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Biomedical subjects

S A Atkinson

Publications and source records attributed to S A Atkinson.

At least 19 recordsLinked to original sources

Protein metabolism and growth of term infants in response to a reduced-protein, 40:60 whey: casein formula with added tryptophan.

The effects of an experimental reduced-protein (13 g/L), milk-based formula with a whey-casein ratio of 40:60 and added tryptophan (Trp) (490 mumol/L, or 100 mg/L; EF) were measured by growth and protein biochemistry in term infants from 0 to 12 wk postnatally. Newborn infants (n = 95) were randomly assigned to receive EF or conventional formula (15 g protein/L, whey-casein ratio of 60:40; CF) and compared with 58 breast-fed infants (BF). Growth velocity for weight, length, and head circumference was similar between groups. In 79 infants, blood was sampled preprandially at 4, 8, and 12 wk. For all times, plasma Trp was similar in BF and EF infants (58.4 +/- 10.4 vs 59.5 +/- 14.7 mumol/L, mean +/- SD) but lower in CF infants (53.4 +/- 8.4, P < 0.05). The plasma Trp-large neutral amino acid (AA) ratio was higher with EF than with CF, as was prealbumin (P < 0.05). Formula-fed infants had higher (P < 0.05) plasma urea, prealbumin, total essential AA, branched-chain AA, and threonine than did BF infants. A reduced-protein formula with added Trp resulted in Trp status similar to that in BF infants, without compromising growth or protein biochemistry compared with CF infants.

Amino Acids

Protein requirements and muscle mass/strength changes during intensive training in novice bodybuilders.

This randomized double-blind cross-over study assessed protein (PRO) requirements during the early stages of intensive bodybuilding training and determined whether supplemental PRO intake (PROIN) enhanced muscle mass/strength gains. Twelve men [22.4 +/- 2.4 (SD) yr] received an isoenergetic PRO (total PROIN 2.62 g.kg-1.day-1) or carbohydrate (CHO; total PROIN 1.35 g.kg-1.day-1) supplement for 1 mo each during intensive (1.5 h/day, 6 days/wk) weight training. On the basis of 3-day nitrogen balance (NBAL) measurements after 3.5 wk on each treatment (8.9 +/- 4.2 and -3.4 +/- 1.9 g N/day, respectively), the PROIN necessary for zero NBAL (requirement) was 1.4-1.5 g.kg-1.day-1. The recommended intake (requirement + 2 SD) was 1.6-1.7 g.kg-1.day-1. However, strength (voluntary and electrically evoked) and muscle mass [density, creatinine excretion, muscle area (computer axial tomography scan), and biceps N content] gains were not different between diet treatments. These data indicate that, during the early stages of intensive bodybuilding training, PRO needs are approximately 100% greater than current recommendations but that PROIN increases from 1.35 to 2.62 g.kg-1.day-1 do not enhance muscle mass/strength gains, at least during the 1st mo of training. Whether differential gains would occur with longer training remains to be determined.

Adult

Changes in human muscle protein synthesis after resistance exercise.

The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1-13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events.

Adult

Evaluation of protein requirements for trained strength athletes.

Leucine kinetic and nitrogen balance (NBAL) methods were used to determine the dietary protein requirements of strength athletes (SA) compared with sedentary subjects (S). Individual subjects were randomly assigned to one of three protein intakes: low protein (LP) = 0.86 g protein.kg-1.day-1, moderate protein (MP) = 1.40 g protein.kg-1.day-1, or high protein (HP) = 2.40 g protein.kg-1.day-1 for 13 days for each dietary treatment. NBAL was measured and whole body protein synthesis (WBPS) and leucine oxidation were determined from L-[1-13C]leucine turnover. NBAL data were used to determine that the protein intake for zero NBAL for S was 0.69 g.kg-1.day-1 and for SA was 1.41 g.kg-1.day-1. A suggested recommended intake for S was 0.89 g.kg-1.day-1 and for SA was 1.76 g.kg-1.day-1. For SA, the LP diet did not provide adequate protein and resulted in an accommodated state (decreased WBPS vs. MP and HP), and the MP diet resulted in a state of adaptation [increase in WBPS (vs. LP) and no change in leucine oxidation (vs. LP)]. The HP diet did not result in increased WBPS compared with the MP diet, but leucine oxidation did increase significantly, indicating a nutrient overload. For S the LP diet provided adequate protein, and increasing protein intake did not increase WBPS. On the HP diet leucine oxidation increased for S. These results indicated that the MP and HP diets were nutrient overloads for S. There were no effects of varying protein intake on indexes of lean body mass (creatinine excretion, body density) for either group. In summary, protein requirements for athletes performing strength training are greater than for sedentary individuals and are above current Canadian and US recommended daily protein intake requirements for young healthy males.

