Abstract: In isotope tracer experiments used in nutritional studies, it is frequently desirable both to determine the (15)N/(14)N ratios of target compounds and to quantify these compounds. This report shows how this can be achieved in a single chromatographic run for protein amino acids using an isotope ratio mass spectrometer.
Abstract: Since exclusively breast-suckled infants obtain their nutrient only from their mother's milk, it might be anticipated that a correlation will exist between the (15)N/(14)N isotope ratios of amino acids of protein of young infants and those supplied by their mother. The work presented here aimed to determine whether amino nitrogen transfer from human milk to infant hair protein synthesized within the first month of life conserves the maternal isotopic signature or whether post-ingestion fractionation dominates the nitrogen isotope spectrum. The study was conducted at 1 month post-birth on 100 mother-infant pairs. Isotope ratios (15)N/(14)N and (13)C/(12)C were measured using isotope ratio measurement by Mass Spectrometry (irm-MS) for whole maternal milk, and infant hair and (15)N/(14)N ratios were also measured by GC-irm-MS for the N-pivaloyl-O-isopropyl esters of amino acids obtained from the hydrolysis of milk and hair proteins. The δ(15)N and δ(13)C (‰) were found to be significantly higher in infant hair than in breast milk (δ(15)N, P < 0.001; δ(13)C, P < 0.001). Furthermore, the δ(15)N (‰) of individual amino acids in infant hair was also significantly higher than that in maternal milk (P < 0.001). By calculation, the observed shift in isotope ratio was shown not to be accounted for by the amino acid composition of hair and milk proteins, indicating that it is not simply due to differences in the composition in the proteins present. Rather, it would appear that each pool-mother and infant-turns over independently, and that fractionation in infant N-metabolism even in the first month of life dominates over the nutrient N-content.
Abstract: Kikuchi-Fujimoto disease is a mild and rare idiopathic disease, particularly in children. It is mostly characterized by painful cervical lymphadenopathy and/or prolonged fever and confirmed by histology. We report a case of Kikuchi-Fujimoto disease in a 14-year-old teenager with high procalcitonin concentration and thrombocytopenic purpura.
Abstract: Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease.
Abstract: Processed baby foods designed for infants (4-12 months) and toddlers (12-36 months) (excluding infant formula, follow-on formula, the so-called growing-up milks, and cereal-based foods for infants), which are referred to as baby foods, are specific products defined by a European regulation (Directive 2006/125/CE). According to this Directive, such foods have a composition adapted to the nutritional needs of children of this age and should comply with specifications related to food safety in terms of ingredients, production processes, and prevention of infectious and toxicological hazards. Hence, they differ from ordinary foods and from non-specific processed foods. This market segment includes the full range of foods that can be part of children's diet: dairy products (dairy desserts, yoghurts, and fresh cheese), sweet products (nondairy desserts, fruit, and drinks), and salty products (soups, vegetable-based foods, meat, fish, and full dishes). This market amounted to 89,666 MT in France in 2011 and 83,055 MT in 2010 (a total of 325,524 MT in the 27 countries of the European Union in 2010, including 90,438 MT in Germany, 49,144 MT in Spain, and 40,438 MT in Italy). The consumption of baby foods in France varies with infant age and parental choice. Baby foods account for 7 % of total energy intake at 4-5 months, 28 % at 6-7 months, 27 % at 8-11 months, 17 % at 1-17 months, and 11 % at 18-24 months. Among parents, 24 % never offer their children any baby foods, 13 % do so 1-3 days/week and 63 % 4-7 days/week. Among consumers, 55 % of children eat more than 250 g/day of baby foods. As baby foods only account for a minor fraction of overall food intake, their impact on the quality of young children's diet is much less than that of growing-up milks, particularly for preventing insufficient iron and vitamin D intake. Their consumption, however, has an indirect benefit on the nutritional quality of the diet and on food safety, particularly regarding toxicological hazards, as it postpones the introduction of non-specific processed foods, which are inadequate for this age group owing to both their nutritional composition and lower food safety control. Baby foods represent a family of products meeting parents' expectations and adapted to infants and young children. They are clearly beneficial in terms of food safety, but the nutritional benefit to be expected from their consumption is minimal: their main advantage is postponing or decreasing the consumption of non-specific industrially processed foods.
Abstract: Early eating patterns and behaviors can determine later eating habits and food preferences and they have been related to the development of childhood overweight and obesity. We aimed to identify patterns of feeding in the first year of life and to examine their associations with family characteristics.
Abstract: The wide variety of infant formula available on the market can be confusing for parents and physicians. We aimed to determine associations between predominant type of formula used from birth to 4 months and parental and child characteristics and type of physician consulted, and then to describe relations between type of formula used and growth. Our analyses included 1349 infants from the EDEN mother-child cohort. Infant's feeding mode and type of formula used were assessed at 4 months by maternal self-report. Infant's weight and height from birth to 4 months, measured in routine follow-up, were documented by health professionals in the infant's personal health record. Anthropometric z-scores were calculated by using World Health Organization growth standards. Multinomial logistic regression was used to identify factors associated with the type of formula predominantly used; relations with growth were analysed by linear regressions. Partially hydrolysed formulas were more likely to be used by primiparous women (P < 0.001), those breastfeeding longer (P < 0.001) and for infants with family history of allergies (P = 0.002). Thickened formulas were more often used by mothers returning to employment in the first 4 months (P = 0.05) and breastfeeding shortly (P < 0.001). No significant relation was found between infant's growth and type of formula (P > 0.20). Infants breastfed shorter showed higher weight-for-age (P < 0.001) and length-for-age (P = 0.001) z-score changes between birth and 4 months. The use of a specific type of infant formula seems to be mainly related to parental characteristics. Infant's growth in the first 4 months is related to other factors than to the type of formula used.
Abstract: Protein intake in fetal life or infancy may play a key role in determining early growth rate, a determinant of later health and disease. Previous work has indicated that hair isotopic composition is influenced by diet and protein intake.
Abstract: Children of mothers who experience depression in pregnancy may be at high risk of emotional disturbances; however heterogeneity in risk suggests that other factors could play a moderating role. We test the hypothesis that children growing up in families characterised by both maternal depression and socioeconomic disadvantage are especially likely to have temperamental difficulties.
Abstract: The diagnosis of cows' milk protein allergy (CMPA) requires first the suspicion of diagnosis based on symptoms described in the medical history, and, second, the elimination of cows' milk proteins (CMP) from the infant's diet. Without such rigorous analysis, the elimination of CMP is unjustified, and sometimes harmful. The elimination diet should be strictly followed, at least until 9-12 months of age. If the child is not breast fed or the mother cannot or no longer wishes to breast feed, the first choice is an extensively hydrolysed formula (eHF) of CMP, the efficacy of which has been demonstrated by scientifically sound studies. If it is not tolerated, an amino acid-based formula is warranted. A rice protein-based eHF can be an alternative to a CMP-based eHF. Soya protein-based infant formulae are also a suitable alternative for infants >6 months, after establishing tolerance to soya protein by clinical challenge. CMPA usually resolves during the first 2-3 years. However, the age of recovery varies depending on the child and the type of CMPA, especially whether it is IgE-mediated or not, with the former being more persistent. Once the child reaches the age of 9-12 months, an oral food challenge is carried out in the hospital ward to assess the development of tolerance and, if possible, to allow for the continued reintroduction of CMP at home. Some children with CMPA will tolerate only a limited daily amount of CMP. The current therapeutic options are designed to accelerate the acquisition of tolerance thereof, which seems to be facilitated by repeated exposure to CMP.
