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OBJECTIVE: Because the causes of nutritional rickets in tropical countries are poorly understood, we conducted a case-control study to determine factors associated with rickets in Nigerian children. STUDY DESIGN: We compared 123 Nigerian children who had rickets with matched control subjects. Dietary, demographic, anthropometric, and biochemical data were collected to assess factors related to calcium and vitamin D status, which might predispose children to rickets. RESULTS: Mean (+/- SD) daily dietary calcium intake was low in both children with rickets and control children (217 +/- 88 mg and 214 +/- 77 mg, respectively; P =.64). Children with rickets had a greater proportion of first-degree relatives with a history of rickets (14.6% vs 3.1%; P <.001), a shorter mean duration of breast-feeding (16.0 vs 17.3 months; P =.041), and a delayed age of walking (14 vs 12 months; P <.001). Among children with rickets, biochemical features suggestive of calcium deficiency included hypocalcemia, extremely low calcium excretion, and elevated 1, 25-dihydroxyvitamin D and parathyroid hormone values. Median 25-hydroxyvitamin D concentrations were 32 and 50 nmol/L (13 and 20 ng/mL) in children with rickets and control children, respectively (P <.0001). Only 46 subjects with rickets (37%) had 25-hydroxyvitamin D values <30 nmol/L (12 ng/mL). CONCLUSIONS: Vitamin D deficiency appears unlikely to be the primary etiologic factor of rickets in African children. Moreover, low dietary calcium intake alone does not account for rickets. Insufficient dietary calcium probably interacts with genetic, hormonal, and other nutritional factors to cause rickets in susceptible children.

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OBJECTIVES: To determine whether osteopenia is evident in prepubertal children with cystic fibrosis (CF) and, if so, whether it is caused by a deficiency in bone formation or increased bone resorption. STUDY DESIGN: With the use of a prospective case control study design, we investigated 11 prepubertal children with CF between the ages of 8 and 12 years old and a non-CF control group matched by weight and sex. Bone density at the radius, ulnar, trochanter, femoral neck, and lumbar spine, biochemical markers of bone metabolism, calcium, vitamin D metabolites, and intact parathyroid hormone were measured in all subjects. Comparisons between the 2 groups were performed with Wilcoxon matched pairs and Fisher exact tests. RESULTS: Intake of total calories, calcium, phosphorus, and vitamin D was significantly greater in the CF group than in the control group. Serum 25(OH)vitamin D levels were significantly lower in the CF group: median 22 ng/mL for the CF group and 39 ng/mL for the control group (P =.02). 1,25(OH)(2) vitamin D levels were borderline or low in 7 subjects in the CF group and 2 members of the control group (P =.08, Fisher exact test). Intact parathyroid hormone levels were higher than the upper limit of normal in 4 subjects of the CF group and 1 member of the control group. Despite these biochemical abnormalities, we found no evidence of bone mineral deficiency in the CF group. CONCLUSIONS: Prepubertal children with CF do not have bone mineral deficit compared with a weight- and sex-matched control group; however, their lower vitamin D levels may portend problems with bone mineralization during adolescence and adulthood.

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LCP supplementation of premature infant formula has been shown to produce plasma and erythrocyte lipid profiles similar to human milk (HM)-fed preterm infants. Previous studies reported decreased growth with LCP supplemented formula. This prospective, double-blind, randomised, controlled, parallel trial compared safety, growth and phospholipid fatty acid (PFA) levels in preterm infants fed preterms formula with (L+) or without (Lo) LCP. The study consisted of Phase I: enrolment to 40 weeks (wk) postconceptual age (PCA); and Phase II: 40 to 48 wk PCA. Infants (birth weight 750-2000 g, 0-28 days of age) were fed L+ or L preterm formula, 24 Kcal/oz during Phase I, and 20 Kcal/oz during Phase II. A control group was exclusively HM-fed preterms who, if weaned at the end of Phase I, received L. HM and formula intake were unrestricted. Weight (wt), length (Lt), head circumference (OFC) and upper mid-arm circumference (MAC), and phospholipid profiles were measured at 40 and 48 wk PCA. Adverse events were monitored. 183/288 infants completed Phase II. There were no difference in growth rates between formula groups. At 48 wk PCA, mean PFA levels in infants fed L+ were similar to HM-fed and were significantly higher than the L fed group. Adverse events were similar between the 2 formula groups. The number of infants who were discontinued because of an adverse event was similar among all groups. In conclusion the LCP preterm infant formula is safe, support normal growth and maintains phospholipid profiles similar to HM-fed infants.(AU)

