Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome

Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine supplement with parenteral nutrition decreases whole body proteolysis in low birth weight infants

OBJECTIVES: To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 ) on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW) infants receiving parenteral nutrition in the immediate neonatal period. STUDY DESIGN: Premature infants < or =32 weeks gestation with a birth weight from 694 to 1590 g were randomly assigned to either a glutamine-supplemented group (n = 10) or to a control group (n = 10). Tracer isotope studies were performed when the infants were 6 to 7 days old and had been receiving an amino acid intake of approximately 3.0 g.kg -1 .d -1 for at least 3 days. Whole body glutamine and nitrogen kinetics were measured with [5-15N]glutamine, [2H5]phenylalanine, [1-13C, 15 N]leucine, [15N2]urea, and GC-mass spectrometry. RESULTS: Supplemental glutamine was associated with a lower rate of appearance of glutamine ( P = .003), phenylalanine ( P = .001), and leucine C ( P = .003). There was no significant difference in leucine N turnover, urea turnover and plasma cortisol, and C-reactive protein levels in the 2 groups. CONCLUSION: Parenteral glutamine supplement in LBW infants was associated with lower whole-body protein breakdown. Because the decrease in whole body proteolysis is associated with protein accretion, parenteral glutamine supplement may be beneficial in selected populations of LBW infants.     

Effects of early amino acid administration on leucine and glucose kinetics in premature infants

We previously showed that, in prematurely born infants, an anabolic state without metabolic acidosis can be achieved upon intravenous amino acid (AA) administration in the immediate postnatal phase, despite a low energy intake. We hypothesized that the anabolic state resulted from an increased protein synthesis and not a decreased proteolysis. Furthermore, we hypothesized that the energy needed for the higher protein synthesis rate would be derived from an increased glucose oxidation. To test our hypotheses, 32 ventilated premature infants (<1500 g) received intravenously either solely glucose or glucose and 2.4 g AA/kg/d immediately postnatally. On postnatal d 2, each group received primed continuous infusions of either [1-13C]leucine or [U-13C6]glucose. 13CO2 enrichments in expiratory air and plasma [1-13C]alpha-KICA (as an intracellular leucine precursor) and [U-13C6]glucose enrichments were measured by mass spectrometry techniques. The AA administration resulted in an increased incorporation of leucine into body protein and a higher leucine oxidation rate, whereas leucine release from proteolysis was not affected. Glucose oxidation rate did not increase upon AA administration. In conclusion, the anabolic state resulting from AA administration in the immediate postnatal period resulted from increased protein synthesis and not decreased proteolysis. The energy needed for the additional protein synthesis was not derived from an increased glucose oxidation.     

Amino acids, glutamine, and protein metabolism in very low birth weight infants

Glutamine has been proposed to be conditionally essential for premature infants, and the currently used parenteral nutrient mixtures do not contain glutamine. De novo glutamine synthesis (DGln) is linked to inflow of carbon into and out of the tricarboxylic acid (TCA) cycle. We hypothesized that a higher supply of parenteral amino acids by increasing the influx of amino acid carbon into the TCA cycle will enhance the rate of DGln. Very low birth weight infants were randomized to receive parenteral amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5-(15)N]glutamine, [2H5]phenylalanine, [1-(13)C,15N]leucine, and [15N2]urea tracers. An acute increase in parenteral amino acid infusion for 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext). These data show an acute increase in parenteral amino acid-suppressed proteolysis, however, such an effect was not seen when amino acids were infused for 20 h and resulted in an increase in glutamine synthesis.     

