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Guillain-Barre syndrome (GBS) is a randomly acquired inflammatory disease that affects approximately 2 persons in 100,000 annually. There have been no discriminating risk factors identified including age, sex, or race. The syndrome results in the demyelination of peripheral nerves, which leads to progressive motor weakness and paralysis. The critical care nurse should gain from this article an overview of Guillain-Barre syndrome during the acute phase. Included is the pathophysiology of the syndrome, clinical presentation, acute phase nursing assessment and management, and currently available treatment options.

Purpose Treatment for acute lymphoblastic leukemia (ALL) in childhood results in a reduction in bone mineral density (BMD). Whether there is a recovery of this lost bone mass in survivors of ALL is not known. We sought to determine if changes in BMD are common long-term sequelae in children with ALL. Methods Bone mineral densitometry of the lumbar spine and femoral neck was performed on 106 patients. The results were compared with those of age-matched normal controls. The effect of treatment was examined in those with low BMD compared with the remainder of the study group. Results When data were tested with respect to age, sex, and age and sex, no difference was observed in BMD between survivors of childhood ALL and controls. In the subgroup of patients with low BMD, the difference was not related to age, age at diagnosis, or years since diagnosis. Low BMD of the spine was not explained by radiotherapy (RT), methotrexate (MTX) dose, or corticosteroid dose. Low BMD of the femur was not explained by RT. However, those with low femoral BMD were more likely to have received high-dose MTX or higher-dose corticosteroids compared with the remainder of the group. Conclusion It appears that survivors of childhood ALL as a whole recover normal BMD. However, those patients who received a total MTX dose of greater than 40,000 mg/m2 or a total corticosteroid dose of greater than 9,000 mg/m2 may not recover normal BMD and therefore should be screened for decreased BMD of the femoral neck.

Body weight, height and lumbar spine bone mineral density (BMD) were measured in 40 children (27 male, 13 female, aged 0.3-17.0 years) with acute lymphoblastic leukemia (ALL) at diagnosis and 6 months after initiation of chemotherapy, and in 40 age- and sex-matched local healthy children. Serum and urinary biochemical indices of mineral metabolism were measured in the children with ALL at both time points. From diagnosis to 6 months, a reduction in the fractional excretion of magnesium was found. Serum osteocalcin was low at diagnosis and increased during chemotherapy, whereas 24-h urinary type I collagen cross-linked N-telopeptide was unchanged. The Z-scores for lumbar spine BMD increased and were correlated with the serum osteocalcin at 6 months. The change in serum magnesium was correlated negatively with the change in lumbar spine BMD, and with the lumbar spine BMD Z-score at 6 months. After initiation of treatment for ALL, rapid recovery in bone formation, which results in the movement of extracellular magnesium into the skeleton through bone formation, may be an important contributor to hypomagnesemia.

Body weight, height and lumbar spine bone mineral density (BMD) were measured in 40 children (27 male, 13 female, aged 0.3-17.0 years) with acute lymphoblastic leukemia (ALL) at diagnosis and 6 months after initiation of chemotherapy, and in 40 age- and sex-matched local healthy children. Serum and urinary biochemical indices of mineral metabolism were measured in the children with ALL at both time points. From diagnosis to 6 months, a reduction in the fractional excretion of magnesium was found. Serum osteocalcin was low at diagnosis and increased during chemotherapy, whereas 24-h urinary type I collagen cross-linked N-telopeptide was unchanged. The Z-scores for lumbar spine BMD increased and were correlated with the serum osteocalcin at 6 months. The change in serum magnesium was correlated negatively with the change in lumbar spine BMD, and with the lumbar spine BMD Z-score at 6 months. After initiation of treatment for ALL, rapid recovery in bone formation, which results in the movement of extracellular magnesium into the skeleton through bone formation, may be an important contributor to hypomagnesemia.

Provision of the bone minerals and vitamin D as fortificants in food or as dietary supplements designed for older infants and toddlers in Latin America is likely to be beneficial and safe. Currently available data are inadequate to establish the precise amounts of these nutrients that would be required for such a supplement. These amounts would vary according to the local base diet. However, reasonable estimates can be made on the basis of current dietary recommendations as well as existing data on bioavailability and customary intake. The strongest case can be made for calcium and vitamin D supplementation. Because excessive dietary calcium can reduce zinc absorption as a result of interactive effects within the intestine, an appropriate ratio of calcium to zinc should be used, even if this means adding zinc as a fortificant or supplement. Magnesium supplementation may be appropriate in some circumstances but it cannot be routinely advocated at present. It is unlikely that phosphorus supplementation is needed for most population groups because of the relatively high usual dietary phosphorus intakes, primarily from phosphate salts added to carbonated beverages and as food preservatives.