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A strategy based on the use of PCR with one degenerate oligonucleotide deduced from conserved sequences and lambda gt10 primers was used to isolate homeobox containing sequences from sunflower stem and root cDNA libraries. Six different partial cDNAs coding for the first 48 amino acids of homeodomains and amino terminal sequences were analyzed and found to be members of the HD-Zip superfamily, which contain a homeobox linked to a leucine zipper coding region. A full-length cDNA clone, Hahb-10, was isolated and characterized. The leucine zipper portions of Hahb-10 and of the previously reported Hahb-1 have been utilized to construct fusions with the N-terminal domain of the lambda repressor. These fusions were tested for their ability to bind to lambda promoters in vivo. The expression of a protein containing an active dimerization domain, but not capable of DNA binding, exerts a dominant negative effect on the ability of repressor-zipper fusions to bind to its target DNA. From these experiments, it was concluded that Hahb-1 and -10, when co-expressed, form preferentially homodimers. Exchange of conserved threonines and leucines at positions a1 and d1 of both zippers reduces dimerization efficiency and allows the formation of heterodimers, suggesting that these residues are, among others, determinants of the specificity of interaction, most likely through changes in hydrophobic packing interactions at the dimer interface. The results imply that a great number of interacting molecular entities compose this protein superfamily which is presumably involved in regulating plant developmental responses.

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A study was undertaken to identify the common micro-organisms occuring in induced sputum specimens from HIV-infected/non-infected individuals with pulmonary manifestations in Trinidad. Only 13 percent of HIV seropositive patients with pneumonia were found to be positive for P. carinii. This low yield may have been due to low prevalence of the P. carinii in Trinidad or to prior antibiotic therapy. Active mycobacterial infection was demonstrated in only 13 percent HIV seropositive patients with pneumonia, though 43 percent HIV patients had a clinical diagnosis of tuberculosis. This may have been due to the low sensitivity of the acid-fast technique. The most common microbial pathogen is identified in HIV patients with pneumonia was Candida sp. Followed by gram negative bacteria. A listing is made of the various organisms occuring singly or mixed in HIV seropositive and HIV seronegative patients (AU)

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OBJECTIVE: A 4-week pilot study was done with 26 preterm infants to evaluate whether a physical activity program would result in greater bone mineralization. DESIGN: Subjects were matched by birth weight, gender, and gestational age, and randomly assigned to the physical activity program (group EX; n = 13) or to the control group (group C; n = 13). Physical activity consisted of range of motion with passive resistance to all extremities for 5 to 10 minutes daily. Baseline and 4-week values were determined for both bone mineral analyses and serum levels of calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25-hydroxy-vitamin D. RESULTS: Despite similar nutrient intake at advised levels for preterm infants, EX infants gained more weight than control subjects (17.8 vs 13.4 gm/kg body weight per day; p = 0.01). A difference in radial bone mass and density change as determined by single-beam photon absorptiometry (+/- 2% error) was found between groups (p = 0.006 by analysis of covariance). Changes in bone width and in bone mineral content and density were enhanced by physical activity. Group EX infants had 12%, 18%, and 34% gains in bone width and in bone mineral density and content, respectively; group C infants had only a 2% gain in bone width and 11% and 14% losses from baseline in bone mineral content and density, respectively, during the 4-week study. Serum biochemical values were similar in the groups except for lower alkaline phosphatase levels in group EX. There was a negative association between bone mineral content and parathyroid hormone values: r = -0.83, p = 0.01. CONCLUSIONS: A physical activity program may increase the effects of adequate nutrition in healthy preterm very low birth weight infants by promoting weight gain and bone mass and by decreasing the risk of osteopenia.

