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Biomedical subjects

S A Abrams

Publications and source records attributed to S A Abrams.

At least 73 records · Page 4Linked to original sources

Precise determination of the absorptive component of urinary calcium excretion using stable isotopes.

Some patients with hypercalciuria are thought to have enhanced enteric calcium absorption, with a major component of recent diet contributing to urinary calcium. This mechanism has been difficult to test with the usual calcium loading procedures. We employed dual stable calcium isotope tracers to quantitate the components of urinary calcium excretion in 38 healthy female children. The mean urinary calcium excretion in these girls was 2.4 mg/kg per day. The contribution of recent diet to this total was a mean of 0.2 mg/kg per day. The maximum dietary contribution to urinary calcium excretion was 0.86 mg/kg per day. Recent diet contributes a mean of 8% to total dietary calcium excretion. This novel method permits precise quantitation of the contributions of recent diet and tissue stores to urinary calcium excretion. In these healthy girls, the fraction of urinary calcium derived from diet is trivial.

Absorption↗

Postnatal attainment of intrauterine macromineral accretion rates in low birth weight infants fed fortified human milk.

HYPOTHESIS: Provision of more bioavailable mineral sources as human milk supplements enables very low birth weight (VLBW) infants to meet the intrauterine accretion rate for calcium and phosphorus. DESIGN: Comparison of currently formulated human milk fortifier with previous formulation. SETTING: Neonatal level II and III nurseries. PATIENTS: Twenty-six healthy, VLBW infants, whose mothers chose to breast-feed. INTERVENTIONS: We tested the effects of two formulations designed for VLBW infants as human milk supplements and differing primarily in their quantity and source of Ca, P, and magnesium. The study interval began with a milk intake of 100 ml.kg-1.day-1 and ended when a body weight reached 2.0 kg. MAIN OUTCOME MEASURES: Net absorption and retention of Ca, P, and Mg during a nutritional balance study conducted once during the study interval, growth during the entire study interval, and bone mineral content of the radius were measured at the beginning and end of the study interval. RESULTS: The newer Ca gluconate-glycerophosphate preparation (given to group CaGP) resulted in greater net absorption and retention of Ca and P (p < 0.01) than in infants given Ca phosphate (group CaTB). Mg retention was greater than (in group CaGP) or equivalent to (in group CaTB) the intrauterine accretion rate. Radius bone mineral content was significantly greater in group CaGP than in group CaTB (p < 0.001). Volumes of the fortified human milk preparation needed to meet the needs for gain in body weight were higher in group CaGP than in group CaTB (p < 0.001). CONCLUSIONS: Intrauterine accretion rates for Ca and P can be achieved when VLBW infants are fed human milk supplemented with Ca gluconate-glycerophosphate. Supplementation of human milk with Mg may not be indicated. In this study, greater intakes of Ca and P, and not improvements in bioavailability, result in improved net retention and bone mineral content of VLBW infants.

Absorption↗

A three-hour measurement to evaluate bone calcium turnover.

It is well established that short-term clearance of an intravenous calcium load in vivo reflects bone uptake. Using results from isotope-dilution experiments with 42Ca, a 3-h test has been developed to measure a quantity, gamma, related to bone accretion. This test is proposed as a useful, clinically applicable measure of bone status. For early times, t, after a bolus of 42Ca, plasma tracer dilution was well approximated by t-gamma, where gamma is related to the fractional rate of loss of tracer, q, from blood into bone (1/q)(dq/dt) = -gamma/t). Gamma was evaluated from kinetic measurements on 91 normal female children, adolescents, and adult women in the age range 4-50 years. For t < or = 3 h, all clearance curves were well fit by a power function. Gamma was found to vary from 0.244 +/- 0.031 for adult premenopausal women (N = 22) to 0.392 +/- 0.056 for prepubertal children (N = 29). Using the Spearman rank-order correlation test, gamma was correlated with bone accretion measured from classic calcium kinetic studies with a correlation coefficient of 0.721, significant at p < 0.005. In those cases in which accretion and resorption remain tightly linked, gamma also provides information on the state of calcium loss from bone. Gamma was evaluated in 14 subjects with bone disease characterised by increased resorption (osteoporosis, Paget's disease) and in 27 subjects with decreased accretion (osteogenesis imperfecta, types I, III, IV; steroid-treated juvenile dermatomyositis). All subjects with Paget's disease and with osteoporosis showed increased gamma, consistent with high bone turnover. The osteoporotic patients furthermore exhibited gamma increasing monotonically by approximately 1% per year after age 55.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Use of stable isotopic tracers in studies of whole body calcium metabolism.