Abstract: Protein energy malnutrition (PEM) occurs when energy and protein intake do not meet requirements. It has a functional and structural impact and increases both morbidity and mortality of a given disease. The Nutrition Committee of the French Pediatric Society recommends weighing and measuring any child when hospitalized or seen in consultation. The body mass index (BMI) must be calculated and analyzed according to references any time growth kinetics cannot be analyzed. Any child with a BMI below the third centile or -2 standard deviations for age and sex needs to be examined looking for clinical signs of malnutrition and signs orienting toward an etiology and requires having his BMI and height dynamics plotted on a chart. PEM warrants drawing up a nutritional strategy along with the overall care plan. A target weight needs to be determined as well as the quantitative and qualitative nutritional care including its implementation. This plan must be evaluated afterwards in order to adapt the nutritional therapy.
Abstract: The aims of the present position paper by the Committee on Nutrition of the French Society of Paediatrics were to summarize the recently published data on vitamin D in infants, children and adolescents, i.e., on metabolism, physiological effects, and requirements and to make recommendations on supplementation after careful review of the evidence. Scientific evidence indicates that calcium and vitamin D play key roles in bone health. The current evidence, limited to observational studies, however, does not support other benefits for vitamin D. More targeted research should continue, especially interventional studies. In the absence of any underlying risk of vitamin D deficiency, the recommendations are as follows: pregnant women: a single dose of 80,000 to 100,000 IU at the beginning of the 7th month of pregnancy; breastfed infants: 1000 to 1200 IU/day; children less than 18 months of age, receiving milk supplemented with vitamin D: an additional daily dose of 600 to 800 IU; children less than 18 months of age receiving milk not supplemented with vitamin D: daily dose of 1000 to 1200 IU; children from 18 months to 5 years of age: 2 doses of 80,000 to 100,000 IU every winter (November and February). In the presence of an underlying risk of vitamin D deficiency (dark skin; lack of exposure of the skin to ultraviolet B [UVB] radiation from sunshine in summer; skin disease responsible for decreased exposure of the skin to UVB radiation from sunshine in summer; wearing skin-covering clothes in summer; intestinal malabsorption or maldigestion; cholestasis; renal insufficiency; nephrotic syndrome; drugs [rifampicin; antiepileptic treatment: phenobarbital, phenytoin]; obesity; vegan diet), it may be justified to start vitamin D supplementation in winter in children 5 to 10 years of age as well as to maintain supplementation of vitamin D every 3 months all year long in children 1 to 10 years of age and in adolescents. In some pathological conditions, doses of vitamin D can be increased. If necessary, the determination of 25(OH) vitamin D serum concentration will help determine the level of vitamin D supplementation.
Abstract: Assessing the nutritional status is like the bottom line of children's health. The first step is to measure height and weight in proper conditions and to calculate the body mass index (BMI). BMI for sex and age allows identifying overweight and obese as well as underweight children. Both situations lead to a clinical exam in order to find causative disease (obesity of endocrine or genetic origin, malnutrition from somatic or behavioral disease). Routine lab study might help whenever referral to specialist is necessary. Nutritional anemia and vitamin D deficiency are two common situations in children that have to be screened and treated. The general practitioner has a central role in nutritional problems in children since he can manage the care within the whole family. This is particularly the case for obesity but also for dyslipidemia, that has to be screened around 8 years, both being major familial risk factor for cardiovascular diseases.
Abstract: New data on food allergy has recently changed the management of children with cow's milk protein allergy (CMPA). The diagnosis of CMPA first requires the elimination of cow's milk proteins and then an oral provocation test following a standard diagnostic procedure for food allergy, without which the elimination diet is unjustified and sometimes harmful. Once the diagnosis is made, the elimination diet is strict, at least until the age of 9-12 months. If the child is not breastfed or the mother cannot or no longer wishes to breastfeed, the first choice is a formula based on extensive hydrolyzate of cow's milk (eHF), provided that its effectiveness has been demonstrated. When eHF fails, a formula based on amino acids is warranted. eHF based on rice protein hydrolysates is an alternative to cow's milk eHF. Infant formulas based on soy protein can be used after the age of 6 months, after verification of good clinical tolerance to soy. Most commonly, CMPA disappears within 2 or 3 years of life. However, the age of recovery varies depending on the child and the type of CMPA, and whether or not it is IgE-mediated, the first being more sustainable. When the child grows, a hospital oral provocation test evaluates the development of tolerance and, if possible, authorizes continuing the reintroduction of milk proteins at home. Some children with CMPA will tolerate only a limited daily amount of cow's milk proteins. The current therapeutic options are designed to accelerate the acquisition of tolerance, which seems facilitated by regular exposure to cow's milk proteins.
Abstract: The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln) supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.
Abstract: To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately.
Abstract: The occurence of mutism after thalamic lesions has rarely been observed before adulthood. We report a 6.5-year-old girl who presented with sudden mutism with a decreased level of alertness. Her MRI revealed a T2-fluid attenuated inversion recovery hyperintensity in both thalami, which suggested bithalamic infarction in the territory of the thalamo-perforating arteries and, more specifically, the para-median territories. Mutism was followed by a deficit of speech initiation with slow and slurred speech. Her speech returned to normal at 3 months after the onset of symptoms. Thus mutism could be the equivalent of akinetic mutism limited to the speech sphere.
Abstract: To compare the ability of bioelectrical impedance analysis (BIA) and skinfold thickness (ST) measurements to estimate changes in body composition in Duchenne muscular dystrophy (DMD).
Abstract: OBJECTIVE: To determine the prevalence and distribution of the various forms of juvenile idiopathic arthritis (JIA) in the Poitou-Charentes region of Western France. METHODS: We surveyed all the practicing rheumatologists and pediatricians in the study region for cases of JIA meeting ILAR criteria seen in 2006 among the population of 305,198 children younger than 16 years of age who resided in the study region. The survey was conducted by means of a questionnaire followed by a phone call. Cases of JIA identified by the survey were reviewed retrospectively. RESULTS: We identified 48 children with JIA, which yielded a prevalence of 15.7/100,000. Mean age at diagnosis was 6.6 years (range, 1-15 years). Oligoarticular disease was the most common pattern, with 20 (41.6%) patients, a mean age of 4.9 years at diagnosis, and 80% of females. Oligoarticular disease was associated with the best outcomes, and only two (2/20, 10%) patients in this subgroup required disease-modifying therapy. Enthesitis-related arthritis contributed eight (16.6%) patients, with a mean age at diagnosis of 10.7 years and 75% of males. There were nine patients with polyarticular disease and seven with systemic disease; disease severity was greatest in these 16 patients, of whom only two were not taking disease-modifying drugs or glucocorticoids. CONCLUSION: The prevalence of JIA in Poitou-Charentes was similar to the prevalences reported in other regions of France.