Diminished bone mass (osteopenia) is recognized increasingly as a consequence of therapy in survivors of cancer in childhood. It has been reported in two small series of survivors of Wilms tumor. The objectives of this study were to explore, in a larger sample of such subjects, the prevalence of osteopenia and a possible relationship between osteopenia of the lumbar spine and abdominal irradiation. All survivors of Wilms tumor (n=49) in a single institution were considered eligible for study. Thirty-one agreed to participate; the non-participants were not notably different in their demographic characteristics and diseases/treatment experience. Information was obtained about prior treatment, and usual diet, sun exposure and physical activity. Bone mineral content was measured by dual energy X-ray absorptiometry, and biochemical markers of bone turnover, calciotropic hormones and minerals were assessed in a single blood sample. By Z-scores of whole body bone mineral content, 8 subjects were osteopenic. This was unrelated to milk intake or sun exposure and was not more common in the lumbar spine of those who had been irradiated (15/31 subjects). Physical activity correlated positively with bone mineral density Z-scores (p

Diminished bone mass (osteopenia) is recognized increasingly as a consequence of therapy in survivors of cancer in childhood. It has been reported in two small series of survivors of Wilms tumor. The objectives of this study were to explore, in a larger sample of such subjects, the prevalence of osteopenia and a possible relationship between osteopenia of the lumbar spine and abdominal irradiation. All survivors of Wilms tumor (n=49) in a single institution were considered eligible for study. Thirty-one agreed to participate; the non-participants were not notably different in their demographic characteristics and diseases/treatment experience. Information was obtained about prior treatment, and usual diet, sun exposure and physical activity. Bone mineral content was measured by dual energy X-ray absorptiometry, and biochemical markers of bone turnover, calciotropic hormones and minerals were assessed in a single blood sample. By Z-scores of whole body bone mineral content, 8 subjects were osteopenic. This was unrelated to milk intake or sun exposure and was not more common in the lumbar spine of those who had been irradiated (15/31 subjects). Physical activity correlated positively with bone mineral density Z-scores (p0.005). Normal bone formation was reflected in normal blood levels of osteocalcin. C-telopeptide levels, reflecting bone resorption, were high but approximately correlated inversely with maturity. Low serum magnesium and parathyroid hormone levels were detected in a minority of subjects. Osteopenia is present in a large minority (27%) of survivors of Wilms tumor, and an imbalance of bone turnover (with excessive resorption) may be common. Irradiation does not appear to play a causal role. It is possible that a subtle renal tubular defect exists in these individuals; a prospect worthy of further exploration.

Vitamin D status and its relation to a myriad of health outcomes is a current “hot” topic in clinical medicine. Thus, Hanson and colleagues’ randomized trial of 400 IU/day of vitamin D vs placebo in newborn infants is timely (1). As background to the discussion of this paper, it is relevant to review the basis of the recent recommendations for vitamin D for infants from the Dietary Reference Intakes (DRIs) (2). Somewhat surprisingly, the DRIs were not mentioned in the paper by Hanson and colleagues (1), but rather only the recommendation for vitamin D intakes in infants by the American Academy of Pediatrics (AAP) (3). Although the recommendation of 400 IU vitamin D per day is consistent between the DRIs and AAP, the DRIs offer a more substantive basis for the recommendation. First, it must be recognized that the DRI values for infants younger than 6 months of age are intended for term-born, healthy, breastfed infants who are considered the model for normal infant growth. For most nutrients, the DRIs for infants are based on the composition of breast milk (plus estimated intake from foods after 6 months of age), but this was not possible for vitamin D, which is found in low concentration in human milk. Because existing data precluded setting an Estimated Average Requirement for infants, an Adequate Intake (AI) for vitamin D of 400 IU per day was set for infants age 0 to 12 months (2). This was based on this intake being associated with maintenance of serum 25hydroxyvitamin D (25[OH]D) at more than 12 ng/mL (30

This report summarizes a meeting, Obesity Prevention from Conception, held in Ottawa in 2012. This planning workshop was funded by the Canadian Institutes of Health Research (CIHR) to bring together researchers with expertise in the area of maternal obesity (OB) and weight gain in pregnancy and pregnancy-related disease to attend a one-day workshop and symposium to discuss the development of a cross-Canada lifestyle intervention trial for targeting pregnant women. This future intervention will aim to reduce downstream OB in children through encouraging appropriate weight gain during the mother's pregnancy. The workshop served to (i) inform the development of a lifestyle intervention for women with a high pre-pregnancy body mass index (BMI), (ii) identify site investigators across Canada, and (iii) guide the development of a grant proposal focusing on the health of mom and baby. A brief summary of the presentations as well as the focus groups is presented for use in planning future research.

Seven-day-old male Yorkshire piglets were randomized to receive either dexamethasone (DEX) 0.5 mg/kg/day or placebo (water) for 15 days (n = 8/group). Body weight and length, plasma intact parathyroid hormone (PTH), N-Mid osteocalcin and C-terminal telopeptide of type I collagen (CTx) were measured at baseline and end of the study. The indices of bone metabolism did not differ between DEX and placebo groups at baseline. At the end of the study, plasma intact PTH was increased (p < 0.01) and N-Mid osteocalcin (p < 0.01) and CTx (p < 0.01) were decreased from baseline value in the DEX group but not in the placebo group. The reduction (Z-score) in N-Mid osteocalcin was greater than that in CTx (p < 0.05). We conclude that exogenous DEX in young piglets stimulates a rise in circulating intact PTH. Both circulating CTx and osteocalcin are reduced with the decline in osteocalcin greater than that in CTx.