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OBJECTIVE: To study the effect of calcium supplementation with dairy products on the bone and body composition of pubertal girls. DESIGN: Randomized control study with 12-month follow-up. SETTING: General community. SUBJECTS: Forty-eight white girls whose mean age was 11 years and sexual development at Tanner stage 2. INTERVENTION: One group's diet was supplemented with dairy products to the recommended dietary allowance of 1200 mg calcium daily. The other group ate their usual diet. MAIN OUTCOME MEASURES: Bone mineral content and density were measured at the radius, femoral neck, lumbar spine, and total body bone mineral by single-photon and dual-energy x-ray absorptiometry at the start of the study and after 3, 6, 9, and 12 months. Body composition (lean body mass and body fat) was measured by dual-energy x-ray absorptiometry at the same intervals. Serum calcium, phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, alkaline phosphatase, magnesium, and albumin concentrations were determined at the start and end of the study. The urinary calcium/creatinine ratio and hydroxyproline concentration were also determined. RESULTS: The dairy group had higher intakes of calcium, phosphate, vitamin D, and protein than control subjects. The dairy group had significantly greater increases during the 1-year study in bone mineral density at the lumbar spine bones (22.8% +/- 6.9% vs 12.9% +/- 8.3%) and in total body bone mineral (14.2% +/- 7.0% vs 7.6% +/- 6.0%) than control subjects. Dietary calcium, phosphate, vitamin D, and protein intakes were associated with the lumbar bone density and total body bone calcium. There were no differences in serum or urinary biochemical values between the two groups at the start or end of the study. CONCLUSIONS: Young girls whose dietary calcium intake was provided primarily by dairy products at or above the recommended dietary allowances had an increased rate of bone mineralization. Increased intake of dairy foods did not increase overall total or saturated fat intake and was not associated with excessive weight gain or increased body fat.

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The objective of this study was to determine whether the growth and bone mineral status of discharged preterm infants fed human milk differed from those of infants fed one of three different formulas varying in calcium content (545 mg/L, 660 mg/L, or 1290 mg/L). A randomized, blinded study was conducted for 16 weeks after discharge in 16 human milk-fed and 43 formula-fed infants. All formula-fed infants received one of the three study formulas from discharge to 8 weeks afterward, and the standard formula, which contained 545 mg/L calcium, from 8 to 16 weeks. The human milk-fed infants gained weight more slowly than the formula-fed infants. The human milk-fed infants also had lower gains in length and higher serum alkaline phosphatase values than the formula-fed infants. The infants who received the formula containing the highest calcium concentration (1290 mg/L) had greater bone mineral density during the first 8 weeks of the study. We conclude that preterm infants recently discharged from the hospital may benefit from higher calcium intake than is provided by either human milk or standard term formula.

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Infants fed a soy formula supplemented with selenite had plasma and erythrocyte selenium values lower than those of infants fed human milk. However, plasma and erythrocyte glutathione peroxidase activities were normal, indicating that the physiologic requirement for selenium was being met.

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The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.

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We describe a newborn with congenital cystic eye, contralateral persistent hyperplastic primary vitreous, and cerebrocutaneous abnormalities. The cerebrocutaneous abnormalities consisted of agenesis of the corpus callosum, midbrain deformity, malformed sphenoid bone, right upper eyelid coloboma, and a left periocular hamartoma. The results of karyotype analysis of the patient and his parents were normal. The association of congenital cystic eye with contralateral persistent hyperplastic primary vitreous has not been previously reported, to our knowledge. Although no unifying diagnosis exists for the collection of anomalies demonstrated in this patient, the term cranial ectodermopathy broadly classifies most of the defects.

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We studied postnatal bone mineralization, as measured by photon absorptiometry, in 36 preterm infants (birth weight less than 1600 gm) who were fed (1) a commercial premature formula containing 117 mg calcium and 58.8 mg phosphorus per 100 kcal, (2) the same formula containing a higher concentration of phosphorus (82 mg/100 kcal), (3) the same formula with higher concentrations of calcium (140 mg/100 kcal) and phosphorus (82 mg/100 kcal), or (4) their mother's milk. Serum calcium, phosphorus, protein, albumin, bicarbonate, 25-hydroxyvitamin D, and alkaline phosphatase levels were measured at the start of the study and every 2 weeks until the infants achieved a weight of 1900 gm. Birth weights and gestational ages were similar in all four groups. The human milk group had lower serum phosphate and bone mineral values than those in the three formula groups. Bone mineral content was similar in the three formula groups. However, only the formulas of the first and third groups allowed approximation of the intrauterine bone mineralization curve. Bone mineral content in infants fed human milk was below the intrauterine rate.

