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Biomedical subjects

A L Yergey

Publications and source records attributed to A L Yergey.

At least 55 records · Page 3Linked to original sources

Hypercalciuria in premature infants receiving high mineral-containing diets.

We evaluated urinary calcium excretion in 21 premature infants fed either a formula containing high concentrations of calcium (Ca) and phosphorus (P) or human milk fortified with a commercially available human milk fortifier. Dual-tracer stable-isotope Ca absorption studies were performed on all infants. Urinary Ca excretion was not significantly related to Ca or P intake or true Ca absorption. The recovery of the orally administered tracer in the urine was used to evaluate the source of calciuria in study subjects. In almost all subjects, tissue-derived (Vbu), rather than diet-derived (Vou), Ca was the principal source of urinary Ca. Hypercalciuric subjects demonstrated greater Vbu and Vou than nonhypercalciuric subjects. Our data demonstrate that moderate hypercalciuria is common in premature infants whose diets are high in mineral content and that hypercalciuria is not related to inadequate mineral intake or Ca absorption but is related, instead, to losses of both tissue and dietary Ca.

Birth Weight↗

Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.

We investigated the effects of 4-6-wk administration of testosterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age +/- SE = 12.9 +/- 0.6 yr). At baseline, subjects received a 4-h infusion of L-[1-13C]leucine and L-[2-15N]glutamine, and were given 42Ca intravenously, and 44Ca PO. Testosterone enanthate (approximately 3 mg/kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection. After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention (Vbal) also increased (Va 13.3 +/- 2.3 vs 21.5 +/- 2.3; mg.kg-1.d-1, Vbal 8.0 +/- 2.1 vs 16.6 +/- 2.5, mg.kg-1.d-1, P < .05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6 +/- 5.9%, P = 0.036. Leucine oxidation decreased by 48.6 +/- 8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4 +/- 7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%). In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors.

Calcium↗

Compartmental analysis of calcium metabolism in very-low-birth-weight infants.

The calcium metabolism of 13 very-low-birth-weight infants fed a high-calcium diet was evaluated by means of stable isotope kinetic and balance studies. The studies used orally and i.v. administered stable isotopes, and the kinetic data were evaluated with the aid of a sequential, three-compartment model. The infants (postmenstrual age 33 +/- 1 wk, weight 1.34 +/- 0.03 kg) had higher bone calcium deposition rates (160 +/- 7 mg.kg-1.d-1 or 4.00 +/- 0.18 mmol.kg-1.d-1) than those previously reported for either older children or adults. Furthermore, when analyzed as a function of net calcium absorption, bone calcium deposition rates increased markedly and significantly as net calcium absorption increased (r = 0.70, p < 0.01), whereas in older individuals, bone calcium deposition is a relatively invariant function of absorption. A relatively smaller response of bone calcium removal to calcium absorption was found for the very-low-birth-weight infants in this study (r = -0.39, p = 0.18), whereas in adults, bone calcium removal constitutes the major regulatory response. It is suggested that the calcium kinetic results in the very-low-birth-weight infants reflect the high rate of bone growth typical of the third trimester of gestation.

Adult↗

Relationship between balance and dual tracer isotopic measurements of calcium absorption and excretion.

Calcium (Ca) absorption was measured by the balance method and the dual tracer isotopic method in 462 studies of adult women. Results for both fractional absorption and net Ca balance were similar using the 2 methods. Slightly higher values (mean difference, 0.031 +/- 0.092) were found for fractional absorption measured by the balance method than by the isotopic method. No differences in fractional absorption between the methods were seen at a fractional absorption less than 25%. Variability in the data was greater from the balance than the isotopic method. Endogenous fecal Ca excretion was directly related to Ca intake, with an estimated value of 70-80 mg/day for a Ca intake less than 200 mg/day. These findings support the usefulness and accuracy of isotope-based measures of mineral absorption. No evidence is found from these or previous data to suggest that the process of isotopic equilibration falsely increases estimates of absorption or endogenous excretion in tracer studies. Isotopic techniques allow studies of calcium absorption in diverse populations and evaluation of unique aspects of mineral metabolism not accessible through other techniques.

Absorption↗

Pathophysiology of hypocalciuria in preeclampsia: measurement of intestinal calcium absorption.

