Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls.

To evaluate the changes in calcium and bone mineral metabolism associated with early pubertal development, we performed longitudinal measurements of calcium absorption, calcium kinetics, bone mineral content, and hormonal markers related to puberty in a multiethnic group of girls beginning when they were 7 or 8 yr old. Girls were Tanner stage 1 (breast) at the start of the study. They were placed on a 1200 mg/day dietary calcium intake and studied at approximately 6-month intervals until they reached Tanner stage 2 (breast). Results at that time point (PUB) were compared to values obtained approximately 1 yr earlier (LatePRE) and those 1 yr before that (EarlyPRE). We found an increase in calcium absorption comparing PUB to LatePRE (n = 34; 36.6 +/- 8.7% vs. 30.7 +/- 9.9%; P = 0.002). Using whole body, dual energy, x-ray absorptiometry scanning, we found an increase in calcium gain during the LatePRE to PUB period compared with that during the EarlyPRE to LatePRE period (135 +/- 53 vs. 110 +/- 45 mg/day; P = 0.04). Calcium kinetic studies showed a significant increase in the bone calcium deposition rate (Vo+) during the PUB compared to the LatePRE period. Hormonal and biochemical markers of bone development were also significantly increased at PUB compared to LatePRE. Hormonal activity, as evidenced by the unstimulated LH level, was significantly correlated with calcium gain between the LatePRE and PUB studies and the bone calcium deposition rate in the PUB study. These data demonstrate, using multiple independent methods, an increase in calcium utilization associated with the earliest physical signs of puberty.

Ethnic differences in androgens, IGF-I and body fat in healthy prepubertal girls.

OBJECTIVE: To examine ethnic differences in adrenal androgen production, IGF-I, and IGFBP-1 and -3 in relation to bone age, insulin, and body composition in healthy prepubertal girls. METHODS: Serum levels of DHEA-S, androstenedione, IGF-I, and IGFBP-1 and -3 were examined in relation to bone age, insulin, and body composition (determined by dual-energy X-ray absorptiometry) in 47 (19 Caucasian, 9 African-American, 19 Mexican-American) healthy prepubertal girls aged 7.5-9.0 years. RESULTS: Age, weight, height, bone age, androstenedione, insulin, glucose:insulin ratios, and IGFBP-3 levels were not statistically different among groups. Mexican-American girls had higher % body fat than African-Americans or Caucasians (P < 0.001). DHEA-S levels in African-Americans were twofold higher than in Caucasians (P = 0.024), although their % body fat was not significantly different (16.1% and 19.4%, respectively; P = 0.138). DHEA-S levels in Mexican-American girls were intermediate. Bone age and weight were significant covariates for DHEA-S levels. Plasma IGF-I levels were also higher in African-American than in Caucasian or Mexican-American girls (P = 0.009). Covariance analysis showed that IGF-I levels were influenced mainly by ethnicity (P = 0.009) and were independent of bone age. Despite similar insulin levels among groups, IGFBP-1 levels were higher in Caucasians than in Mexican-Americans or African-Americans (P < 0.001). CONCLUSIONS: In healthy prepubertal girls, DHEA-S concentrations are higher in African-Americans than in Caucasians or Mexican-Americans, even before any clinical evidence of adrenarche. Furthermore, IGF-I concentrations are higher in African-American girls than in Caucasian or Mexican-American girls which may contribute to the higher DHEA-S levels observed. Conversely, higher DHEA-S and IGF-I levels in African-American girls may be indicative of an influence not only of gonadal but also of adrenal androgens on the GH/IGF-I axis.

Identification of thyroxine-binding globulin-San Diego in a family from Houston and its characterization by in vitro expression using Xenopus oocytes.

T4-binding globulin (TBG) is a liver glycoprotein that transports iodothyronines in serum. Several TBG variants with reduced T4 binding affinity have been described, all of which are also characterized by reduced serum TBG concentrations and reduced heat stability. Their loss of binding thus appears to be due to a general defect of the molecule. We now report the occurrence of a variant TBG, detected in a family from Houston, TX, with half the normal T4 binding affinity and heat stability but normal serum concentration and isoelectric focussing pattern. The propositus was identified by reduced total T4 and T3 serum levels. All family members were euthyroid, and inheritance followed an X-linked pattern. Sequence analysis of the TBG gene of the propositus and his heterozygous mother revealed two amino acid substitutions: serine 23 with threonine (S23T), and the known polymorphism leucine 283 with phenylalanine (L283F). These substitutions are identical to those of TBG-San Diego (TBG-SD), a variant with similar properties except for a reduced serum concentration. Expression of recombinant TBG-SD/H with the S23T substitution in Xenopus oocytes reproduced the binding defect and heat lability. The amount of TBG-SD/H synthesized and secreted by the oocytes was not different from that of normal TBG. The difference in serum TBG concentrations in affected members of the San Diego and Houston families thus does not appear to be due to an error in the measurement of TBG, but may be related to differences in the rates of degradation.

Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children.

