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Biomedical subjects

W W Koo

Publications and source records attributed to W W Koo.

At least 19 recordsLinked to original sources

Validation of accuracy and precision of dual energy X-ray absorptiometry for infants.

There is limited information on the validity of bone mineral content measurement by dual energy X-ray absorptiometry (DXA BMC) for use in subjects with low body mass. We evaluated the accuracy and precision of DXA in piglets (body weight 886-5526 g, median 2096 g). Stepwise multiple regression analyses showed that ash weight is the major determinant of DXA BMC (adjusted r2 = 0.98, RMS residual = 3.61 g). The intercept was not significantly different from zero. DXA BMC measurements of other piglets under various clinical situations showed no significant effect from the use of cotton blanket, diaper, or positioning (prone, supine, lateral). In vivo replication of DXA BMC measurements of infants at a postnatal age of from 1-350 days showed a slope of 0.99 and high correlation coefficient (r2 = 0.99, RMS residual = 3.59 g). The intercept was not significantly different from zero, and the average coefficient of variation of duplicate DXA BMC in infants was 2.8%. We conclude that DXA BMC reliably but proportionately underestimates ash weight and is a highly precise method for measuring bone mineral status in young pediatric subjects.

Absorptiometry, Photon

Technical considerations of dual-energy X-ray absorptiometry-based bone mineral measurements for pediatric studies.

Dual X-ray absorptiometry (DXA) measurements have been shown to provide useful information on bone mineral status in young pediatric subjects. The purpose of this study was to challenge this system under various conditions to determine the clinical and experimental parameters that may be encountered which could interfere with DXA-based bone mineral content (BMC) and bone mineral density (BMD) measurements. Variations in data acquisition, including the covering of step phantom (external calibration standard) with a cotton blanket or partial exclusion of step phantom in the scan field, tissue freezing, or the presence of small nonmetallic objects, did not significantly alter DXA BMC or BMD measurements. By contrast, the presence of movement artifact, radiographic contrast media, and nonmetallic orthopedic casts significantly interfered with DXA BMC and BMC measurements. Variability in operator-dependent analysis of DXA scans occurred with regional analysis of whole body scans for DXA BMC and BMD measurements (average coefficient of variation was 2.9% and 1%, respectively, depending on the region analyzed) but did not affect the total (whole body) result. A minor adjustment in the manual delineation of the step phantom during data analysis may result in almost a 30% difference in DXA BMC and BMD. We conclude that movement artifact, radiographic contrast media, nonmetallic or orthopedic cast, and variations in operator-dependent data analysis may interfere with DXA BMC and BMD measurement in young pediatric subjects. Therefore, appropriate care should be taken to reduce or eliminate such interference.

Absorptiometry, Photon

Plasma mineral concentrations in preterm infants fed a nutrient-enriched formula after hospital discharge.

OBJECTIVE: To determine whether prolonged feeding of preterm infant formula to preterm infants can accelerate recovery to normal plasma zinc levels without affecting plasma mineral homeostasis. DESIGN: Part of concurrent prospective feeding trials in a university hospital-based population. SUBJECTS AND INTERVENTION: Preterm infants (n = 33; birth weight, 1037 +/- 157 gm) were fed a preterm infant formula with higher concentrations of zinc, copper, calcium, magnesium, and potassium until 2 months past expected term, then a term infant formula. Term infants (n = 38; birth weight, 3318 +/- 401 gm) fed this term infant formula from birth were a reference group for comparison with study infants and with published values. Plasma mineral levels were analyzed by inductively coupled plasma atomic emission spectroscopy. RESULTS: Preterm infants fed a preterm infant formula after discharge from the hospital appeared to achieve normal plasma zinc concentrations by at least 2 months past term without adverse effects on mineral homeostasis.

Adolescent

Effect of different vitamin A intakes on very-low-birth-weight infants.

Formula-fed infants with birth weights < or = 1500 g (n = 61) were stratified by 250-g birth-weight ranges and randomly assigned to receive one of three preterm infant formulas (vitamin A contents of 820 IU, 1640 IU, or 2900 IU/MJ; 1 RE = 3.3 IU vitamin A activity) when subjects tolerated 0.314 MJ.kg-1.d-1. Experimental formula feedings were continued until infants weighed approximately 2 kg or until hospital discharge. Vitamin A status as indicated by serum retinol and retinol-binding protein (RBP) concentrations significantly decreased during experimental formula feeding at the lowest vitamin A intake. All subjects fed the formula providing the lowest vitamin A intake had hyporetinolemia (< 0.70 mumol/L, or < 20 micrograms/dL), which occurred less frequently (P < 0.05) with the intermediate (6 of 20) and the high (6 of 21) vitamin A intakes. Other outcome measures, including increases in weight, length, and head circumference, and ventilatory support and oxygen therapy, were not different among groups. After the end of the experimental formula-feeding period, all infants were fed standard infant formulas with a vitamin A content of 715 IU/MJ. In a subset of 19 of these infants, subsequent vitamin A status was monitored at ages 6-12 mo and was found to be comparable with that of older children and adults, regardless of the vitamin A content of the formula fed during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Case report: effect of pregnancy on idiopathic juvenile osteoporosis.