Summary: Purpose: To determine whether long-term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism. Methods: Twenty-seven boys and 26 girls, aged 3 to 17 years (9.2 ± 3.9, mean ± SD), with epilepsy treated with VPA and/or LTG for ≥2 years were evaluated for growth, nutrient intakes, physical activity, bone mineral density (BMD), and blood biochemical indices of mineral and bone metabolism. Results: Twenty-three (43.4%) of the children had a body height below the 10th percentile. Z-scores for BMD below –1.5 occurred in 24.4% of the children. When patients were divided into two groups according to daily activity score, a significantly lower Z-score for total body BMD (p = 0.007), percentile for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04), osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in the inactive compared with the active group. Z-score for total body BMD was correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02). Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body height were found in the VPA-plus-LTG treatment group. Conclusions: Long-term VPA and LTG therapy, particularly when combined, is associated with short stature, low BMD, and reduced bone formation. These alterations may be mediated primarily through reduced physical activity rather than through a direct link to the VPA and/or LTG therapy.

Objective To determine if supplementary structured breastfeeding counseling (SSBC) for both parents compared with conventional hospital breastfeeding support (CHBS) improves the duration of breastfeeding in very low-birth-weight infants up to 1 year old. Design Randomized trial with longitudinal follow-up of infants at term, and ages 1, 3, 6, and 12 months (infant ages corrected for prematurity). Setting A tertiary-level neonatal intensive care unit (NICU) and geographically defined region in central-west Ontario, Canada. Participants Parents of infants with a birth weight less than 1500 g, who planned to breastfeed. Interventions The SSBC consisted of viewing a video on breastfeeding for preterm infants; individual counseling by the research lactation consultant; weekly personal contact in the hospital; and frequent postdischarge contact through the infants' first year or until breastfeeding was discontinued. The CHBS group had standard breastfeeding support from regular staff members confined to the period of hospitalization in the NICU. Main Outcome Measure Duration of breastfeeding. Results At study entry, there were no statistically significant differences in major demographic characteristics between groups. The mean duration of breastfeeding was 26.1 weeks (SD = 20.8; median, 17.4) in the SSBC group and 24.0 weeks (SD = 20.5; median, 17.4) in the CHBS group (not statistically significant). Conclusions Long-term breastfeeding counseling of parents of very low-birth-weight infants in this study did not demonstrate a significant difference in duration of breastfeeding. These results may be explained by the high motivation to breastfeed in both groups, a relatively advantaged population, and the availability of community breastfeeding resources, which may have diminished any significant differences that could have resulted from a breastfeeding intervention. The results of this study, compared with previous studies of very low-birth-weight infants, indicate a new trend to longer duration of breastfeeding in preterm infants.

Interactions between metals of similar coordination chemistry are of relevance to infant nutrition due to the highly variable metal:metal ratios found in formulas. Using ratios similar to those found in infant formulas, our objectives were to determine the effects of metals and of lactose and other saccharides on Zn 12 transport across intestinal brush border membranes. Brush border membrane vesicles prepared from intestines of 5 preweaned piglets were used to determine whether Ca 12 ,M g 12 ,F e 12 ,C u 12 ,C d 12 ,o r Mn 12 would antagonize Zn 12 uptake. 65 Zn 12 uptake by brush border membrane vesicles was measured over 20 min with metal concentrations constant, and at 1 min with increasing metal concentrations. Zn 12 bound to the external surface of vesicles was removed with ethylenediamine-tetraacetic acid. Lactose induced Zn 12 uptake to a greater extent than glucose polymer, whereas maltose, galactose, or galactose/glucose had no effect. Over 20 min, a 10:1 concentration of Fe 12 ,C d 12 ,C u 12 , and Mn 12 lowered Zn 12 uptake significantly (P , 0.05). Higher concentrations of divalent cation significantly lowered Zn 12 (0.2 or 0.1 mM) uptake for all metals tested (P , 0.05), except for Mn 12 (0.1 mM Zn 12 ). Inhibition constant determination quantified relative competitive potential with Mg 12 , Ca 12 ,, Mn 12 , Fe 12 , Zn 12 ,, Cu 12 . Relative amounts of Ca 12 ,M g 12 , and Fe 12 similar to those found in infant formulas reduced Zn 12 uptake by at least 40%. Our data demonstrate that dietary minerals compete during brush border membrane transport, and may help explain antagonistic mineral interactions observed in vivo. Divalent metal concentrations and lactose content of milk affect zinc absorption in neonates and must be carefully considered in formula design. © 2001 Elsevier Science Inc. All rights reserved.