Abstract: BACKGROUND: Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD. METHODOLOGY/PRINCIPAL FINDINGS: 30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated. CONCLUSIONS: This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise. TRIAL REGISTRATION: (ClinicalTrials.gov) NCT00296621.
Abstract: Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease associated with increased atherosclerosis, resulting in premature death near the age of 20 years. Treatment requires the LDL-apheresis system. M, born from a consanguineous union, suffers from HFH (total-cholesterol=12.29 g/l, LDL-cholesterol=9.65 g/l). Diet and drug treatment was not associated with decreased LDL-cholesterol. At the age of 4.5 years (body weight: 16.7 kg), M began treatment with LDL-apheresis. Apheresis treatment was given every 2 weeks using the Direct Adsorption of LIpoprotein (DALI system, a process that involves total-blood filtration. During the first 26 sessions, the mean reduction in LDL-cholesterol was 67+/-12%, while HDL-cholesterol decreased by only 17+/-11%. Mean LDL-cholesterol concentration decreased from 6.54+/-0.93 g/l (before apheresis) to 2.21+/-0.95 g/l (after apheresis). Apart from iron deficiency anemia, no major side effects were observed. LDL-apheresis using the DALI system is associated with significant reductions in LDL-cholesterol (similar to reports from the literature) without major side effects, even in a child weighing less than 20 kg. A long term, multinational (European) study is needed to confirm these results.
Abstract: To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. l-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln + Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.
Abstract: OBJECTIVE: The purpose of this work was to compare breastfeeding practices, perceptions, and infant weight change of prepregnant obese versus normal-weight mothers in the first 3 months postpartum. PATIENTS AND METHODS: For the prospective case-control study, obese mothers (prepregnant BMI > or = 30 kg/m(2)) were matched with normal-weight mothers (18.5 < or = prepregnant BMI < 25 kg/m(2)) according to initial infant feeding, parity, maternal age, ethnicity, and education. Participants completed an oral questionnaire in the hospital and a telephone interview at 1 and 3 months postpartum. RESULTS: Of 1432 mothers who had given birth at a university hospital in France, 10% were obese. Breastfeeding initiation was lower for obese (48%) versus normal-weight (64%) mothers. A total of 111 of 141 obese mothers were paired with 111 normal-weight mothers. Infant birth weight was similar for newborns of obese and normal-weight mothers. Among mothers who initiated breastfeeding, infant weight gain from 0 to 1 month was lower in breastfed infants of obese mothers compared to normal-weight mothers. Obese mothers were less likely to maintain full breastfeeding at 1 month and 3 months. The percentage of mothers breastfeeding to any extent did not differ between obese and reference women. Obese mothers more often felt uncomfortable breastfeeding in public at 3 months. Fewer obese mothers perceived that their milk supply was sufficient at 1 month and 3 months. Despite greater breastfeeding difficulties, obese mothers were less likely to seek support for breastfeeding in the first 3 months postpartum. CONCLUSIONS: Pediatricians and health professionals should recognize that obese mothers have different breastfeeding practices and perceptions. Extra support and intervention are needed among obese mothers during prenatal and early postnatal periods so that their children can benefit from breastfeeding.
Abstract: OBJECTIVE: To identify subjective factors that lead investigators not to invite eligible individuals to participate in pediatric studies. DESIGN: Qualitative study with semistructured interviews. SETTING: Four pediatric teaching hospitals in Paris. PARTICIPANTS: Pediatric investigators (n=24). MAIN OUTCOME MEASURE: Report by investigator that eligible patients were not invited by him or her to participate in a clinical research study. RESULTS: Sixty-three percent of investigators (15 of 24) reported not inviting eligible patients. The noninvitation patterns were global (ie, investigators did not invite anyone) (37.5% [9/24]) or targeted specific patient subgroups (37.5% [9/24]). Noninvitation was often described as driven by ethical concerns related to the study design or patients or by anticipated patient refusal (58.3% [14/24]). None of the investigators kept records of noninvitation rates or refusal rates. Investigators estimated refusal rates of 1% to 10%, and none remembered a study that had failed because of potential subjects' refusals (including healthy participants). CONCLUSIONS: Noninvitation to participate in studies is not an absence of action but rather is an organized practice that reflects investigators' perceptions. Consequences are practical (eg, recruitment bias and study failure) and ethical (eg, unequal access to trials and failure to respect the autonomy of eligible patients). Our data suggest an urgent need for quantitative studies aimed at documenting and understanding noninvitation of eligible patients to participate in research studies in pediatrics and in other medical specialties.
Abstract: Children with history of broncho-pulmonary dysplasia (BPD) often suffer from growth failure and lung sequelae. The main objective of this study was to test the role of pulmonary obstruction on resting energy expenditure (REE) and nutritional status in BPD. Seventy-one children with BPD (34 boys and 37 girls) and 30 controls (20 boys and 10 girls) aged 4-8 years were enrolled. Body composition was assessed by bio-impedancemetry measurements; REE was measured by indirect calorimetry. Predicted REE was calculated using the Schofield equation. The population of children with BPD was divided into three groups: children without obstruction of the airways, children with moderate obstruction of the airways, and children with severe obstruction. Children with BPD were significantly smaller and leaner than controls. Altered body composition (reduction of fat mass) was observed in BPD children that suffered from airway obstruction. REE was significantly lower in children with BPD compared to controls, but when adjusted for weight and fat-free mass no significant difference was observed irrespective of pulmonary status. Airway obstruction in children with BPD does not appear to be associated with an increased REE. Moreover altered REE could not explain the altered nutritional status that is still observed in BPD in later childhood. This supports the hypothesis that body composition and pulmonary function in BPD in later childhood are fixed sequelae originating from the neonatal period.
Abstract: BACKGROUND: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD). OBJECTIVE: To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture. DESIGN: Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous, nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before and 10 d after supplementation. RESULTS: A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1) . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4 micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol . kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups. CONCLUSION: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.
Abstract: Since children with bronchopulmonary dysplasia often suffer from malnutrition and growth failure, evaluation of body composition is a very important tool to nutritional support. The aim of this study was to compare assessment of fat-mass (FM) and fat-free mass (FFM), evaluated by bio-impedancemetry and anthropometry compared to dual-X-ray-absorptiometry (DXA) in children with bronchopulmonary dysplasia. PATIENTS: Seventy-one children, aged 4-8 years, with bronchopulmonary dysplasia were enrolled. METHODS: FM and FFM measured using anthropometry and bio-impedancemetry were compared to FM and FFM obtained by DXA using the Bland-Altman method. RESULTS: Both bio-impedancemetry and anthropometry gave good agreement with DXA to evaluate FM and FFM. Anthropometry method, in general, slightly under-estimated FM (mean difference: -0.02 kg, standard deviation: 0.99) and FFM (mean difference: -0.70 kg+/-1.72). Bio-impedancemetry method overestimated FM (mean difference: 0.34 kg+/-2.06) and underestimated FFM (mean difference: -1.24 kg+/-3.32). CONCLUSION: In children with bronchopulmonary dysplasia aged, 4-8 years, both anthropometry and bio-impedancemetry cannot be used to precisely evaluate body composition.