Stable isotopic tracers of calcium have been used to characterize the absorption of dietary calcium and the subsequent distribution of this element through the body. For a group of 7 healthy children, ages 4-14, and 7 children with osteogenesis imperfecta (OI), types I, III and IV, ages 6-17, there were no detectable differences in the fractional absorption of dietary calcium, 0.29+/-0.11 and 0.28+/-0.16, respectively. The total exchangeable pool of calcium was found to be 161+/-52 mg/kg for the healthy children and 95+/-29 mg/kg for the 3 children with Type I OI, 250+/-75 mg/kg for the 3 children with Type III OI and 216 mg/kg for the child with Type IV OI.

Administration, Oral↗

Effects of development on techniques for calcium stable isotope studies in children.

We evaluated the effects of age and pubertal status on the tracer excess measured in urine samples collected during the 120 h after the oral and intravenous administration of calcium stable isotopes to 90 children (16 preterm infants and 74 females aged 4.9-16.8 years). Analysis of subjects shows differences in distribution volume and fractional absorption of calcium based on developmental status, with four separate groups being identified. These are: (i) premature infants; (ii) prepubertal girls (Tanner stage 1); (iii) early pubertal girls (Tanner states 2-3); and (iv) late pubertal girls (Tanner stages 4-5). Identification of groups in this fashion allows for adequate dosing in calcium stable isotope studies, with the minimum dose being given to achieve an increase in urinary isotopic content consistent with the precision of the analytical equipment.

Adolescent↗

Application of magnetic sector thermal ionization mass spectrometry to studies of erythrocyte iron incorporation in small children.

The optimal evaluation of iron metabolism requires the administration of two isotopes of iron. However, high-precision measurement of isotopic ratios from blood samples obtained after administration of two stable isotopes of iron to human subjects has not previously been reported. Using a cation-exchange system to isolate iron from blood samples, we found that high-precision (< 0.2%) measurements of 58Fe/56Fe and 57Fe/56Fe could be performed using magnetic sector thermal ionization mass spectrometry. Clinical studies in four 1-year-old infants showed that this technique could be used to demonstrate a lower rate of iron absorption in small children given an iron supplement (57Fe) with milk compared to those given iron (58Fe and ferrous sulfate) with ascorbic acid. This technique will enable the evaluation of iron metabolism in populations in whom the use of radioactive iron tracers is not appropriate.

Adolescent↗

Extraction of magnesium from biological fluids using 8-hydroxyquinoline and cation-exchange chromatography for isotopic enrichment analysis using thermal ionization mass spectrometry.

The use of 8-hydroxyquinoline to precipitate magnesium was evaluated as a method for preparing biological samples for isotopic enrichment analysis using thermal ionization mass spectrometry (TIMS). Standard curves in matrices of water, serum, and urine were prepared using varying amounts of 25Mg. The 25Mg/24Mg isotope ratio was measured by TIMS using a silica gel/phosphoric acid technique. Although the total Mg recovered by precipitation from the matrices varied considerably and was dependent on matrix, recovery was sufficient for isotopic enrichment analysis. Urine samples required cation-exchange chromatography (Bio-Rex AG 50W-X8 filter membrane, Bio-Rad Laboratories) prior to precipitation to remove contaminants which interfered with the thermal ionization process. The observed versus expected 25Mg/24Mg enrichments were evaluated using linear regression analysis: water, y = 0.016 + 1.022x; serum, y = 0.5 + 1.097x; urine, y = -0.004 + 0.943x. This method has proven useful for the isolation of magnesium from the biofluids tested.