Adolescence and pregnancy are periods with increased calcium requirement. Therefore, patients with underlying bone disease are at risk for further bone demineralization during these periods. In this article, the authors report on the treatment during pregnancy of an adolescent with idiopathic juvenile osteoporosis that resulted in a favorable outcome of maternal and fetal skeleton.

Adolescent

Effect of three levels of vitamin D intake in preterm infants receiving high mineral-containing milk.

Very low-birth weight (VLBW) infants fed high-calcium and high-phosphorus (10.74 and 6.93 mmol/MJ; 180 and 90 mg/100 kcal, respectively) infant formulas were randomized to one of three levels of vitamin D intake to approximate 200, 400, and 800 IU/day. Sixty-two infants completed the study (24 to 29 days), with actual mean daily vitamin D intakes of 161, 361, and 766 IU, respectively. Outcomes were not different by group: gains in body weight, length and head circumference, serum calcium, magnesium, phosphorus, alkaline phosphatase, osteocalcin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and urine calcium:creatinine and magnesium:creatinine ratios. There were no radiographic fractures and/or rickets. A subset of 19 infants was followed between 173 and 380 days to determine descriptively if there was any delayed effect of earlier manipulation of vitamin D intake. They were fed standard infant formulas with a vitamin D content of 400 to 420 IU/L. No significant differences were present among the three groups, and data were combined. Serum 25-hydroxyvitamin D increased (p < 0.05), osteocalcin decreased (p < 0.05), and 1,25-dihydroxyvitamin D decreased (p = 0.06) at follow-up. Thus, for VLBZW infants fed high-calcium and high-phosphorus milk, an average daily vitamin D intake as low as 160 IU maintains normal and stable vitamin D status and normal physical growth, biochemical and hormonal indexes of bone mineral metabolism, and skeletal radiographs versus randomized infants receiving about 400 or 800 IU of vitamin D per day. On follow-up, vitamin D status remained normal for > or = 6 months while infants received < 400 IU of vitamin D per day.

Animals

Insulin-like growth factor (IGF)-I and IGF-binding protein 3 during the first year in term and preterm infants.

Plasma IGF-I and IGF-binding protein 3 (IGFBP-3) were determined by radioimmunoassay in term infants (n = 51) at 0, 2, 4, 6, and 12 mo and preterm infants (n = 51) at -3 (28.4 wk postconceptional age), -2, -1.5, -1, 0, 2, 4, 6, 9, and 12 mo from expected term. The effects of gestational age at birth (term or preterm) and study age were determined by repeated measures analysis of variance and Fisher's least squares difference. In preterm infants, IGF-I increased between -3 and 2 mo from 0.75 to 10.4 nM, decreased between 2 and 9 mo to 7.3 nM, and increased again between 9 and 12 mo to 10.1 nM (p < 0.0001), whereas IGFBP-3 increased relatively little from -3 to 0 mo (14.2 to 30.2 nM, p < 0.05) and plateaued from 2 to 12 mo (49.8 to 62.3 nM). At 0 mo, IGF-I and IGFBP-3 were the same in term and preterm infants, but preterm infants had higher IGF-I from 2 through 12 mo (p < 0.05), higher IGFBP-3 at 2 and 4 mo (p < 0.05), and lower IGFBP-3 at 12 mo (p < 0.05). IGF-I and IGFBP-3 were correlated at most ages. First year IGF-I and IGFBP-3 are influenced by study age and by gestational age, even after adjusting for early birth.

Carrier Proteins

Nutrient needs of the preterm infant.

Preterm infants exhibit special nutrient needs that differ substantially from other patient populations. Special characteristics include increased energy and protein requirements that must be addressed to prevent tissue catabolism and support growth. The immaturity of some organ systems may also complicate the administration of nutrition support. This article describes important characteristics of enteral and parenteral nutrition as it applies to the preterm infant.

Enteral Nutrition

Mineral nutrition and bone mineralization in full-term infants.