Abstract: BACKGROUND: Duchenne muscular dystrophy (DMD) is often associated with obesity, which worsens the handicap early in the course of the disease. Nutritional assessment, however, can be difficult and often misleading in DMD. OBJECTIVE: Two methods of estimating body composition in DMD, skinfold-thickness (ST) measurement and bioelectrical impedance analysis (BIA), were compared with a reference method, labeled water dilution (WD). DESIGN: Body composition was estimated by using ST measurements and BIA (50 kHz, 800 mAmp), as well as the WD method (1 mL H2(18)O/kg) in 11 DMD patients with a mean (+/-SD) age of 10.0 +/- 2.5 y. RESULTS: When compared with the WD method, ST measurement significantly (P < 0.01) overestimated fat-free mass (FFM) (mean +/- SD ST: 24.5 +/- 5.9 kg; mean +/- SD WD: 18.2 +/- 2.5 kg), which led to an underestimation of the percentage of fat mass (%FM) (ST: 23.3 +/- 10.4%; WD: 40.1 +/- 17.1%; P < 0.05). In contrast, estimates obtained with BIA (FFM: 21.5 +/- 4.5 kg; %FM: 31.3 +/- 13.9%) did not differ from those obtained with WD. The difference from the reference method was less for BIA (mean: 3.3 kg; 95% CI: 0.8, 4.9 kg) than for ST (6.3 kg; 2.2, 8.6 kg). WD and BIA defined 73% and 55%, respectively, of the children as obese (%FM associated with body mass index cutoffs for obesity), whereas ST measurements defined 9% as obese (P < 0.01). CONCLUSIONS: Body-composition estimates by BIA are closer to those by WD than are those by ST measurement. Early detection of fat accumulation and longitudinal monitoring of nutritional care are 2 relevant applications of BIA to prevent obesity and hence lessen the burden of DMD.
Abstract: Chronic pulmonary infection by Pseudomonas aeruginosa is observed in 50% of patients with cystic fibrosis and requires the use of recurrent intravenous therapy. A decrease of resting energy expenditure (REE) and an increase of physical activity (PA) after intravenous anti-P. aeruginosa therapy (IVAT) is observed while total energy expenditure (TEE) does not change. A decrease in the energetic cost of physical activity (ECPA) could be hypothesized but has never been studied. Our aim was to assess the evolution of ECPA after home IVAT in both standardized condition at hospital and in free-living condition twice before and after IVAT. Sixteen CF patients (nine boys, seven girls) chronically colonized by P. aeruginosa with a mean age of 12.1+/-2.3 years (range 7.1-14.6) were studied before and after IVAT. Each patient passed throughout a visit in hospital: weight, height and fat-free mass were measured. Then, energy expenditure (EE) measured by indirect calorimetry and heart rate (HR) were simultaneously recorded at different levels of PA: REE, and at different intensity of physical activities on a cycloergometer using an incremental increase of the power brake force. Physical activity energy expenditure (PAEE) was computed in laboratory condition using PAEE=EE-BEE (basal energy expenditure). Linear regression between PAEE and power brake force was fitted for each patient before and after IVAT. ECPA in standardized conditions was compared at different range of power brake force using area under the curve (AUC). After coming back at home, 24 h TEE using the heart rate monitoring technique and PA by triaxial accelerometry were simultaneously measured in free-living condition for 24 h during a school day. ECPA in free-living conditions was compared by the ratio PAEE:PA where PAEE=DEE-REE (DEE=daily energy expenditure). After IVAT, median AUC between 60 and 90 W in standardized condition decreased significantly by -15.4% (median 14.9, range 8.8-30.3 vs. median 12.6, range 8.5-17.6; P<0.05, Wilcoxon rank test) while the decrease for lower range of power work load did not reach significance. Spearman correlation was significant between variations of forced expiratory volume in 1 s and variation of AUC at 30-60 W before and after IVAT in standardized condition. In free-living conditions, ratio PAEE/PA did not vary significantly (median 3.4, range 1.6-6.4 vs. median 2.8, range 1.4-4.8; NS). Our data demonstrate a decrease of ECPA after IVAT in standardized conditions for moderate level of PA (60-90 W), but not in free-living conditions. The decrease of ECPA was probably due to a decrease in the energetic cost of breathing after IVAT, that is particularly relevant to promote PA in CF patients.
Abstract: OBJECTIVE: To assess the rate of progression of lipodystrophy and the associated metabolic disturbances over a 2-year period in children and to assess risk factors associated with lipodystrophy and metabolic disturbances. DESIGN: Multicenter 2-year prospective study with a standardized evaluation. METHODS: One hundred thirty children (median age = 10 years, 64 boys and 66 girls) receiving antiretroviral therapy were recruited in 3 pediatric clinics. Lipodystrophy was defined based on 4 skinfold thickness measurements. Fasting lipids and glucose profile were measured in all children. RESULTS: The proportion of children presenting with lipodystrophy was 24.6%. Nineteen percent of children had high-density lipoprotein values less than 1 mmol/L. Twenty-two percent and 15% of children had values greater than 2 standard deviations for age and gender for cholesterol and triglycerides, respectively. A total of 13.2% showed insulin resistance. A total of 42.7% showed at least 1 of these biologic disturbances. Prospective follow-up showed no progression at all over 2 years, except for a doubling of the number of children with insulin resistance. In multivariate analyses, ethnicity, previous severe clinical condition, duration of HIV infection, and nucleoside reverse transcriptase inhibitor treatment were significantly associated with lipodystrophy. Tanner stage V of puberty, severe clinical symptoms and protease inhibitor treatment were independently associated with the risk of metabolic disturbances. CONCLUSIONS: Puberty seems to be the time when HIV-infected children taking potent antiretroviral therapy are more likely to develop lipodystrophy and metabolic complications, especially in children with a severe underlying HIV infection. Once developed, lipodystrophy and metabolic changes seem to be extremely stable with time.
Abstract: A prospective study was performed in a paediatric hospital to evaluate the incidence of bacterial contamination in enteral nutrition bags and to determine the critical points of process. During two separate one-month periods, all children receiving pump-assisted enteral nutrition were enrolled in the study. Samples for microbiological analysis were collected from enteral nutrition bags after administration in the first and second study period (sample T(2)). In the second study period, two additional samples were made at the end of the feed preparation process. One was refrigerated immediately (sample T(0)) and the other was sealed in a tube that followed the enteral nutrition solution until the end of its administration (sample T(1)). Bacterial contamination was detectable above 10(2)cfu/mL. Twenty-six out of 40 patients were included in the first study period and 14 out of 44 in the second study period. Contamination (>10(2)cfu/mL) occurred in nine of 26 samples (35%) and seven of 14 samples (50%) in the first and second study periods, respectively. Of these, five (20%) and three (21%) contained significant contamination (>/=10(4)cfu/mL). Bacteria of low pathogenicity were found in T(0) samples. Bacteria present in T(2) samples were pathogenic and multiple in 50% of cases. These results suggest that manipulation of the enteral nutrition bags at the bedside is critical for bacterial safety.