OBJECTIVE: To analyze calcium absorption using stable isotopes in patients with preeclampsia and in normotensive controls. METHODS: Fifteen pregnant subjects were studied: eight with preeclampsia (hypertension and proteinuria) and seven normotensive controls. All patients were ingesting their normal diet. The subjects received two stable calcium isotopic tracers. An oral tracer (44Ca, 0.0124 mmol/kg) was given with milk, while an intravenous tracer (42Ca, 0.00249 mmol/kg) was infused over 7-10 minutes. Calcium concentration was determined by atomic absorption spectrophotometry, and isotope ratios by thermal ionization mass spectrometry from pooled 24-hour urine samples. RESULTS: No difference was noted in fractional intestinal absorption between preeclamptic subjects (0.282 +/- 0.051) and normotensive controls (0.306 +/- 0.079) (P = .49). However, the fraction of dietary calcium appearing in the urine differed significantly (0.06 for preeclamptic subjects and 0.087 for normotensive controls; P = .008). CONCLUSIONS: Despite the indirect evidence of others, calcium absorption does not appear to be impaired in patients with preeclampsia. The retention site of the unexcreted calcium is unidentified.

Adult↗

Demonstration of a difference in urinary calcium, not calcium absorption, in black and white adolescents.

Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck is greater in black than in white children. Studies were performed to determine whether differences in intestinal absorption of calcium or urinary calcium or both account for an assumed more positive calcium balance and greater bone mass in black children. Normal black and white boys and girls were admitted to a metabolic ward and given a constant daily diet containing 1000 mg calcium, 60% as calcium carbonate, for 2 1/2 days (study I) or 3 1/2 days (study II). Fasting blood and 24 h urine collections were obtained, and in study II, unidirectional fractional absorption of calcium (alpha) was determined with stable isotopes of calcium. It was found that (1) serum 25-hydroxyvitamin D (25-OHD) and urinary calcium were lower and serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was higher in black than in white children, and (2) alpha was higher in boys than in girls with no racial difference, and (3) there were significant positive correlations between alpha and urinary calcium in the blacks and in the black and white children together. It is concluded that (1) alpha is higher in boys than in girls and (2) a lower urinary calcium, not increased intestinal absorption of calcium, is the means for a more positive calcium balance in blacks that accounts for the racial difference in BMD.

Absorption↗

Mineral balance and bone turnover in adolescents with anorexia nervosa.

We evaluated seven female adolescents with anorexia nervosa to determine whether calcium metabolism was affected by their disorder. We measured calcium absorption, urinary calcium excretion, and calcium kinetics, using a dual-tracer, stable-isotope technique during the first weeks of an inpatient nutritional rehabilitation program. Results were compared with those from a control group of seven healthy adolescent girls of similar ages. The percentage of absorption of calcium was lower in subjects with anorexia nervosa than in control subjects (16.2% +/- 6.3% vs 24.6% +/- 7.2%; p < 0.05). Urinary calcium excretion was greater in subjects with anorexia nervosa than in control subjects (6.4 +/- 2.5 vs 1.6 +/- 0.7 mg.kg-1 x day-1; p < 0.01) and was associated with bone resorption rather than calcium hyper-absorption. Calcium kinetic studies demonstrated a decreased rate of bone formation and an increased rate of bone resorption. These results suggest marked abnormalities in mineral metabolism in patients with anorexia nervosa. From these results, we hypothesize that improvement in bone mineralization during recovery from anorexia nervosa will require resolution of hormonal abnormalities, including hypercortisolism, in addition to increased calcium intake.

Absorption↗

Measurement of true absorption, endogenous fecal excretion, urinary excretion, and retention of calcium in term infants by using a dual-tracer, stable-isotope method.