Adult

Efficacy of calcium glycerophosphate vs conventional mineral salts for total parenteral nutrition in low-birth-weight infants: a randomized clinical trial.

To test the efficacy of calcium glycerophosphate (CaGlyP) vs the conventional mineral salts, calcium gluconate plus KH2PO4 + K2HPO4 (CaGluc + P), in promoting mineral retention, 72-h mineral balance, biochemical status, net acid excretion, and growth were assessed in 16 low-birth-weight infants receiving total parenteral nutrition (TPN) containing approximately 1.5 mmol Ca and P.kg-1.d-1 for 5 d. Net retentions of calcium (1.2 +/- 0.2 vs 1.0 +/- 0.2 mmol.kg-1.d-1, means +/- SD) and phosphorus (1.1 +/- 0.3 vs 0.8 +/- 0.3 mmol.kg-1.d-1) from CaGluc + P vs CaGlyP, respectively, were similar, as were retentions of magnesium and sodium, urinary pH, and net acid excretion. Plasma ionized calcium, inorganic phosphorus, alkaline phosphatase, and osteocalcin were normal and not different between groups. CaGlyP is as effective as CaGluc + P in promoting mineral retention and normal mineral homeostasis. However, at intakes of less than or equal to 1.5 mmol Ca and P.kg-1.d-1 from either mineral salt, retention represented only 60% and 45%, respectively, of the predicted intrauterine accretion for calcium and phosphorus. Larger intakes permitted by the more-soluble CaGlyP may be desirable for infants receiving TPN.

Body Height

Contribution of sulfate and sulfoesters to total sulfur intake in infants fed human milk.

Colostrum (d 2-4) and mature human milk samples (d 23-30) collected from eight mothers giving birth at 31 +/- 7 wk of gestation were analyzed for total sulfur, free inorganic sulfate and acid labile sulfoesters. The data presented are representative of complete 24-h expressions. Total sulfur was measured using a wet digestion procedure in which all forms of sulfur were converted to inorganic sulfate. The sulfate was quantified by a radiometric barium precipitation assay. Total sulfur showed no marked diurnal variation, but the mean concentration in 19 colostrum samples (10.2 +/- 4.2 mmol/L) was significantly higher than in 14 mature milk samples (4.3 +/- 0.8 mmol/L) (P less than 0.001). The range of predicted 24-h intakes of sulfur by infants fed colostrum (0.78-3.22 mmol/kg body weight) was slightly higher than those fed mature milk (0.54-1.06 mmol/kg), but it was not significantly different. The combined fractions of free inorganic sulfate and acid-labile sulfoester fractions contribute less than 5% to the total sulfur content of either colostrum or mature milk. However, the physiological significance of these milk components remains to be determined.

Colostrum

The contributions of growth and puberty to peak bone mass.

Lumbar spine bone mass was measured by dual photon absorptiometry (DPA) in 236 subjects aged between 3 and 30 years. Expected values of bone mineral density (BMD) and bone mass (BMC) for the lumbar vertebrae L2 to L4 were derived as a function of age, by non-linear regression analysis. The selected regression equation was the sum of two logistic expressions, one of which was assigned to growth at the time of puberty and the other to the slower long term component of growth. Growth during puberty contributed about 50% of peak bone mass in females, while in males this contribution was closer to 15%. No increase was found in lumbar spine bone mass in females after puberty.

Absorptiometry, Photon

Whole body leucine metabolism during and after resistance exercise in fed humans.

The effects of resistance exercise upon leucine oxidation and whole body protein synthesis were studied using stable isotope methodology. L-[1-13C]leucine was used as a tracer to calculate leucine oxidation and whole body protein synthesis in six healthy, fed, male athletes in response to a 1 h bout of circuit-set resistance exercise. The measurements were performed prior to, during, and for 2 h after exercise, and corrections were made for background 13CO2/12CO2 breath enrichment and bicarbonate retention factor changes. Results demonstrated significant (P less than 0.01) increases in the background 13CO2/12CO2 breath enrichment at 1 and 2h after exercise and in the bicarbonate retention factor (P less than 0.01) during exercise. At 15 min after exercise, the bicarbonate retention factor was significantly (P less than 0.05) lower than at rest. There were no significant effects of exercise on leucine oxidation or flux, whole body protein synthesis, or the rate of appearance of endogenous leucine. We concluded that circuit-set resistance exercise did not affect the measured variables of leucine metabolism. In addition, large errors in calculating leucine oxidation and whole body protein synthesis during resistance exercise can occur if background 13CO2/12CO2 breath enrichment and bicarbonate retention factor changes are not accounted for.

Adult

Quantitation of free sulfate and total sulfoesters in human breast milk by ion chromatography.