Abstract: Long-term glucocorticoid treatment contributes to the growth retardation in children after renal transplantation. We investigated whether determination of prednisone (PN) and prednisolone (PL) in plasma and PN, PL, and 6-beta-hydroxyprednisolone (betaOH-PL) in urine could help to predict growth. PN and PL pharmacokinetics were studied in 36 children, from 5 to 15 years of age, receiving daily (D) or alternate-day (AD) oral PN treatment. Statural growth velocity was evaluated over a 1-year period. We compared three groups of children according to the growth kinetics during the study year (catch-up, stable, or decline) for clinical and pharmacokinetic parameters. A multiple linear regression analysis was performed in order to determine pharmacokinetic parameters able to explain height 1 year after inclusion. Height at the beginning of the study, creatinine clearance, and type of D or AD treatment explained 94.2% of height variance 1 year after inclusion. Only PL clearance was associated with growth evolution, but introduction of PL clearance in the multivariate model did not improve the variance of height accounted for by the previous model. We, therefore, do not recommend using glucocorticoid pharmacokinetics to predict growth retardation in children with renal transplantation.
Abstract: Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (OCD) have generated discrepant results. Here, we genotyped the 5-HTTLPR polymorphism in 106 French OCD patients and 171 healthy controls (case control study). We also performed a family association study on 116 trios including an OCD patient (73 French and 43 German). No association was detected between the 5-HTTLPR polymorphism and OCD in either the case control study or the family study.
Abstract: Determining total energy expenditure (TEE) and its components in children treated with home parenteral nutrition (CHPN) under free-living conditions is an important consideration in the assessment of energy requirements and the maintenance of health. The aim of this study was to assess TEE and physical activity in CHPN. Eleven CHPN (three girls and eight boys; median age, 6.0 y; range, 4.5-15.0 y) were compared with 11 healthy children (three girls and eight boys; median age, 6.0 y, range, 4.5-14.0 y) after pairing for sex, age, and weight. Underlying diseases included chronic intractable diarrhea (n = 5), short bowel syndrome (n = 3), and intestinal dysmotility (n = 3). None of these children had inflammatory disease or recent infection when studied. Fat-free mass (FFM), measured by body impedance analysis, fat mass (FM), measured by skinfold thickness, and energy intake were similar between the two groups, suggesting that CHPN had normal body composition and energy intake. Resting energy expenditure (REE), measured by indirect calorimetry, and TEE, assessed by a technique using 24-h heart-rate monitoring calibrated against indirect calorimetry and physical activity using a triaxial accelerometer, were simultaneously recorded and were also similar in the two groups. Sleeping energy expenditure (SEE), expressed per kilogram of FFM, was significantly greater in the CHPN group (median, 0.15; range, 0.10-0.23 kJ/min/kg FFM versus median, 0.12; range, 0.09-0.21 kJ/min/kg FFM for controls; p < 0.05, Wilcoxon rank test). These findings were explained by the high correlation between the energy flow infused by parenteral nutrition and sleeping energy expenditure (p < 0.05, Spearman test) and also-diet induced thermogenesis (p < 0.05 Spearman test). These results suggest that the energy requirements of children on long-term home parenteral nutrition programs do not differ from controls and that cyclic parenteral nutrition does not interfere with physical activity.
Abstract: Malnutrition is a common complication of chronic diseases in children and may lead to growth impairment (stunting). Malnutrition in cystic fibrosis (CF) results from increased energy expenditure, decreased energy intakes, malabsorption of ingested nutrients because of pancreatic insufficiency and chronic inflammation. Malnutrition and high levels of inflammatory cytokines affect IGF-1 production through interrelated mechanisms. Nutritional support was shown to improve both nutritional status and outcome in CF. However, some nutrients have a direct effect on the disease. n-3 fatty acids supplementation is able to correct lipid abnormalities resulting from a primary mechanism. Moreover, n-3 fatty acids have a direct effect on the inflammatory response, decreasing eicosanoid synthesis and modulating nuclear transcriptional factors nuclear factor kappaB and peroxisome proliferator-activated receptors gamma. Nutritional support may be considered part of the care of the CF patient together with antibiotics, pancreatic enzymes and physiotherapy, influencing significantly the evolution of the disease.
Abstract: PURPOSE: Intravesical morphine was recently recommended to reduce postoperative pain after reimplantation surgery for vesicoureteral reflux in children. The efficacy of such treatment, so far solely evaluated by open study, needed to be confirmed. MATERIALS AND METHODS: After parental informed consent was obtained, 80 children requiring Cohen cross-trigonal reimplantation were considered for inclusion in a double-blind study. On the day of surgery patients were randomly assigned to receive either 0.04 mg./kg. morphine per hour or placebo (normal saline) at a constant intravesical infusion rate of 0.08 ml./kg. per hour. Postoperative pain was assessed every 3 hours using a pain score adapted to patient age. If the score was above a predefined limit, patients received intravenous acetaminophen and nalbuphine alternately every 3 hours. Bladder infusion was discontinued after 48 hours. RESULTS: Mean and maximum pain scores as well as the number of scores above the limit were not statistically different when comparing the morphine and placebo groups. There was no difference in the number of doses of analgesics administered. Urine output, voiding frequency and the number of painful voiding episodes were not significantly different between the 2 groups. Plasma morphine concentrations were 3.0 +/- 2.7 and 1.9 +/- 1.9 ng./ml. at 24 and 48 hours in the morphine group and undetectable in the placebo group. CONCLUSIONS: Intravesical administration of morphine is not effective for relieving postoperative pain during the first 48 hours after intravesical ureteral reimplantation. This study emphasizes the importance of controlled studies in evaluating the effectiveness of a new drug or procedure before recommending its use for all patients.
Abstract: BACKGROUND: Data on the proton pump inhibitor lansoprazole in paediatric patients are limited. AIM: To investigate the pharmacokinetics, optimal dosage and efficacy of lansoprazole in paediatric patients. METHODS: A 24-h gastric pH recording and a pharmacokinetic study were performed after 7 days of lansoprazole, 17 mg/m2, in 23 patients with reflux oesophagitis (median age, 3.5 years). Response was defined as pH > 3 for > 65% of the recording. The dosage was doubled in non-responders. Patients with no response on day 14 were excluded. Responders underwent endoscopy after 4 weeks on the response-inducing dosage; abnormal findings led to a repeat endoscopy after four additional weeks. RESULTS: Nine patients responded to 17 mg/m2 and six to 30.3 mg/m2. On day 7, time with pH > 3 was significantly correlated with the area under the plasma concentration-time curve (P=0.003). The area under the plasma concentration-time curve was significantly greater in the nine responders to 17 mg/m2 than in the 14 other patients. Pharmacokinetic parameters were similar in responders and non-responders to the higher dose. After 4 weeks, oesophagitis was healed in 80% of responders. Adverse events occurred in three patients and required treatment discontinuation in one. CONCLUSIONS: Lansoprazole is effective and safe in children. The optimal starting dosage is 30 mg/m2 or 1.4 mg/kg.