Bone mineralization is an intricate and tightly regulated process. Calcium, magnesium and phosphorus are the main minerals and play a principal role in skeletal mineralization. The following conclusions can be derived from different clinical studies. The large differences in Ca/P ratio between different formulas and between formulas and human milk suggest that most healthy full-term infants can adjust to a wide range of Ca/P ratio in their diet. The differences in serum levels of mineral and of mineral-regulating hormones are rarely clinically significant and most probably reflect continued compensatory mechanisms activated in response to dietary differences to maintain these levels within clinically normal ranges. Thus in most cases, these compensatory mechanisms are sufficient to reverse both short-term and long-term consequences and to prevent clinical disease. In the case of neonatal tetany, the compensatory mechanisms are overwhelmed, resulting in clinical signs and disease. Vitamin D is known to play an essential role in bone mineralization. Our studies have shown significant differences in vitamin D status in breast-fed infants with and without vitamin D supplementation and in infants fed various "humanized" formulas, whether cow milk-based or soy protein-based. The major variables affecting bone mineralization are Ca/P ratio and mineral-regulating hormones. However, factors such as season, geography (i.e. sun exposure), race and sex may have a significant long-term influence on bone mineralization and mineral metabolism. Some biological differences such as differences in serum vitamin D metabolite level may directly effect Ca/P absorption and retention and thus bone mineralization and growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density

Sequential serum aluminum and urine aluminum: creatinine ratio and tissue aluminum loading in infants with fractures/rickets.

Aluminum toxicity is associated with the development of bone disorders, including fractures, osteopenia, and osteomalacia. Fifty-one infants with a mean (+/- SEM) birth weight of 1007 +/- 34 g, gestational age of 28.5 +/- 0.3 weeks, and serial radiographic documentation at 3, 6, 9, and 12 months for the presence (n = 16) or absence (n = 35) of fractures and/or rickets were studied at the same intervals to determine the serial changes in serum aluminum concentrations and urine aluminum-creatinine ratios. Autopsy bone samples were used to determine the presence of tissue aluminum. Serum aluminum concentrations from 46 infants were stable and similar between groups, with mean values between 15 and 22 micrograms/L. Urine aluminum-creatinine (micrograms per milligram) ratios from 14 infants were higher in infants with fractures and/or rickets (0.26 +/- 0.06 vs 0.12 +/- 0.04) at onset, and rate of decrease in aluminum-creatinine ratio was faster in infants without fractures and/or rickets. All but three infants were tolerating complete enteral feeding at all sampling points. One infant who received aluminum-containing antacid had marked increase in serum aluminum to 83 micrograms/L while urine aluminum-creatinine ratio increased from 0.09 to a peak of 8.53. Vertebrae from three infants at autopsy (full enteral feeding was tolerated for 37 and 41 days in two infants, respectively) showed aluminum deposition in the zone of provisional calcification and along the newly formed trabecula.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

Mineral requirements of low-birth-weight infants.

The minerals calcium (Ca), magnesium (Mg), and phosphorus (P) are essential for tissue structure and function. Recent studies have resulted in a more rational approach to the management of mineral intake in preterm infants receiving parenteral nutrition (PN) and enteral nutrition (EN). For preterm infants requiring PN, the use of PN solutions with a Ca content of 1.25-1.5 mmol/dl (50-60 mg/dl), a P content of 1.29-1.45 mmol/dl (40-45 mg/dl), and an Mg content of 0.2-0.3 mmol/dl (5-7 mg/dl) is supported by studies of mineral homeostasis with serial chemical and calciotropic hormone measurements, standard balance studies, and improved radiographic indices of bone mineralization. For infants requiring EN, an intake of approximately 4 mmol (200 mg) of Ca, 3.2 mmol (100 mg) of P, and 0.33 mmol (8 mg) of Mg/kg/day based on an average retention rate of 64% for Ca, 71% for P, and 50% for Mg should be sufficient to meet the requirements of preterm infants in early infancy. This level of intake is supported by data from balance studies using standard and stable isotope techniques, changes in bone mineral content (BMC) measurements, and calciotropic hormone data. Based on the timing of development of fractures and rickets, changes in BMC, and skeletal growth data, the increased Ca and P intake should continue for at least 3 months after birth or until reaching a body weight of about 3.5 kg. In addition, nonnutritional factors may have the potential to increase mineral loss and disturb mineral homeostasis; chronic diuretic therapy increases mineral loss, and aluminum contamination of nutrients theoretically may compound any skeletal disorder. Thus, attention to the level of mineral intake and factors important in mineral loss and mineral metabolism should optimize mineral retention in small preterm infants.

Calcium

Sequential concentrations of copper and ceruloplasmin in serum from preterm infants with rickets and fractures.