There is increasing evidence that feeding of mother's milk to very low-birth weight and extremely low-birth weight infants has both immediate and long-term benefits to growth and development of this vulnerable infant population. Although clinically mother's milk is increasingly the feeding of choice for tiny premature infants for the healthcare provider, this practice presents challenges such as: careful collection and storage of the milk in order to preserve the native milk nutrients and immune factors; identification of the need for fortification of mother's milk with single or multiple nutrients to ensure optimal growth and normal biochemical status (such as plasma sodium, phosphorus, and protein); and achievement of successful transition for gavage feeding of expressed milk to suckling by the tiny premature infant. Although initial growth and bone mass accretion may be slower in infants fed mother's milk compared with those infants fed formula, current evidence suggests that catch-up growth occurs. The potential for benefits of human milk feeding in early life for neurodevelopment and protection against infections must be weighed against any possible detrimental effects of slower growth in early life.

Aim: To characterize the ontogeny of circulating IGF-I, the IGF binding proteins (IGFBPs) and biochemical markers of bone turnover in dexamethasone (DEX)-treated preterm infants with chronic lung disease. Methods: Plasma and urine samples from 17 infants were obtained prior to DEX, after 9–12 days of DEX and 10 days after the completion of DEX to assess plasma IGF-I, IGFBPs, osteocalcin and urinary N-telopeptide. Nutrient intakes and growth were monitored from birth until term corrected age at which time body composition was evaluated by dual energy X-ray absorptiometry. Results: Although nutrient intakes did not differ during or after DEX, weight gain (115 vs. 174 g/week) and length gain (0.7 vs. 1.0 cm/week) were higher after DEX treatment. Plasma IGF-I, IGFBP-3 and osteocalcin increased over time. N-telopeptide was the only biochemical parameter which appeared to be suppressed during DEX (1342 nM bone collagen equivalents/mM creatinine vs. 2486 (pre-DEX) and 2292 (post-DEX)). At term corrected age, bone mineral content was lower in dexamethasone-treated infants compared to preterm and term reference infants. Conclusion: Changes in circulating IGFBP-2 and IGFBP-3 paralleled the changes reported in non-steroid-treated infants; however, it remains uncertain whether the natural rise in IGF-I was suppressed by DEX treatment. Assessment of these circulating components provided limited insight into the mechanisms by which DEX alters growth and bone turnover.

Although we appreciate the comments of Chotirmall et al, we do not have the evidence in our data to support their suggestion of an independent bone phenotype. The majority of our patients had suboptimal 25-hydroxyvitamin D (25-OHD) and vitamin K …

The objective of this investigation was to describe zinc status to 12 months corrected age in premature infants fed their mother's milk in relation to nutritional management in hospital and post-hospital discharge. Twenty-five premature infants fed their mother's milk in hospital were randomized to receive either a multi-nutrient fortifier (MNF), providing protein, calcium, phosphorus and zinc (MM + MNF) or calcium and phosphorus alone (MM + CaGP). Twelve preterm infants fed a preterm formula (PTF) served as a comparison group. At 35 weeks post-menstrual age zinc retention was determined using the stable isotope tracer 70Zn. After hospital discharge infants in MM + MNF and MM + CaGP were designated to a mother's milk-feeding group to 6 months corrected age (Post-MM) or formula feeding group (Post-FF) based on parental choice of feeding practice. Anthropometry was performed at term, three, 6 and 12 months corrected age. At 6 and 12 months corrected age a hair sample was obtained to determine hair zinc concentrations. Preterm infants receiving supplemental zinc in hospital, as MNF, had significantly greater zinc retention in hospital compared to MM + CaGP but not greater hair zinc concentrations at 6 or 12 months corrected age. Despite significantly lower zinc intakes to 6 months corrected age, Post-MM had significantly greater hair zinc concentrations at 6 months compared to PTF (median[25-75th percentile]: 146[106-190] versus 85[54-91] microg/g, P < 0.05). Hair zinc in Post-FF (124[77-163] microg/g) was lower than Post-MM, but this was not significant (P = 0.09). Only in Post-MM were hair zinc concentrations above the median of reference values from term born infants at 12 months corrected age. Mean values of weight, length and head circumference of the preterm infants in Post-MM, Post-FF and PTF groups were between the 3rd and 97th percentiles derived from WHO reference growth standards for mother's milk-fed term infants. Our findings suggest that supplemental zinc either in hospital or post-hospital discharge does not appear to be required for preterm infants fed their mother's milk.

Background: Dexamethasone treatment facilitates the weaning of premature infants from mechanical ventilation but impairs protein homeostasis, lean tissue deposition, and growth. The current study was conducted to investigate whether dexamethasone mediates these effects by reducing protein synthesis or elevating protein breakdown, and whether adjuvant growth hormone ± insulin-like growth factor-I therapy can attenuate such effects. Methods: Piglets (n = 24) were randomized to placebo, a tapered course of dexamethasone (0.5, 0.3. 0.2 mg/kg per day for 5. 5 and 4 days each, respectively), dexamethasone + growth hormone 0.1 mg/kg per day, or dexamethasone + growth hormone + insulin-like growth factor-I 0.1 mg/kg per day for 14 days. On day 13, 15 N-glycine was administered as a single oral dose, and urine was collected at timed intervals during the subsequent 48 hours. Results: Total urinary N and cumulative 15 N excretion were higher in all dexamethasone groups than in control subjects. Protein synthesis was suppressed, whereas protein breakdown was unaltered by dexamethasone. Adjunctive growth hormone ± insulin-like growth factor-I therapy enhanced protein synthesis, but only combined therapy improved net protein gain compared with dexamethasone alone. Higher circulating insulin-like growth factor-I may have mediated the greater net protein gain. Blood urea nitrogen was elevated in all dexamethasone-treated groups at days 6 and I 1 but was normalized by day 15 with adjunctive growth hormone ± insulin-like growth factor-I. From a functional perspective, both adjunctive growth hormone and growth hormone ± insulin-like growth factor-I partially attenuated the dexamethasone-induced reduction in weight and length gain but not in whole body lean and fat mass. Conclusion: Adjunctive growth hormone ± insulin-like growth factor-I therapy partially reverses the dexamethasone-induced reduction in protein synthesis, resulting in improved growth when given concurrently with a low tapering dose of dexamethasone.