A dual-tracer, stable-isotope method was used to measure the percentage of true calcium absorption (alpha), true calcium absorption rate (Va), endogenous fecal calcium excretion rate (Vf), urinary calcium excretion rate (Vu), and calcium retention rate (Vr). Twenty-seven infants with a mean gestation of 30.6 +/- 1.7 weeks and a mean birth weight of 1.4 +/- 0.21 kg were studied at 2 or 3 weeks of age, or both, during feedings of human milk (HM), fortified human milk (HMF), and commercially available formula (20 or 24 calories per ounce) for premature infants (EPF-20/780 and EPF-24/940) (part 1 of our study). Of 13 additional infants with a mean (+/- SD) birth weight of 1.26 +/- 0.25 kg and gestation of 29.6 +/- 2.5 weeks, 11 completed a crossover-design study at 2 and 3 weeks of age, receiving two identical formulas containing calcium, 940 mg/L, and phosphorus, 470 mg/L (EPF-24/940 formula) or calcium 1340 mg/L, and phosphorus, 680 mg/L (EPF-24/1340 formula) (part 2 of our study). The alpha value was higher in infants receiving HM (76.4 +/- 15.1%) or HMF (68.0 +/- 7.8%) than in those receiving EPF-20/750 formula (54.1% +/- 5.6%) or in previously reported infants fed standard formula (47.1% +/- 11.5%); those given EPF-24/940 formula had intermediate values (63.9% +/- 13.9%, part 1; 56.1% +/- 16.5%, part 2). No significant differences existed among groups for either Vu or Vf per kilogram. In the crossover study (part 2), no significant differences were seen between formulas for alpha and for Va, Vf, or Vr per kilogram. However, Vu per kilogram was significantly decreased in infants receiving the higher mineral formula (EPF-24/940: 3.6 +/- 2.3; EPF-24/1340: 2.9 +/- 2.3 mg/kg per day; p = < 0.005). With all feedings, alpha, Vu per kilogram, and Vf per kilogram were not related to gestational age, age at study, calcium intake, or each other. However, Vf per kilogram was inversely related to birth weight. Thus, alpha, Vu, and Vf appear to be independent and may be differentially affected by factors altering calcium dynamics. We conclude that increasing formula mineral content does not ensure increased retention; careful monitoring of individual infants remains indicated.

Calcium↗

High fiber diets slow bone turnover in young men but have no effect on efficiency of intestinal calcium absorption.

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Adult↗

Calcium kinetics in the hyperprostaglandin E syndrome.

Metabolic investigations, including the use of stable isotopes of calcium, were used to study calcium kinetics in three children with the hyperprostaglandin E syndrome. The studies were performed both during indomethacin treatment and in the absence of therapy. Off therapy, each child had hypercalciuria (mean urinary calcium excretion 0.478 mM/kg/d), hyperprostaglandinuria, and elevated serum calcitriol concentration. All had diminished bone density and were euparathyroid. Indomethacin treatment was associated with a marked reduction in serum calcitriol concentration, as well as decreased prostaglandin E excretion. Mean urinary calcium excretion fell to 0.135 mM/kg/d. The stable isotope studies defined two components to the hypercalciuria of this disease: an indomethacin-sensitive dietary contribution and a relatively indomethacin-resistant bone resorptive element. Bone densitometry confirmed the presence of the resorptive element by demonstrating skeletal demineralization.

Bone Density↗

Calcium absorption and metabolism in children with juvenile rheumatoid arthritis assessed using stable isotopes.

OBJECTIVE: To assess calcium intake, absorption, urinary excretion and the fraction of urinary calcium originating from bone and diet in patients with juvenile rheumatoid arthritis (JRA). METHODS: A dual tracer stable isotope technique was used to study 6 girls and 3 boys with JRA. RESULTS: Fractional absorption in the 6 girls, ages 4-9, with JRA was significantly lower than that in 10 similar, healthy girls (22.6 +/- 4.7% vs 30.4 +/- 8.4%, p = 0.033). Urinary calcium excretion tended to be higher in the girls with JRA than in controls, (2.9 +/- 1.5 vs 1.6 +/- 1.7, p = 0.15). The urinary calcium in patients with JRA was derived principally from bone, and there was no increase in diet derived urinary calcium. One of the boys with new onset JRA was markedly hypercalciuric and in negative calcium balance (-222 mg/day). CONCLUSION: Our data show that hypercalciuria in patients with JRA results from bone resorption, not hyperabsorption of dietary calcium and suggest that increases in calcium intake may benefit children with JRA.

Adolescent↗

Developmental changes in calcium kinetics in children assessed using stable isotopes.