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To determine the calcium and bone mineral status of lactating adolescents, we compared 12 lactating adolescents with 11 nonlactating adolescents, 11 lactating adults, and 11 nulliparous adolescent control subjects. At two and 16 weeks, there were no differences in maternal serum concentrations of calcium, phosphorus, alkaline phosphatase, or calcidiol (25-hydroxyvitamin D). The bone mineral content at two weeks among the four groups was not different, but at 16 weeks the lactating adolescents' bone mineral content was lower than that in the other groups. The lactating adolescents' bone mineral content was decreased between two and 16 weeks (1.049 +/- 0.088 vs 0.887 +/- 0.054 gm/cm; P less than 0.02). Dietary intakes were similar among the groups for calories, protein, vitamin D, calcium, and phosphorus. However, only three of ten lactating adolescents met the recommended dietary allowance for calcium or phosphorus (1,600 mg/day), whereas eight of ten nonlactating adolescents, six of seven lactating adults, and seven of ten adolescents control subjects met the recommended dietary allowance for calcium or phosphorus (P less than 0.05). Our data suggest that during 16 weeks of lactation, the adolescent mother may be at risk for bone demineralization because of low dietary intakes of calcium or phosphorus.

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To determine if human milk provides sufficient nutrients for adequate bone mineralization in healthy term infants, 76 term Caucasian infants were evaluated at 2 and 16 weeks of age. The infants and their mothers were divided according to the infant's diet into three groups: human milk alone, human milk with supplemental vitamin D, and Similac. At 2 and 16 weeks of age, bone mineral content was measured by photon absorptiometry and blood was drawn for measurement of serum calcium, phosphate, alkaline phosphatase, and 25-OH vitamin D. At both 2 and 16 weeks of age, BMC was similar among all three feeding groups. At 16 weeks of age there was no difference in serum total Ca, ionized Ca, P, or alkaline phosphatase values. At 16 weeks of age the serum 25-OH D concentration was lower in the infants fed human milk alone (P less than 0.05), but was within the normal adult range. Maternal BMC and serum 25-OH D values are similar among the three groups. No seasonal effect on BMC was observed. Our data suggest that during the first 16 weeks of life, routine vitamin D supplementation for breast-fed term Caucasian infants may not be necessary.

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The premature infant has a limited capacity for fatty acid oxidation. This study shows that solutions commonly used for intravenous feedings in the newborn infant contain no carnitine. Infants maintained on this solution have significantly lower total, free, and acylcarnitine levels as compared to when they are fed orally with expressed human milk or a proprietary formula, which is known to contain carnitine. The exogenous supply of carnitine to the premature infant may have a significant influence on the ability to stimulate optimal fatty acid oxidation.

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Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.

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The ketogenic potential of Intralipid was studied in two groups of infants: 12 were SGA and 15 AGA; all were clinically stable and less than 48 hours of age. During four-hour Intralipid tolerance tests, the SGA infants achieved significantly higher plasma TG and FFA levels. Both groups of infants significantly increased the concentration of ketone bodies; however, there was no difference in the levels achieved. In view of the slower clearance rate of TG and the higher levels of FFA in SGA infants, it is speculated that in addition to a possible defective lipoprotein lipase system and a decrease in number and size of the adipose cells, beta-oxidation of FFA to ketones may be occurring at a slower rate. The generation of high levels of ketones during Intralipid infusion period in both groups of infants indicates that SGA infants can handle ketone bodies as readily as AGA infants.

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Ten newborn infants were given gentamicin intramuscularly. Over a postinjection interval of 12 hours, no significant change occurred in the total binding capacity of serum albumin for bilirubin or in concentrations of serum bilirubin levels. There was no correlation between concentrations of serum gentamicin and the total binding capacity or serum bilirubin. This study provides in vivo data that supports recent in vitro experiments showing that gentamicin does not alter bilirubin-albumin binding.

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To assess the rationale of albumin priming prior to exchange transfusions, 42 hyperbilirubinemic infants who required exchange transfusions were randomly assigned to one of two groups. Group I consisted of 15 infants who were given intravenously 1 gm/kg of salt-poor human serum albumin one hour before the exchanges. Group II, which consisted of 27 infants, received simple exchanges. No statistical differences were found in variations in reserve albumin-binding capacity, bilirubin, albumin, or red cell bilirubin at pre and one-hour post albumin infusion in the primed infants. The amount of bilirubin removed per kilogram is directly correlated to plasma bilirubin concentration (r=0.87). No significant difference in efficiency on bilirubin removal was seen between the two groups. Beneficial effects of albumin therapy was apparent only in those infants with low RABC as determined by the sephadex gel filtration technique.

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