The purpose of this study was to investigate whether a dietary calcium:iron ratio similar to that often consumed by premature human infants inhibits iron absorption in infant piglets adapted to a high calcium diet. Male Yorkshire piglets were randomized at 3 to 4 d of age to a high calcium diet (4.67 g/L = HC) or a normal calcium diet (2.0 g/L = NC) and fed for 2 to 2.5 wk. An iron dextran injection was administered in amounts to achieve a marginal state of iron repletion to simulate iron status of premature infants. In vivo iron absorption from the diet was determined using the radiotracers 55 Fe and 59 Fe and whole body counting. Calcium:iron interactions at absorption sites in piglets fed HC and NC were investigated by measurements of time-dependent 59 Fe uptake in response to different calcium:iron ratios in vitro in brush border membrane vesicles (BBMV). In vivo iron absorption from the diet did not differ between NC and HC diet groups [57 ± 8% versus 55 ± 17% (mean ± SD), respectively]. Iron status and iron contencentrations in spleen, liver, intestine, kidney and heart did not differ between diet groups. Iron uptake in BBMV was significantly reduced by calcium in both HC and NC (P < 0.001); but there were no significant differences in iron uptake in response to different calcium:iron ratios between HC and NC. With feeding a HC diet for 2 wk there may be an adaptive response to counteract the inhibitory effects of calcium on iron absorption, thus resulting in similar in vivo iron absorption and iron status irrespective of the 1.3-fold difference in dietary calcium:iron ratio between piglet groups. However, future studies are needed to determine the specific sites of calcium:iron interactions and adaptation mechanisms. Since the calcium:iron ratios used in this study reflect the usual calcium:iron ratios in diets for premature infants, it is unlikely that interactive effects of calcium with iron will compromise iron status in this infant population when diets are supplemented with calcium.

Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone.

Previously, we conducted dual energy x-ray absorptiometry (DXA) (Hologic QDR-1000/W) scans and carcass analysis of piglets to evaluate the Pediatric Whole Body software (PedWB) (V5.35) for use in infants. A software upgrade designed for infant whole body (InfWB) (V5.56) led to a reassessment of DXA by: 1) reanalysis of the original scans using InfWB software and 2) comparison of InfWB-estimates of bone mineral content (BMC) and lean and fat mass with chemical analysis. Other assessments included 1) methods of regional analysis and 2) artifacts and the Infant Table Pad in the scan field. The mean coefficients of variation for InfWB whole body measures in small piglets (n = 10, weight 1575 +/- 73 g) and large piglets (n = 10, weight 5894 +/- 208 g) were less than 2.6% except for fat mass which was higher (8.0% versus 6.3% and 6.6% versus 3.5%, respectively) compared with PedWB. In large piglets InfWB produced good estimates of BMC, lean and fat masses. In small piglets, fat mass by InfWB was correlated with chemical analysis, but not by PedWB. There was improvement in the estimation of BMC with InfWB, from 27 +/- 2.2 g to 32 +/- 2.3 g (carcass ash = 38 +/- 3.3 g). Femur BMC analysis by InfWB was precise and was accurate when compared with chemical analysis. Artifacts in the DXA scan field (diapers and blankets) resulted in an increase of the DXA-estimated fat and lean masses. The Infant Table Pad increased the estimate of fat mass in a small piglet by 50%, thus further study is required before it is used routinely. Improvements of the DXA technology have resulted in a more accurate tool, if scanning procedures are carefully implemented.

The objective of this study in premature infants was to assess the relationship between dexamethasone, growth and bone mineral accretion. Nine appropriate size for gestational age premature infants treated for chronic lung disease with tapering doses of dexamethasone (0.5-0.1 mg/kg/day over 37 +/- 7 days) were individually matched to a comparison infant by sex, gestational age, birth-weight, and type of feed. Infant growth and bone mineral accretion were measured at equivalent gestational ages from recruitment until 6 months corrected age. During hospitalization, mean rate of weight, length and head circumference growth and bone mineral accretion in the distal radius were significantly lower in the dexamethasone-treated infants in spite of similar nutrient intakes. Dexamethasone infants had significantly lower plasma phosphorus, and urinary calcium, pyridinoline and N-telopeptide excretion. Dexamethasone affected absolute length, but not weight, throughout the study. No significant differences were observed in body composition or absolute radial and whole body bone mineral content. The results indicate that dexamethasone therapy compromises growth and bone mineral accretion in small premature infants. 'Catch-up' linear growth was not evident at 6 months of age and reflects the importance of early nutrition interventions.

