for collecting excreta in premature infants.

A mattress and plastic bed for collection of urine and feces in premature infants housed in isolettes is described. The dimensions of the bed are 65.5 x 34.4 x 13.5 cm. A drainage hole is located 18 cm from the foot of the bed and midway (16.5 cm) from either side. The angle of the depression in the bed for the drainage hole is approximately 12.5 degrees. The bed is covered with a plastic-backed foam rubber mattress. The plastic surface on which the infant lies is impervious to water. The method of excreta collection using the bed does not involve the need for restraints; urine and/or feces are washed off the undiapered infant and the bed into a container beneath the drainage hole. The bed has been well tolerated in over 30 studies of 4 days duration, and laboratory experiments with urine and feces applied to the mattress for 15-60 min have indicated excellent recovery of total nitrogen.

Beds↗

Isotopic dilution of CO2 as an estimate of CO2 production during substrate oxidation studies.

The rate of oxidation of a substrate is often divided by the numerical estimate of a correction factor for the proportion of labeled CO2 that is excreted during the course of the experiment. This factor, derived from tracer studies of bicarbonate kinetics, equals the product of the net rate of respiratory CO2 excretion and the ratio of the plateau isotopic enrichment of CO2 to the rate of infusion of labeled bicarbonate. The inverse of this ratio may be equated to the rate of appearance of unlabeled CO2. When one substitutes the expression for the correction factor into a typical equation for the rate of substrate oxidation, the rate of appearance of CO2 substitutes for both net CO2 excretion and the correction factor in the original oxidation equation. Thus the rate of appearance of CO2 is an index of CO2 production that takes into account both net fixation of CO2 and isotopic exchange of labeled CO2; it also may have application as an index of net CO2 production.

Animals↗

Digestion, absorption, and fermentation of carbohydrates.

Newborn infants born after a term gestation appear to have an adequate capacity for small intestinal digestion and absorption of carbohydrate. Premature infants do not have a mature level of intestinal lactase activity. Apparently, in the premature infant, colonic fermentation serves an important, if not the only major route, for lactose carbon absorption, and it also appears that signs of fermentation activity such as increased BH2 are not indicative of disease. Important questions remaining in the premature infant relate to developmental aspects of colonic fermentative activity, effects of systemic antibiotic treatment on colonic salvage, the effects of various fermentation pathways on energy balance, the capacity for absorption of sugars, SCFA, and electrolytes by colonic epithelia, and the effects of fermentation products on metabolism and on the mucosal cells of the intestine or colon. Research addressing these questions may have relevance in the following areas: further development of formula diets for healthy premature infants and for patients of all ages with intestinal or colon dysfunction; the effects of colonic disease or surgical resection; the nutritional or clinical effects of dietary fiber; and the effects of antibiotic therapy on intestinal and colon function.

Animals↗