Abstract: BACKGROUND: A few studies report malnutrition in hospitalized patients. MATERIAL AND METHODS: This one-day cross-sectional survey performed in January 1999 assessed nutritional status and protein-energy intake in a pediatric population hospitalized in medicine or surgery units. Every child older than six months, hospitalized for more than 48 h and free of nutritional support (parenteral, enteral, or special regimens for metabolic diseases) was included. RESULTS: Fifty-eight children among the 183 present the day of the study met the inclusion criteria and were included in the statistical analysis. They were hospitalized in medicine (48%), psychiatry (31%) and surgery (21%). The body mass index (BMI) was below -2 standard deviations (DS) in 21% of them. Excluding patients with anorexia nervosa, BMI was < -2 SD, > +2 SD, or in between these limits in respectively 12, 14 and 74%. Energy intake measured at the hospital was below 75% of the recommended dietary allowances in two-thirds of the children whether malnourished or not. Fifty percent of the malnourished children had been referred to a dietician the day of the study. CONCLUSIONS: Malnutrition is frequent in a population of hospitalized children. Energy intake and referral to a dietician are insufficient.
Abstract: The aim of this study was to determine the metabolism and the tolerance of a new amino acid (AA) solution administered under conditions mimicking cyclical parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1) (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake was increased progressively for 90 min; thereafter, AA infusion was started and maintained at a constant rate for 10 h. Plasma and urine concentrations of all the AAs were measured before, during and after the PN. For each given AA, the relation between plasma variations at the steady-state and infusion rate, plasma clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during the PN period. The results are presented as means+/-sem. All plasma AA concentrations decreased during the starting period of non-protein energy intake. The plasma AA concentrations reached a steady-state within 3 h upon AA infusion, except for glycine and lysine (6 h). At the steady state, the plasma concentrations of the infused AAs were closely correlated to their infusion rate (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained during the PN, which indicates that the solution might stimulate the de novo synthesis of this AA. When the PN was stopped, plasma levels of the AAs decreased, most of them returning to their basal levels, or significantly below for lysine (P<0.05), alanine (P<0.05), proline (P<0.01) and glutamine (P<0.05). No volunteer showed any adverse effect during the infusion period. DeltaN was: 0.8+/-0.5 gN/10 h. Metabolic characteristics for essential AAs were: Cl<0.5 l min(-1), Clr <1.5 ml x min(-1) Reab >or= 99%, Reten >or=99% and for non-essential AAs: Cl <0.6 l x min(-1) except aspartate (2.8+/-0.3 l x min(-1)), Clr < 3 ml x min(-1) except glycine (6.8+/-0.7), aspartate (8.2+/-3.5) and histidine (8.8+/-1.3); Reab >or= 98% except glycine (95+/-1), aspartate (94+/-2) and histidine (94+/-1), Reten >or=97% except histidine (94+/-1), glycine (95+/-3). These results indicate that in healthy subjects, the amounts of AAs provided by the new solution were well balanced for an intravenous administration, and so were well utilized without excessive urinary excretion. The present study provides useful metabolic parameters for a further evaluation in disease.
Abstract: The aim of this study was to investigate whether insulin resistance-associated in utero undernutrition was related to changes in insulin action on gene expression of molecules involved in the insulin signaling pathway and peripheral glucose metabolism in muscle and adipose tissue. Thirteen insulin-resistant subjects born with intrauterine growth retardation (IUGR) were matched for age, gender, and body mass index to 13 controls. Gene expression of insulin receptor, insulin receptor substrate-1, p85alpha phosphatidylinositol 3-kinase, glucose transporter-4 (GLUT4), hexokinase II, and glycogen synthase was studied in skeletal muscle at baseline and after a 3-h euglycemic insulin stimulation. Target messenger ribonucleic acid (mRNA) levels were quantified using the RT-competitive PCR method. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (36.9 +/- 12, 7 vs. 53.9 +/- 12.7 micromol/kg.min; P = 0.007), affecting both the glucose oxidation rate and the nonoxidative glucose disposal rate. At baseline, the expression of the six genes in muscle did not significantly differ between the two groups. The insulin-induced changes over baseline were comparable in both groups for all mRNAs, except GLUT4. In contrast to what observed in the control group (mean increment, 49 +/- 23%; P = 0.0009), GLUT4 expression was not stimulated by insulin in the IUGR group (8 +/- 8%; P = 0.42). Moreover, the magnitude of the defect in GLUT4 mRNA regulation by insulin was correlated to the degree of insulin resistance (r = 0.73; P = 0.01). A similar lack of significant GLUT4 mRNA stimulation by insulin was observed in the adipose tissue of IUGR-born subjects. In conclusion, insulin resistance in IUGR-born subjects is associated with an impaired regulation of GLUT4 expression by insulin in muscle and adipose tissue. Our data provide additional information about the mechanism of insulin resistance associated with in utero undernutrition and strengthen the role of glucose transport in the control of insulin sensitivity.
Abstract: To determine the effect of glucose availability on glutamine metabolism, glutamine kinetics were assessed under conditions of hyperglycemia resulting from 1) intravenous infusion of 7.5% dextrose in healthy adults and 2) insulin deficiency in young adults with insulin-dependent diabetes mellitus (IDDM). Eight healthy adults and five young adults with IDDM were studied in the postabsorptive state by use of a primed continuous infusion of D-[U-(14)C]glucose, L-[5,5,5-(2)H(3)]leucine, and L-[3, 4-(13)C]glutamine. Whether resulting from insulin deficiency or dextrose infusion, the rise in plasma glucose was associated with increased glucose turnover (23.5 +/- 0.7 vs. 12.9 +/- 0.3 micromol. kg(-1). min(-1), P < 0.01 and 20.9 +/- 2.5 vs. 12.8 +/- 0.4 micromol. kg(-1). min(-1), P = 0.03, in health and IDDM, respectively). In both cases, high blood glucose failed to alter glutamine appearance rate (R(a)) into plasma [298 +/- 9 vs. 312 +/- 14 micromol. kg(-1). h(-1), not significant (NS) and 309 +/- 23 vs 296 +/- 26 micromol. kg(-1). h(-1), NS, in health and IDDM, respectively] and the estimated fraction of glutamine R(a) arising from de novo synthesis (210 +/- 7 vs. 217 +/- 10 micromol. kg(-1). h(-1), NS and 210 +/- 16 vs. 207 +/- 21 micromol. kg(-1). h(-1), NS, in health and IDDM, respectively). When compared with the euglycemic day, the apparent contribution of glucose to glutamine carbon skeleton increased when high plasma glucose resulted from intravenous dextrose infusion in healthy volunteers (10 +/- 0.8 vs. 4.8 +/- 0.3%, P < 0.01) but failed to do so when hyperglycemia resulted from insulin deficiency in IDDM. We conclude that 1) the contribution of glucose to the estimated rate of glutamine de novo synthesis does not increase when elevation of plasma glucose results from insulin deficiency, and 2) the transfer of carbon from glucose to glutamine may depend on insulin availability.