The objective of this study was to assess the effect of dexamethasone on growth, body composition and protein metabolism using the piglet as a model for rapidly growing premature infants. Seven-day-old male pigs (n = 18) were randomized to 0.5 mg/kg/day oral dexamethasone or placebo for 15 consecutive days. Weight and length gains and weight gained per energy or protein consumed were significantly lower in the dexamethasone group. Serum urea nitrogen was significantly higher in the dexamethasone group by day 15 of the study. No differences were observed between groups for urinary creatinine. The whole body percent lean mass was significantly lower and percent fat mass was significantly higher in the dexamethasone piglets, as measured by dual energy X-ray absorptiometry. In young piglets, dexamethasone, at doses similar to those in premature infants, induces protein catabolism, impairs growth and alters its composition.

Children with acute lymphoblastic leukemia (ALL) often develop bone pain, abnormal gait, and unusual fractures while in remission and receiving continuing chemotherapy. A prospective longitudinal cohort study was undertaken of bone mass and biochemical mineral status in 40 consecutive children (27 male, 13 female, aged 0.3-17.0 years) receiving therapy on the Dana-Farber Cancer Institute protocol 87-01. Radiography, lumbar spine dual-photon absorptiometry, and biochemical measurements of mineral status were performed at diagnosis and at 6-month intervals throughout 24 months of chemotherapy. Eleven patients were not completely evaluated (4 deaths and 7 off study). Radiographic evidence of osteopenia was observed in 10, 64, and 76% at diagnosis, 12 and 24 months, respectively. Fractures occurred in 39% of children during treatment. Reduction in bone mineral content (BMC), as measured by Z scores, occurred in 64% of patients and was most severe in those greater than 11 years of age at diagnosis. Reduction in BMC during the first 6 months of therapy had a positive predictive value of 64%, while an increase in BMC had a negative predictive value of 82% for subsequent fracture. By 6 months of therapy, 31/37 (84%) children were hypomagnesemic, of whom 16 (52%) were hypermagnesuric. Plasma osteocalcin was subnormal at diagnosis in 29/40 (73%) but increased to normal by 6 months of treatment. Vitamin D status was normal throughout, but plasma 1,25-dihydroxyvitamin D remained subnormal in greater than 70% of children. Urinary cross-link N-telopeptide was normal at diagnosis and became elevated in 58% of children by the end of therapy. Suppressed bone mineralization is evident at diagnosis in a minority of children with ALL. Skeletal morbidity and a reduction in bone mineral mass become more prevalent during treatment, with increased bone resorption, perhaps mainly as a consequence of corticosteroid administration.

Children with acute lymphoblastic leukemia (ALL) experience fractures on the basis of osteopenia related to chemotherapy administered for the maintenance of remission. It is likely that corticosteroids are the main cause of bone mineral loss in this circumstance. Because fluoride has been used as a therapeutic intervention in osteoporosis, including that induced by corticosteroid therapy, we explored the prospect that children with ALL who received fluoride supplementation (in drinking water or from other sources) may be relatively protected from iatrogenic skeletal morbidity. Children who completed therapy according to the Dana Farber Cancer Institute protocol 87-01 (n=35) were assessed by skeletal radiology and bone densitometry every 6 months from diagnosis. In addition, their families completed a questionnaire relating to fluoride supplementation. There was no correlation between such fluoride supplementation and either the prevalence of fractures or the severity of osteopenia. This outcome may reflect the mainly appendicular location of the fractures in this group of children. These findings, together with a consideration of the risk benefit ratio of fluoride administration to children at large, suggest that such intervention is unlikely to be beneficial in limiting skeletal morbidity during the treatment of ALL in childhood.

Purpose : The purpose of this study is to assess the effects of amikacin on renal proximal tubular function, and on magnesium (Mg) and calcium (Ca) status in children treated for acute lymphoblastic leukemia (ALL). Patients and Methods : Eighteen children (11 male/7 female, ages 2-18 years) receiving antileukemic therapy (Dana Farber Cancer Institute protocols 87-001 or 91-001) and admitted for febrile neutropenia to The Children's Hospital at Chedoke-Mc-Master, Hamilton, Ontario were recruited into this descriptive prospective study. Each child was treated with amikacin (7.5 mg/kg/12 hx10-14 days) for one or more courses. Results : No patient demonstrated elevations in amikacin trough levels. β 2 -Microglobulinuria, glucosuria, proteinuria, and hyperphosphaturia were absent. Children (50%) presenting with hypomagnesemia (