The vitamin D receptor (VDR) gene has been implicated as one of the major genetic components of osteoporosis. We evaluated the relationship between markers of mineral status and restriction fragment length polymorphisms of the VDR gene in 72 healthy children age 7-12 years. Using stable isotope techniques and dual-energy X-ray absorptiometry, we measured dietary calcium absorption, bone calcium deposition rates, and total body bone mineral density (BMD). The Fok1 polymorphism at the VDR translation initiation site was significantly associated with BMD (p = 0.02) and calcium absorption (p = 0.04). Children who were FF homozygotes had a mean calcium absorption that was 41.5% greater than those who were ff homozygotes and 17% greater absorption than Ff heterozygotes. BMD was 8.2% greater in the FF genotype than the ff genotype and 4.8% higher than the Ff genotype. These results suggest a substantial relationship between the VDR gene and bone metabolism at one or more levels, including dietary absorption of calcium and BMD in growing children.

Calcium absorption and kinetics are similar in 7- and 8-year-old Mexican-American and Caucasian girls despite hormonal differences.

To assess the possibility of ethnic differences in mineral metabolism in prepubertal children, we compared measures of calcium metabolism in 7- and 8-y-old Mexican-American (MA) and non-Hispanic Caucasian (CAU) girls (n = 38) living in southeastern Texas. We found similar fractional calcium absorption, urinary calcium excretion, calcium kinetic values and total-body bone mineral content in the MA and CAU girls. In contrast, parathyroid hormone (PTH) concentrations were greater in MA girls (4.01 +/- 0.47 vs. 1. 96 +/- 0.50 pmol/L, P = 0.005) than in CAU girls. Serum 25-hydroxyvitamin D concentrations were lower in MA girls (68.9 +/- 7.7 vs. 109.4 +/- 8.4 nmol/L, P = 0.001) than in CAU girls, but 1, 25-dihydroxyvitamin D concentrations did not differ between groups. Seasonal variability was seen for 25-hydroxyvitamin D concentrations in girls of both ethnic groups, but values in all of the girls were >30 nmol/L (12 ng/mL). We conclude the following: 1) greater PTH levels in MA girls than CAU girls are present without evidence of vitamin D deficiency; and 2) differences in 25-hydroxyvitamin D and PTH concentrations between MA and CAU girls do not have a large effect on calcium absorption, excretion or bone calcium kinetics. These data do not provide evidence for adjusting dietary recommendations for mineral or vitamin D intake by MA girls.

Continuous venovenous hemofiltration: a cost-effective therapy for the pediatric patient.

The authors were surprised to discover that at Riley Hospital for Children the cost of continuous venovenous hemofiltration (CVVH) constitutes a small fraction of the total admission costs, even when it is performed for a large portion of inpatient stays. A reasonable treatment that gives critically ill children reasonable chances of surviving at reasonable costs, must be considered cost-effective. CVVH currently offers some pediatric patients an additional chance at survival without an extraordinary increase in total hospital bills. Further research regarding patient selection, timing of initiation of therapy, and improving outcomes is recommended.

Gastrointestinal symptoms and diabetes mellitus in children and adolescents.

Because it may be difficult to evaluate gastrointestinal diseases in children with insulin-dependent diabetes mellitus (IDDM), this report highlights several clinical features unique to diabetes and emphasizes the relationship between gastrointestinal pathology and glycemic control. Two children with IDDM are described whose hyperglycemia, ketosis, and abdominal pain were the presenting features of H. pylori-positive duodenal ulcer disease and acute appendicitis, respectively. A third nondiabetic child developed persistent postprandial hyperglycemia as the initial manifestation of dumping syndrome. These patients illustrate the relationship between glycemic control and gastrointestinal pathology in children with diabetes and the effects of gastrointestinal dysfunction on glucose regulation in nondiabetic children. In children with IDDM, gastrointestinal pathology can be confused with ketoacidosis and complicate diabetes control and management. Early recognition and treatment of the underlying gastrointestinal disease often improves glycemic control. Furthermore, severe gastrointestinal dysfunction in nondiabetic children may deleteriously influence glycemic regulation and may be confused with childhood diabetes.

Mortality prediction and interval until death in near-term and term neonates with respiratory failure.

Mortality risk indicators may be useful adjuncts to clinical judgment in considering the use of extraordinary and relatively high-risk treatments such as high-frequency ventilation, extracorporeal membrane oxygenation, and nitric oxide therapy. We retrospectively evaluated the reliability of published indications of high mortality, developed additional high-risk indicators, and determined the interval between the time when high-risk indicators were met and when death occurred in near-term and term neonates with respiratory failure. Patients were included in the analysis if they met the following criteria: > or = 35 weeks gestation, > or = 2 kg birth weight, < or = 7 days of age, and receiving a fraction of inspired oxygen of > or = 0.8 and mechanical ventilation. Patients were excluded if they had congenital heart disease, intracranial hemorrhage, untreatable bleeding diathesis, or lethal congenital anomaly. Fifteen patients in the 1980 to 1981 group and 41 patients in the 1985 to 1987 group met these criteria. We observed 100% mortality in our 1980 to 1981 patients who met previously published criteria predictive for > or = 80% mortality in near-term and term neonates with respiratory failure; however, mortality risk was 60% to 80% in the 1985 to 1987 group.(ABSTRACT TRUNCATED AT 250 WORDS)