Total exchangeable calcium pool size (TEP) and bone calcium accretion rate (Vo+) were measured using stable isotopes in healthy children and young adults. 42Ca or 46Ca was given intravenously to 10 children aged 10 months to 14 years and 3 women aged 23-33 years. Calcium kinetic parameters were determined using a two- or three-exponential curve of the resultant serum and urine tracer excesses. These data were compared with previously reported (radiotracer) kinetic studies of 21 children and 5 adults without known bone disease. Current results are comparable to those previously obtained, and the data from all studies were analyzed together. Total Vo+ was significantly greater in children aged 3-16 years than in adults (2.8 +/- 1.6 versus 0.7 +/- 0.2 g/day, p less than 0.01). Both TEP and Vo+ were significantly correlated to age independently of variations in body weight (p less than 0.01 for each). The ratio ko+ = Vo+/TEP was greater in children than adults (0.36 +/- 0.15 versus 0.12 +/- 0.03 day-1, p less than 0.001). These data demonstrate increased bone flow of calcium associated with increases in exchangeable calcium pools in children compared to adults. Vo+ and TEP may be maximum in early adolescence, associated with peak rates of net calcium accretion. The use of stable isotopes permits the safe evaluation of calcium kinetics in patients of all ages.

Adolescent↗

Pernicious anaemia as a risk factor for osteoporosis.

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51-76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51-79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P less than 0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r = 0.61, P less than 0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.

Achlorhydria↗

Electrospray mass spectrometry: application of ion evaporation theory to amino acids.

We describe the result of applying the ion evaporation theory to a series of amino acids. The very good correlation (r = 0.98) of the natural logarithms of protonated molecule intensities observed by electrospray with the difference between the hydration free energies of molecules and the gas-phase binding free energies of molecules and protons in amino acids is consistent with the ion evaporation model. It seems that the difference in the protonated molecule intensities of amino acids obtained by electrospray can be explained by a scheme in which protonated molecules in the liquid phase are extracted into the gas phase after a charged droplet is formed.

Amino Acids↗

Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action.

We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D, mean of four measurements per subject] increased with age by 22% (P less than 0.05) but, by split-point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [3H]1,25-(OH)2D3 kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25-(OH)2D. Despite the increase in serum 1,25-(OH)2D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P less than 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35% (P less than 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47% (P less than 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of intensities between doubly charged ions [M + 2H]2+ and singly charged ions [M + H]+ of gramicidin S by electrospray mass spectrometry.

The reason why the intensity of doubly charged ions [M + 2H]2+ of gramicidin S is higher than that of singly charged ions [M + H]+ in electrospray is investigated by ion evaporation theory. As a result of comparison between the total free energies of extracting [M + 2H]2+ and [M + H]+ from a charged droplet to infinity, it is found that the total free energy of [M + 2H]2+ is estimated to be lower than that of [M + H]+. This clearly supports the experimental result. In addition, the importance of the electrostatic contribution in electrospray is demonstrated by showing the result that the total free energy of [M + 2H]2+ without electrostatic contribution is higher than that of [M + H]+.

Gramicidin↗

Four interfaces for liquid chromatography/atmospheric-pressure-ionization mass spectrometry.

Mixture analyses are demonstrated using the liquid chromatograph/atmospheric-pressure-ionization mass spectrometric system with four modes. These modes are atmospheric-pressure spray with electron ionization, atmospheric-pressure chemical ionization, atmospheric-pressure spray ionization, and electrospray ionization modes. This system can deal with a wide variety of compounds from hydrocarbons with low polarity to proteins with high polarity.

Chromatography, Liquid↗

Stable isotopic measurement of endogenous fecal calcium excretion in children.

Using a stable isotopic technique in which 42Ca was administered via a bolus injection, we measured endogenous fecal calcium excretion, Vf, in five healthy children, aged 3-14 years. The Vf averaged 1.4 +/- 0.4 mg/kg/day, and was lower than urinary Ca excretion (Vu) in four of the five children. These results for Vf are consistent with previously reported results for Vf in healthy adults and much lower than those reported in premature infants. These results may be useful in understanding developmental changes in Ca metabolism and in interpreting dual tracer Ca isotope studies in children.

Adolescent↗