OBJECTIVE To determine the feasibility of a randomized double-blind controlled trial of an infant formula without intact cow's-milk protein for preventing type I diabetes in high-risk children. RESEARCH DESIGN AND METHODS We surveyed 83 people who either were parents of a child with type I diabetes or were pregnant women with type I diabetes in the ambulatory diabetes and obstetrics clinics in a university hospital. After a written and verbal description of the cow's milk-diabetes hypothesis, participants were asked to sign a sham consent form. A questionnaire designed to explore factors affecting their decision to either sign or not sign the consent form, as well as infant-feeding patterns, was subsequently administered. RESULTS Overall, 69.9% (95% confidence interval, 60.0–79.8%) consented to participation in the proposed randomized trial. The decision to consent was not affected by the degree of belief in the cow's milk-diabetes hypothesis, the child's risk of diabetes, the respondent's demographic data, or infant feeding habits. CONCLUSIONS A randomized feeding intervention study is an acceptable and feasible way to determine whether avoidance of cow's-milk protein during the first 6 months of life prevents type I diabetes in North American children.

During endurance exercise at approximately 65% maximal O2 consumption, women oxidize more lipids, and therefore decrease carbohydrate and protein oxidation, compared with men (L.J. Tarnopolsky, M.A. Tarnopolsky, S.A. Atkinson, and J.D. MacDougall. J. Appl. Physiol. 68: 302–308, 1990; S.M. Phillips, S.A. Atkinson, M.A. Tarnopolsky, and J.D. MacDougall. J. Appl. Physiol. 75: 2134–2141, 1993). The main purpose of this study was to examine the ability of similarly trained male (n = 7) and female (n = 8) endurance athletes to increase muscle glycogen concentrations in response to an increase in dietary carbohydrate from 55–60 to 75% of energy intake for a period of 4 days (carbohydrate loading). In addition, we sought to examine whether gender differences existed in metabolism during submaximal endurance cycling at 75% peak O2 consumption (VO2 peak) for 60 min. The men increased muscle glycogen concentration by 41% in response to the dietary manipulation and had a corresponding increase in performance time during an 85% VO2 peak trial (45%), whereas the women did not increase glycogen concentration (0%) or performance time (5%). The women oxidized significantly more lipid and less carbohydrate and protein compared with the men during exercise at 75% VO2-peak. We conclude that women did not increase muscle glycogen in response to the 4-day regimen of carbohydrate loading described. In addition, these data support previous observations of greater lipid and lower carbohydrate and protein oxidation by women vs. men during submaximal endurance exercise.

Objective: To determine whether the osteopenia and unusual fractures observed in children with acute lymphoblastic leukemia (ALL) were related to the disease rather than to its treatment. Design: Prospective analysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. Methods: Biochemical indicators of mineral, endocrine, and vitamin D status were measured before initiation of therapy. Bone mass was determined radiographically and by dual-photon absorptiometry of the lumbar region of the spine (L2-L4). Correlations between clinical observations, leukemia variables, bone mass, and biochemical assessment were determined. Results: At the time of diagnosis musculoskeletal pain was present in 36% of patients and was more common in children with CD10-positive leukemia and leukocyte counts less than 20 × 109 cells/L. Radiographic evidence of osteopenia and fractures was observed in 13% and 10% of children, respectively. The mean bone mineral content was normal. Bone mass measurement z scores correlated with plasma 1,25-dihydroxyvitamin D3 concentrations (r = 0.43, p

Precision and validity of dual-energy x-ray absorptiometry (DXA) for analysis of whole-body composition in infants were assessed by 1) scanning piglets in triplicate to calculate CVs, and 2) comparing DXA estimates with chemical analysis of whole carcass. The mean CVs for all DXA measures in small piglets and large piglets were < 2.5%, except for fat mass, which were 6.3% and 3.5%, respectively. In large piglets DXA provided reasonable estimates of chemical analysis for bone mineral content (BMC), lean body mass, and fat mass, but only for lean body mass in small piglets. DXA overestimated fat by twofold and underestimated BMC by a third in small piglets. Scans of prematurely born infants (n = 17) at term and at 3, 6, and 12 mo corrected age demonstrated that changes in BMC, lean body mass, and fat mass can be quantitated by DXA. However, further refinement of DXA technology is necessary before reliable measures of BMC and fat mass in small infants are attainable.

The current Canadian Recommended Nutrient Intake (RNI) for protein (0.86 g.kg-1.day-1) makes no allowance for an effect of habitual physical activity. In addition, Tarnopolsky et al. (J. Appl. Physiol. 68: 302–308, 1990) showed that males may catabolize more protein than females consequent to endurance exercise. We examined nitrogen (N) balance and leucine kinetics during submaximal endurance exercise to determine the adequacy of the current Canadian RNI for protein for male and female endurance athletes. Athletes were matched for equal training volume, competitive status, and conditioning and were fed diets isoenergetic with their habitual intake, containing protein at the Canadian RNI. Subjects were adapted to the diet for 10 days before completing a 3-day measurement of N balance. N balance showed that the RNI was inadequate for females (-15.9 +/- 6.0 mg.kg-1.day-1) and males (-26.3 +/- 11.0 mg.kg-1.day-1). Leucine kinetics during exercise were determined for each subject on day 3 of the N balance experiment by use of a primed continuous infusion of L-[1–13C]leucine and the reciprocal pool model. Exercise resulted in a significant (P < 0.01) increase in leucine oxidation for both groups. Males oxidized a greater amount of leucine during the infusion than females (P < 0.01). Leucine flux also increased significantly (P < 0.01) during exercise in both groups. We conclude that the current Canadian RNI for protein is inadequate for those who chronically engage in endurance exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