A method for the assay of free sulfate and total sulfoesters in human breast milk by ion chromatography is described. After incubation in 1 M hydrochloric acid at 95 degrees C for 90 min, hydrolytic cleavage of sulfoester standards was essentially complete. The increase in free sulfate after hydrolysis was used as a measure of total acid-labile sulfoesters. We found that this fraction [222 +/- 16 mumol/l (mean +/- standard error), n = 29] comprised 87% of the total sulfate in mature milk. Free sulfate (35 +/- 3 mumol/l) therefore makes only a small contribution to the total sulfate pool available to human infants.

Chromatography, Ion Exchange

Bioavailability of urea nitrogen for the low birthweight infant.

Previous studies have demonstrated increased retention (40%) of dietary urea nitrogen by term infants recovering from infection compared to healthy infants (13%), possibly due to a higher requirement for nitrogen. Since low birthweight infants also have a high requirement for nitrogen, the bioavailability of urea nitrogen was investigated in low birthweight infants using 15N,15N-urea. Four low birthweight infants (gestational age = 30 +/- 2.2 weeks [mean +/- SD], birthweight = 1.4 +/- 0.3 kg) were fed formula enriched with 15N,15N-urea. Metabolic balance studies (72 hours) were performed with urine and fecal collections. Nitrogen was quantitated by Kjeldahl analysis and 15N,15N-urea by gas chromatography/mass spectrometry. Mean nitrogen intake was 489 +/- 32 mg/kg/d, with 75% nitrogen absorption and 62% nitrogen retention. Maximum urinary enrichment was 8%. Cumulative 15N,15N-urea excretion was 72%, resulting in 28% retention. Thus the bioavailability of urea nitrogen for low birthweight infants appears to be intermediate between compromised and normal term infants.

Biological Availability

Gender differences in substrate for endurance exercise.

The effects of gender on substrate utilization during prolonged submaximal exercise were studied in six males and six equally trained females. After 3 days on a controlled diet (so that the proportions of carbohydrate, protein, and fat were identical), subjects ran on a treadmill at a velocity requiring an O2 consumption of approximately 65% of maximal. They ran a total "distance" of 15.5 km with a range in performance time of 90-101 min. Plasma glycerol, glucose, free fatty acids, and selected hormones (catecholamines, growth hormone, insulin, and glucagon) were measured throughout and after the run by sampling from an indwelling venous catheter, and glycogen utilization was calculated from pre- and postexercise needle biopsies of vastus lateralis. Exercise protein catabolism was estimated from 24-h urinary urea nitrogen excretion over the test day and a nonexercise day. The males were found to have significantly higher respiratory exchange ratios (mean 0.94 vs. 0.87), greater muscle glycogen utilization (by 25%), and greater urea nitrogen excretion (by 30%) than the females. No gender differences were evident in the hormonal response to the exercise with the exception of a lower insulin concentration and a higher epinephrine concentration in the males. We conclude that, during moderate-intensity long-duration exercise, females demonstrate greater lipid utilization and less carbohydrate and protein metabolism than equally trained and nourished males.

Adult

Subcutaneous fat necrosis with hypercalcemia.

We report the case of an infant with diffuse subcutaneous fat necrosis following birth asphyxia who had hypercalcemia and the rare complication of venous calcification. The clinical and radiologic findings resolved over 5 months. The disease is characterized by the presence of painless subcutaneous nodules, mainly over bony prominences, possibly associated with hypercalcemia and calcification. Early identification of hypercalcemia will avert its serious sequelae.

Calcinosis

Abnormal zinc content in human milk. Risk for development of nutritional zinc deficiency in infants.

An abnormally low concentration of zinc in mother's milk has been associated with clinical nutritional zinc deficiency in premature and term newborns. Defective mammary gland secretion of zinc was suggested as the causative factor. We investigated whether low milk zinc concentration might be reflected in an abnormality of the distribution of zinc between casein, whey, and fat components of the milk, in a reduction in the levels of milk citrate, a zinc-binding ligand, or in abnormal levels of copper and iron. Milk from mothers of four low-birth-weight infants was identified as being deficient in zinc content for the lactational stage. One infant had clinical signs of nutritional zinc deficiency. For two of the three infants with subclinical deficiencies in whom balance study data were available, the apparent zinc balance was negative (-5.7 and -6.0 mumol/kg per day). These milks were examined for content and distribution of zinc, copper, and iron, and citrate concentration. Although total zinc concentration (4.5 to 17.2 mumol/L) was below the 95% prediction interval (15.2 to 59.7 mumol/L) for the lactational stage, the distribution of zinc was normal between milk components. Levels of citrate (1.46 to 5.13 mmol/L) were also within normal limits, as were levels of copper (0.27 to 0.85 mumol/L and iron (0.41 to 1.13 mumol/L). We concluded that there was no indirect evidence of a secretory abnormality in milk zinc deficiency, but speculated that there might instead be an abnormality of zinc uptake by the mammary gland from the plasma.