Concentrations of copper (Cu) and ceruloplasmin in serum were measured serially in 49 preterm infants with mean (+/- SEM) birth weights of 979 +/- 33 g and gestational ages of 28.4 +/- 0.3 weeks at three, six, nine, and 12 months postpartum. Serial radiographic studies showed 17 infants with (group A) and 32 infants without (group B) rickets or fractures. Cu and ceruloplasmin concentrations in serum also were measured in 21 healthy term infants (group C) with birth weights 3668 +/- 98 g at three, six, and 12 months postpartum. Analyses of covariance of serial changes in these serum variables--taking into account such potential covariates as differences in gestational age, birth weight, initial weight and length, changes in weight and length during the study, the duration of parenteral nutrition, and increased enteral copper intake--showed both groups of preterm infants had significantly lower concentrations of Cu in serum up to age six months and ceruloplasmin up to age three months (P less than 0.001) when compared with term infants. By one year of age, Cu and ceruloplasmin concentrations in serum in all groups had increased significantly (P less than 0.001), into the adult range, and were not significantly different among groups. These data document a maturational lag in copper metabolism in small, preterm infants. Changes in concentrations of Cu and ceruloplasmin in serum were significantly correlated (r = 0.92, P less than 0.001) but were not significantly different between preterm infants with and without rickets or fractures at each age.

Aging

Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure.

One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure.

Bone Density

Lack of acute effect on lidocaine pharmacokinetics from parenteral nutrition.

We tested the hypothesis that amino acids in a parenteral nutrition (PN) solution would result in the decreased metabolism of a model compound, lidocaine. One bolus infusion of lidocaine HCl (1 mg/kg) was administered to seven healthy subjects in association with each of three nutrient regimens: (a) a standard PN solution, (b) 10% dextrose water (D10W), and (c) a meal (control) containing similar fluid volume and caloric, protein, and sodium content as the PN solution. Intravenous nutrients were infused consecutively in a random order at 1 L/12 h. Intravenous and control studies were performed 28 days apart. There was no significant difference in the means (+/- SEM) of total body clearance [7.70 +/- 0.70 (PN) versus 6.78 +/- 0.79 (D10W) versus 7.86 +/- 0.93 (control) ml/min kg], half-life [74.0 +/- 12.2 (PN) versus 89.6 +/- 4.35 (D10W) versus 79.2 +/- 7.22 (control) min], volume of distribution [0.82 +/- 0.15 (PN) versus 0.88 +/- 0.13 (D10W) versus 0.78 +/- 0.13 (control) L/kg], and the fraction of unbound lidocaine in the serum [0.34 +/- 0.025 (PN) versus 0.36 +/- 0.019 (D10W) versus 0.33 +/- 0.020 (control)] among the three nutrient regimens. The concentration-time course of the active metabolite, N-ethylglycyl-2,6-xylidide, did not differ significantly regardless of the nutritional regimen used. Our study indicates that amino acids used for PN do not have any acute effect on lidocaine pharmacokinetics in healthy subjects.

Adult

Effects of parenteral nutrition on hepatic elimination of lidocaine: a study using the isolated perfused rat liver.

The effects of acute and a short-term (7 days) parenteral nutrition (PN, consisting of 24.2% dextrose and 5.2% amino acids) on hepatic lidocaine elimination were studied using an isolated perfused rat liver preparation. In the acute study, lidocaine was coinfused with PN solution or normal saline at 0.123 ml/min for 80 min. There was no significant difference in hepatic lidocaine elimination between control and PN-treated groups (six per group). In the post-PN study, only lidocaine was infused for 80 min. Lidocaine hepatic clearance and extraction ratio were reduced by 29.8 and 31.1% (P less than .05), respectively, compared to what occurred in livers isolated from control animals with free access to standard laboratory rat-chow and water (six per group). Mass balance at steady state showed that recovery was higher for lidocaine (46.58 +/- 7.28% vs. 25.56 +/- 5.59%) and lower for N-(N,N-diethylglycyl)-2-hydroxymethyl-6-methylaniline (0.21 +/- 0.01% vs. 2.75 +/- 0.58%) in the PN group compared to chow-fed controls. Recoveries of other lidocaine metabolites: N-(N-ethylglycy)-2,6-xylidine, 3-hydroxylidocaine, 3-hydroxy-N-(N-ethylyglycyl)-2,6-xylidine and N-(N-ethylglycyl)-2-hydroxymethyl-6-methylaniline were similar in the PN- and chow-fed group. These findings suggest that acute PN infusion has no effect on lidocaine metabolism, and that the impaired hepatic lidocaine elimination after 7-days of PN occurs as a result of selective inhibition of hepatic enzyme activities such as those involved in aryl methyl hydroxylation and in other unidentified metabolic pathway(s).

Amino Acids