In children with inflammatory bowel disease, controversy continues about the use of long-term alternate day prednisone therapy (ADP) to suppress disease activity and to encourage appetite and growth. One possible side effect of both disease process and prednisone therapy is risk of development of osteoporosis. To evaluate this risk factor, growth, biochemical indices of mineral and vitamin D status, and bone mass were measured in nine adolescents with Crohn's disease (CD) who were treated with ADP (0.3 mg/kg > 3 months per year) compared with eight adolescents treated with minimal ADP exposure (< 3 months per year). Single photon densitometry was used to measure bone mineral mass at the 1/3 distal radius three times over 2 years. Mean age of the 17 CD boys was 13.9 +/- 2.1 years at baseline. CD patients had lower bone BMC/BW mineral content/bone width (BMC/BW) compared with age- and height-matched normal boys at all times. The difference was less when compared to height-matched normal values as CD patients were shorter than healthy reference boys. Plasma 1,25-dihydroxyvitamin D, alkaline phosphatase, and parathyroid hormone significantly increased with treatment of disease but there were no differences between treatment groups. CD patients treated with ADP had similar heights and weights at baseline and demonstrated similar linear growth over 2 years (9.1 cm/2 years) to CD patients without ADP (10.3 cm/2 years). In both groups, BMC/BW increased significantly from year 1 to year 2, but absolute values for bone mass did not differ between the groups.

True fractional absorption of minerals was measured to determine the bioavailability of Zn, Fe, Mn and Se from liquid formulas fortified with stepwise additions of Ca and P (as Ca glycerophosphate and carbonate, Ca*P), and Zn, Cu and Fe (as sulfate salts). Growth, deposition of tracers in organs and bone mineral content of femurs as assessed by single photon absorptiometry were measured. Four-day-old piglets (n = 36) were randomly assigned to groups fed a basal diet or additions of Ca*P (Ca = 25, P = 18 g/kg dry diet), Ca*P+Zn (Zn = 0.04 g/kg), Ca*P+Zn+Cu (Cu = 0.007 g/kg) or Ca*P+Zn+Cu+Fe (Fe = 0.008 g/kg). Oral and intravenous administration of extrinsic isotopes of 59Fe, 54Mn, 65Zn, 75Se and 47Ca was followed by fecal monitoring for 15 d and true absorption calculated after accounting for endogenous excretion. Addition of Ca*P+Zn reduced Zn absorption (P < 0.05) and Ca*P+Zn+Cu reduced Fe absorption (P < 0.01), but Mn and Se absorptions were not altered. Uptake of only Zn tracer into heart was significantly different (P < 0.05) among diet groups. Weight gain and linear growth were similar in all groups. Addition of Ca*P produced higher bone mineral density, but its effect on Zn absorption warrants further investigation.

The influence of nutrient intake on body composition in growing low birthweight infants is essential knowledge in order to optimize nutritional management for the support of growth and development. Until recently, indirect methods of measuring body composition were inappropriate; but the latest generation of whole body densitometers, dual-energy X-ray absorptiometry (DXA) may be a useful tool for this age group. The application of DXA for quantitative assessment of fat, lean and bone mass should provide measures with precision and accuracy while being safe and noninvasive for use in infants and small children. Our objective was to establish the precision and accuracy of DXA measurements of whole body bone mineral content (BMC), fat and lean tissue in young piglets which are similar in body composition to infants1,2.

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.

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.

Osteogenesis Imperfecta (OI) is a brittle bone disease caused mainly by mutations in the genes coding for Type I collagen. OI is characterized by bone fragility and deformity. BrtlIV is a knock in murine model for Classical OI, carrying a Gly349Cys substitution in the alpha1(I) chain. We evaluated an in utero cell therapy treatment for OI using the murine model BrtlIV. The bone marrow cells isolated from eGFP mice were injected into E14.5 embryos and mice were analyzed at 2 m. The engraftment, detected in various organs by microscopy, was quantified in bone by confocal microscopy and in different tissues by FACS and by Real Time PCR. Analysis of type I collagen extracted from bone revealed a reduction of the mutant collagen in treated mice, indicating that donor cells, differentiated to osteoblast/osteocytes, synthesized up to 20% of all type I collagen in bone. Raman spectroscopy revealed a significant reduction of heterogeneity in mineralization around donor cells in bone. PQCT showed a statistical increase in trabecular and cortical density in long bone epiphysis of Brtl treated animals and micro CT analysis of midshaft femur detected improvement in both geometric parameters and mechanical properties. Based on our in utero treatment the stem cell transplantation seems promising to cure the disease. Supported by: Fondazione Cariplo 2007; MIUR 2006050235 and Progetto Regione Lombardia 2007 to A.F.

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.

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.

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.