Abstract: High fat containing diets lower VCO(2)in patients with impaired pulmonary function fed at a high level of energy intake. We tested the effect of a high fat enteral nutrition on VCO(2)and substrate oxidation in cystic fibrosis patients fed enterally 130% RDA. VCO(2)and substrate oxidation were studied in a group of eight 6-19 year old patients while receiving for 1 month and in a random order isocaloric (1000 kcal/m(2)), isonitrogenous enteral diet with a normal fat and a high fat content (40% and 67% of non-protein energy intake). Substrate oxidation and net balance were estimated using indirect calorimetry at the end of each study period. Overnight high fat enteral infusion resulted in no significant change in VCO(2)and VO(2)but lowered RQ (0.84 +/- 0.01 vs 0.88 +/- 0.01, P= 0.02) and non-protein RQ (0.83 +/- 0.01 vs 0.88 +/- 0.01). In spite of a higher glucose oxidation rate (8.1 +/- 0.5 vs 6.3 +/- 0.5 g. h(-1), P= 0.04), glucose net balance was significantly higher during normal fat formula administration (+2.5 +/- 0.8 v -0.3 7plusmn; 0.7 g/h, P< 0.05). The present study failed to show any benefit of a high fat diet on VCO(2)in non oxygenodependant cystic fibrosis children and adolescents fed slightly above RAD. Normal fat enteral formula led to higher glycogen repletion.
Abstract: To determine whether whole body protein kinetics are altered in Duchenne muscular dystrophy (DMD), six 9 +/- 1-year-old children with DMD and five weight and height matched controls, received intravenous infusion of L-[1-(13)C]leucine and L-[2-(15)N]glutamine in the post-absorptive state. Glutamine rate of appearance was approximatly 24% lower in DMD boys than in controls (321 +/- 22 vs 425 +/- 37 micromol kg(-1)h(-1), P< 0.05) resulting from a 32% decrease in glutamine de novo synthesis (230 +/- 21 vs 340 +/- 34 micromol kg(-1)h(-1), P< 0.05). Whereas there was no difference between groups in estimates of protein degradation and synthesis, leucine oxidation rate was 44% higher in DMD boys than in controls (23 +/- 2 vs 16 +/- 2 micromol kg(-1)h(-1), P< 0.05). The data suggest that the dramatic mucle mass loss observed in DMD boys is associated with a) significant protein wasting, since increased leucine oxidation reflects a more negative whole body leucine balance, and b) a significant decrease in glutamine availability in the postabsorptive state. Glutamine might therefore be a 'conditionally essential' amino-acid in DMD.
Abstract: We determined whether glutamine has a protein anabolic effect in six 8-13-y-old boys with Duchenne muscular dystrophy. Children received a 5-h i.v. infusion of L-[1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state on two consecutive days while drinking: 1) flavored water on one day, and 2) the same drink mixed with L-glutamine (800 micromol x kg[-1] x h[-1]), the other day. Oral glutamine administration was associated with an 8% decrease in leucine release from protein breakdown, from 116 +/- 5 to 107 +/- 6 micromol x kg(-1) h(-1) (p < 0.01), and a 35% decrease in leucine oxidation rate from 23 +/- 2 to 15 +/- 2 micromol x kg(-1) x h(-1) (p < 0.01), resulting in no change in the nonoxidative leucine disposal, an index of protein synthesis. Whole body glutamine exchange in plasma doubled from 321 +/- 22 to 623 +/- 24 micromol x kg(-1) x h(-1), p < 0.01, but glutamine from protein degradation and glutamine de novo synthesis both decreased (91 +/- 4 versus 84 +/- 5 micromol x kg(-1) x h(-1), p < 0.01, and 230 +/- 21 versus 163 +/- 25 micromol x kg(-1) x (h-1), p = 0.02, respectively). These data suggest that acute oral glutamine administration might have a protein-sparing effect in children with Duchenne muscular dystrophy, decreasing estimates of whole body protein degradation and glutamine de novo synthesis, therefore sparing nitrogen precursors.
Abstract: Duchenne muscular dystrophy (DMD) is associated with a dramatic muscle mass loss. We hypothesized that DMD would be associated with significant changes in both energy and protein metabolism. We studied the resting energy expenditure (REE) in DMD and control children using indirect calorimetry, and their protein metabolism using an intravenous infusion of leucine and glutamine labeled with stable isotopes. In spite of a 75% muscle mass loss in the DMD children, the REE only decreased by 10%. DMD was associated with increased leucine oxidation but neither protein degradation nor protein synthesis were different from that of the controls. In contrast, whole body turnover of glutamine, an amino acid mainly synthesized in the muscle, was significantly decreased. These studies emphasized the quantitatively poor contribution of muscle to energy and protein metabolism in children. The qualitative impact of muscle mass loss on amino acid metabolism (glutamine) offers a fascinating field of research for the next few years and has therapeutic potential.
Abstract: Recently, significant incorporation of labeled carbon into plasma glucose was documented during infusion of 14C-labeled glutamine in postabsorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutamine carbon into glucose via glutamine entering Krebs cycle at alpha-ketoglutarate or 2) through simple fixation of labeled CO2 resulting from oxidation of labeled glutamine. Therefore, these studies were designed to determine 1) whether glutamine contributes carbon to gluconeogenesis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with fasting. Eight healthy adults were studied on two consecutive days: once after an overnight (18-h) fast and again on the second day of fasting (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-2H2lglucose, L-[3,4-13C2lglutamine, and L-[1-14C]leucine. Apparent rates of incorporation of glutamine carbon into glucose were estimated from the appearance of 13C into plasma glucose; glucose and glutamine production rates (appearance rate [Ra]) were determined from plasma [2H2]glucose and [13C2]glutamine enrichments, respectively. The appearance of 14C into plasma glucose was used to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur through other routes. We also observed that between 18 and 42 h of fasting, 1) the relative contribution of protein breakdown to glutamine production was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 +/- 1 to 16 +/- 3% of overall glucose Ra; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribution of glutamine to gluconeogenesis or mere carbon exchange between the trichloroacetic acid cycle and the gluconeogenic pathway. These findings are nevertheless compatible with a role of glutamine as a significant precursor of glucose in fasting humans.