Body Fluids↗

A non-Markovian model for calcium kinetics in the body.

We present a new generalized compartmental model for calcium kinetics as measured by tracer concentration in blood plasma. The parameter measuring incorporation of calcium in bone discriminates between different levels of physical development in female teenagers and between teenagers and adults.

Adolescent↗

Calcium kinetics in lactating women with low and high calcium intakes.

Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption.

Adult↗

Calcium metabolism in girls: current dietary intakes lead to low rates of calcium absorption and retention during puberty.

We evaluated the effects of self-selected diets on calcium absorption and calculated retention in girls during pre-, early, and late puberty. Dietary calcium absorption was measured in 51 girls aged 4.9-16.7 y by using a dual-tracer stable-isotope technique. We found that calcium intake was similar among girls of all ages and all degrees of pubertal development and was below the recommended dietary allowance (1200 mg/d) for 21 of 25 girls aged > or = 11 y. The early pubertal period was associated with a higher percent of dietary calcium absorption (34.4 +/- 11.9%) than was the prepubertal (27.7 +/- 8.2%) or late pubertal periods (25.9 +/- 7.8%). Calculated calcium retention averaged 132 +/- 83 mg/d in prepubertal girls, 161 +/- 88 mg/d in early pubertal girls, and 44 +/- 91 mg/d in late pubertal girls. Peak calcium retention during early puberty was far below that previously reported after higher calcium intakes. We conclude that peak periods for calcium retention for girls are in the pre- and early pubertal periods. The current calcium intake of American girls during the pubertal growth period may not enable maximal mineral retention; therefore, increased calcium intakes should be considered.

Adolescent↗

Determination of fractional absorption of dietary calcium in humans.

Four dual-isotopic label methods for determining true fractional absorption of dietary calcium were compared in 23 subjects. The ratio of the integrals of oral label in a 24-h pooled urine to intravenous label in the same urine is called alpha 24h and was taken as the standard against which the others were compared. alpha Spot is the ratio of the fraction of oral label to the fraction of intravenous label in a single urine specimen; alpha Lag is the ratio of the level of oral label in blood 4 h after administration to the level of intravenous label in blood 2 h after administration. alpha Dec is obtained by deconvoluting response to the intravenous label from the response to the oral tracer. Results were as follows: alpha 24h = 0.273 +/- 0.124, alpha Dec = 0.300 +/- 0.101 (n = 14), alpha Spot = 0.359 +/- 0.179, and alpha Lag = 0.271 +/- 0.103. The Bland-Altman approach for comparison of methods was used to show that results for alpha Spot and alpha Lag can be expected, with a 95% confidence limit, to differ from the value of alpha 24h by 60 and 69%, respectively. The results for alpha Dec were shown to be not only indistinguishable from alpha 24h but identical from a theoretical perspective.

Administration, Oral↗

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↗

Mineral metabolism in children with dermatomyositis.

OBJECTIVE: To measure calcium metabolism in 12 children with juvenile dermatomyositis (JDM). METHODS: We used dual-tracer stable isotope studies to measure calcium metabolism in 12 children with JDM and a group of 43 healthy children (Group HC) of similar ages. Five of the JDM subjects were receiving steroids (Group JDM-ST) and 7 were not (Group JDM-NS). RESULTS: The rate of calcium absorption in Group JDM-ST was lower than that in Group HC (19 +/- 10% vs 30 +/- 11%, p < 0.05). The lower rate of absorption was associated with a net loss of calcium each day (calculated calcium retention, Vbal, of -35 +/- 14 mg/day compared to +140 +/- 97 mg/day in Group HC, p < 0.01). Group JDM-NS showed slightly lower calcium absorption than Group HC and significantly lower Vbal (+33 +/- 70 mg/day, p < 0.01 vs Group HC) than Group HC. Group JDM-ST subjects also had decreased bone calcium deposition rates. CONCLUSION: Patients with JDM may be at risk for significant loss of bone mineral associated with decreased calcium absorption, especially in the acute phase of their disease when they are receiving steroid therapy.

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↗