Breast Feeding

Partition of nitrogen intake and excretion in low-birth-weight infants.

Although nitrogen balance studies have been carried out in low-birth-weight infants, few have partitioned the nitrogen into its components. In this study, 72-hour balance studies were conducted in 24 low-birth-weight infants (gestational age, 30.7 +/- 1.6 weeks; birth weight 1.36 +/- 0.25 kg) fed their mothers' milk (preterm milk) or 50% preterm milk and 50% formula. Total nitrogen, nonprotein nitrogen, and whey protein intake and excretion were measured. Total nitrogen intake (preterm milk group, 452 +/- 138 mg/kg per day; preterm + formula group, 406 +/- 93 mg/kg per day), absorption (85%), and retention (71%) were not significantly different between groups. Intact and fragments of secretory IgA and lactoferrin were detected in soluble fecal extracts, and represented 25% and 9% of intake, respectively. Feeding preterm milk allows for nitrogen accretion similar to intrauterine growth rates for 5 weeks postnatally, and provides potentially functional proteins for the low-birth-weight infant.

Birth Weight

Mineral homeostasis and bone mass in children treated for acute lymphoblastic leukemia.

Clinical observations of bone pain, abnormal gait, and unusual fractures during remission of leukemia led us to assess mineral status in a cohort of 16 children with acute lymphoblastic leukemia treated with intensive chemotherapy. During maintenance and 6 months after the completion of therapy, blood and urine were analyzed for calcium and magnesium and blood for osteocalcin, vitamin D, and parathyroid hormone. Bone mineral content and bone width of the distal one third of the radius of the nondominant arm was measured by single-photon absorptiometry. During therapy, mild ionic hypocalcemia (less than 1.19 mmol/L) and hypomagnesemia (less than 0.77 mmol/L) were demonstrated in 9 and 8 of 16 children, respectively; hypercalciuria (8/16) and hypomagnesiuria (12/16) were also observed. Plasma osteocalcin values correlated with plasma magnesium levels (r = 0.54; p less than 0.05). Oral magnesium supplements normalized plasma magnesium, calcium, and osteocalcin levels, all of which were normal at the postchemotherapy study. Plasma 1,25-dihydroxyvitamin D levels were nondetectable (less than 8 ng/ml) in 12 of 13 patients receiving therapy and in 7 of 14 patients not receiving therapy; alkaline phosphatase activity increased significantly after therapy (179 +/- 86 to 340 +/- 101 units/L), and parathyroid hormone levels were normal in both studies. Bone mineral content/bone width ratio was less than 1 SD below the mean for age- and sex-related population standards in 70% of patients. These data indicate that alterations in magnesium, calcium, and vitamin D metabolism in children treated for acute lymphoblastic leukemia may be instrumental in inducing or sustaining altered bone turnover during chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

In vitro solubility of calcium glycerophosphate versus conventional mineral salts in pediatric parenteral nutrition solutions.

Low-birth-weight infants requiring total parenteral nutrition receive inadequate intakes of calcium (Ca) and phosphorus (P) due to poor solubility of available mineral salts. To optimize Ca/P delivery, we tested the effects on in vitro solubility of mineral salt:calcium glycerophosphate (CaGP) versus calcium gluconate and K2HPO4 (CG + P); Ca:P ratios of 1:1 (at 12.5 and 25 mmol/L of Ca and P) and 2:1 (25:12.5 mmol/L); amino acid (AA) formulation: Aminosyn (A), Aminosyn-PF (A-PF), TrophAmine (T) or Vaminolac (V); and AA concentration (25 versus 8.3 g/L). Parenteral nutrition solutions contained 10% dextrose and vitamins and minerals typical of a neonatal prescription. Solutions were sampled at preparation, after 24 h in the neonatal unit (25 degrees C), and from before and after a 0.22-micron filter in extension tubing through which solutions were pumped at 5 ml/h within an incubator at 37 degrees C. Samples were analyzed for Ca and pH, and precipitation by spectrophotometry at 600 nm and light microscopy at x 100 magnification. The Ca concentration was unaffected by filtration. While spectrophotometry detected only gross precipitation, with light microscopy crystal formation was evident with 25 mmol/L of Ca and P as CG + P in A and T at 25 g of AA/L and in A, V, T, and A-PF at 8.3 g of AA/L. Precipitation did not occur with CaGP or CG + P at 12.5 mmol/L of Ca and P. Under in vitro conditions mimicking the neonatal unit, CaGP versus CG + P resulted in greater mineral solubility even at low AA concentrations.

Amino Acids