Abstract: The aim of this study was to determine whether the putative protein anabolic effect of glutamine 1) is mediated by increased protein synthesis or decreased protein breakdown and 2) is specific to glutamine. Seven healthy adults were administered 5-h intravenous infusions of L-[1-14C]leucine in the postabsorptive state while receiving in a randomized order an enteral infusion of saline on one day or L-glutamine (800 mumol.kg-1.h-1, equivalent to 0.11 g N/kg) on the other day. Seven additional subjects were studied using the same protocol except they received isonitrogenous infusion of glycine. The rates of leucine appearance (RaLeu), an index of protein degradation, leucine oxidation (OxLeu), and nonoxidative leucine disposal (NOLD), an index of protein synthesis, were measured using the 14C specific activity of plasma alpha-ketoisocaproate and the excretion rate of 14CO2 in breath. During glutamine infusion, plasma glutamine concentration doubled (673 +/- 66 vs. 1,184 +/- 37 microM, P < 0.05), whereas RaLeu did not change (122 +/- 9 vs. 122 +/- 7 mumol. kg-1.h-1), OxLeu decreased (19 +/- 2 vs. 11 +/- 1 mumol.kg-1.h-1, P < 0.01), and NOLD increased (103 +/- 8 vs. 111 +/- 6 mumol. kg-1.h-1, P < 0.01). During glycine infusion, plasma glycine increased 14-fold (268 +/- 62 vs. 3,806 +/- 546 microM, P < 0.01), but, in contrast to glutamine, RaLeu (124 +/- 6 vs. 110 +/- 4 mumol. kg-1.h-1, P = 0.02), OxLeu (17 +/- 1 vs. 14 +/- 1 mumol.kg-1.h-1, P = 0.03), and NOLD (106 +/- 5 vs. 96 +/- 3 mumol.kg-1.h-1, P < 0.05) all decreased. We conclude that glutamine enteral infusion may exert its protein anabolic effect by increasing protein synthesis, whereas an isonitrogenous amount of glycine merely decreases protein turnover with only a small anabolic effect resulting from a greater decrease in proteolysis than protein synthesis.
Abstract: The high prevalence of obesity at an early stage of Duchenne muscular dystrophy (DMD) could result not solely from reduced physical activity, but may also involve low resting energy expenditure (REE), abnormal nutrient utilization, or overfeeding. We hypothesized that the dramatic muscle mass loss in DMD should reduce the REE. REE was measured by indirect calorimetry in 13 9-13-y-old DMD boys (5 obese, 8 nonobese) and 9 male age-matched controls. Muscle mass was estimated from 3-d creatinine excretion in urine. Daily energy intake was estimated from 7-d diet records. In the nonobese DMD group (NODMD) the muscle mass was reduced by 71%, and the REE was 13% lower than in controls (47.5 versus 54.6 kcal.h-1, p < 0.05). Postabsorptive respiratory quotients appeared higher in both DMD groups than in the controls; however, the difference was significant only for the NODMD group (0.88 versus 0.83, p < 0.05). Respiratory quotients were not different between the two DMD groups. Diet records were not contributive in revealing a different dietary behavior between groups. Our results suggest that: 1) muscle mass loss in DMD is associated with a low REE, 2) low postabsorptive fat utilization might occur at an early stage of the disease, and 3) obesity is not associated with an increase in fat utilization in DMD. This study warrants further research to test low REE and low fat utilization as risk factors in developing obesity in DMD.
Abstract: To determine whether exogenous glutamine affects whole body glutamine metabolism, preliminary experiments were performed to verify that L-[1-13C]-, L-[U-14C]-, and L-[3,4-3H]glutamine given simultaneously by vein provided similar estimates of glutamine appearance rates [Ra; 355 +/- 24, 373 +/- 19, and 393 +/- 24 (SE) mumol.kg-1.h-1, respectively, P = NS] in six healthy men; glutamine oxidation accounted for 32 +/- 3 and 51 +/- 5% (P < 0.01) of glutamine Ra when it was measured using L-[U-14C]- and L-[1-13C]glutamine, respectively. Five subjects received two 5-h intravenous infusions of L-[3,4-3H]glutamine and a simultaneous nasogastric infusion of L-[1-13C]glutamine on 2 separate days in the postabsorptive state, along with saline on 1 day and natural L-glutamine (856 +/- 45 mumol.kg-1.h-1) on another day in a randomized order. Splanchnic glutamine extraction (determined from [13C]glutamine appearance into systemic blood) reached 74 +/- 4 and 53 +/- 5% during the enteral infusion of tracer alone and in combination with a large load of glutamine, respectively. Glutamine infusion was associated with increased plasma glutamine concentration (from 630 +/- 50 to 1,297 +/- 75 microM), Ra (from 258 +/- 20 to 589 +/- 45 mumol.kg-1.h-1), and oxidation (from 179 +/- 20 to 477 +/- 47 mumol.kg-1.h-1, all P < 0.01), no change in glutamine release from proteolysis, and a decline in glutamine de novo synthesis (from 156 +/- 15 to 93 +/- 13 mumol.kg-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Because glutamine is thought to be a major fuel for developing gut, we tested the hypothesis that extensive small-bowel resection alters whole-body glutamine metabolism in vivo. Eleven infants and children who had undergone extensive small intestinal resection (residual bowel length: 35 +/- 13 cm; mean +/- SD) and four control infants received 4-h primed, continuous i.v. infusions of L-[(1-13C]leucine and L-[2-15N]glutamine in the postabsorptive state. The appearance rates of glutamine and leucine into plasma were determined from stable isotope enrichments in plasma at steady state. We observed the following: 1) Regardless of intestinal status, leucine and glutamine fluxes were higher in infants than values previously reported for adults. 2) Small-bowel resection was associated with a reduction in glutamine appearance rate (568 +/- 124 mumol.kg lean body mass-1.h-1 in short-bowel syndrome infants versus 816 +/- 149 mumol.kg lean body mass-1.h-1 in control infants; p < 0.05). 3) In contrast, leucine appearance rate was unaltered in short-bowel syndrome patients. The findings suggest that the small intestine plays a prominent role in glutamine metabolism in human infants.
Abstract: Rationale: A few studies reported malnutrition in hospitalized children in France, none of these were large scale multicenter. We designed a one-day cross-sectional survey in the third week of march 2011.
Methods: All participating centers followed the same procedure. Intensive care units and emergency rooms were excluded. All children admitted the same day were weighted and measured. A clinical examination was performed to any child with a BMI under the third percentile for age and sex. Results are presented as means ± SD.
Results: Fourteen paediatric units participated in the study all over France. On 1063 data collected, 952 were analysed. Only Children aged under 16 with specified weight and height were selected. Mean age was 6,5 ± 5,5 y (day 1 to 16 y). BMI < 3rd percentile for age and sex was found in 14,2 % of the whole population, and was associated with clinical signs of malnutrition in 9,0 %. Within 625 children with documented diagnostic, 52% were hospitalized for chronic diseases. Malnutrition was more frequent in children with chronic diseases (21 vs 8%, p<0,01). Highest prevalences of low BMI were observed in children with neurological (25%), metabolic, immune and endocrine (23%), cardiac (22%) or surgical (18%) diseases. BMI > 97th percentile was found in 14% of hospitalized children. Loss of muscle mass and handicap were best predictors of confirmed malnutrition.
Conclusion: This is the first french large scale multi-center study estimating malnutrition in hospitalized children. Next step will be to set up an European paediatric DDAY in order to promote nutritional care in children over EEC and compare participating countries with same tools and diagnostic procedures.