Whole body protein turnover measured with 13C-leucine and energy expenditure in preterm infants

Our study was undertaken in preterm infants to examine the relationship of whole body protein kinetics with protein intake and energy expenditure. Leucine kinetics were determined in seven low birth wt preterm infants fed human milk or human milk enriched with protein (2.5 to 4.3 g protein/kg.d). The infants received a short (4-h) constant infusion of L-[1-13C]leucine and leucine turnover and oxidation were calculated from 13C-plasma leucine and expired 13CO2 enrichments measured by mass spectrometry. Energy expenditure was measured by indirect calorimetry. Nonoxidative leucine disposal (an estimate of protein synthesis) and leucine derived from protein (an estimate of protein breakdown) were, respectively, 2.98 +/- 0.82 and 2.06 +/- 0.74 mumol/kg.min. Whole body protein turnover and deposition, derived from leucine kinetics, were 8.22 +/- 2.31 and 2.17 +/- 0.50 g/kg.d, whereas energy expenditure was 56.3 kcal/kg.day. Protein turnover was correlated with protein intake but not with protein deposition. Energy expenditure was correlated with protein turnover, synthesis, and breakdown but not with protein deposition. These data are in agreement with the fact that protein deposition depends upon protein intake, but they also suggest that an elevated protein deposition is not necessarily the result of a rapid protein turnover or associated with an elevated energy expenditure.     

Whole-body protein parameters in premature infants: a comparison of different 15N tracer substances and different methods.

[15N]glycine, [15N]leucine, and [15N]yeast protein thermitase hydrolysate (YPTH) as tracers for investigating the protein turnover rates in premature infants were studied in nine human milk-fed neonates (born after 32 to 34 wk of gestation) by paired comparison of the tracers. The 15N enrichment of total urinary nitrogen and ammonia after administration of a single oral dose of 15N was measured by emission spectrometry. Flux rates were calculated using a three-compartment model and the ammonia end product method. The mean whole-body protein synthesis rates, as determined by the three-compartment model derived from the three 15N tracers, differed significantly (p less than 0.01) among [15N]glycine (15.9 g/kg/d), [15N] leucine (9.1 g/kg/d), and 15N-YPTH (5.9 g/kg/d). When the corresponding rates were determined from the excretion of label in ammonia, the results showed the opposite tendency; the lowest apparent synthesis rates were found after [15N]glycine (7.5 g/kg/d), followed by [15N]leucine (14.4 g/kg/d), and the highest figure resulted after [15N] YPTH (16.7 g/kg/d). The results of this comparison substantiate the assumption that there are methodologic errors in connection with the use of different tracers and models for the calculation of whole-body protein parameters in preterm infants, with respect to the main requirement for tracer kinetic studies; the tracer nitrogen must be representative of total amino acid nitrogen. Seen in this light, mixtures of completely labeled amino acids such as YPTH may represent the most reliable tracer substance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole body protein turnover and urea production of preterm small for gestational age infants fed fortified human milk or preterm formula

OBJECTIVES: To investigate protein metabolism and urea production in preterm small for gestational age neonates fed a preterm formula or fortified human milk. METHODS: Ten preterm small for gestational age neonates were fed either their own mother's milk fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1-13C]valine. Urea production was determined from steady-state [13C]urea kinetics. RESULTS: Mean protein intake was 24% higher in the preterm formula group than in the fortified human milk group. No differences in protein turnover, synthesis and breakdown were observed between the two groups, but protein accretion was 71% to 79% higher in the preterm formula group than the fortified human milk group. Urea production rates were not different in the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics. CONCLUSIONS: Preterm formula and fortified human milk appear equally well tolerated by preterm small for gestational age neonates, but protein accretion was higher in the preterm formula group. In preterm small for gestational age infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.     

Minimum protein intake for the preterm neonate determined by protein and amino acid kinetics

Lower limits of protein needs in prematurely born neonates have not been adequately studied, yet providing protein in amounts maximizing accretion without excess is a goal in these infants' nutritional care. We hypothesized that with the use of amino acid oxidation methodology, it would be possible to define minimum protein requirement. Our objective was to investigate protein kinetics during short-term changes in protein intake by measurement of nitrogen balance and amino acid flux and oxidation using [(15)N]glycine, [(13)C]phenylalanine, and [(13)C]leucine tracers. Protein kinetics were examined in 21 preterm infants (gestational age: 29 +/- 3 wk; birth weight: 1091 +/- 324 g) at five protein intakes (1.0, 1.5, 2.0, 2.5, and 3.0 g x kg(-1) x d(-1)) with 1 d of adaptation to the test intakes. From nitrogen balance data, a protein need of 0.74 g x kg(-1 x -1) was estimated to achieve zero balance. For all three amino acids, flux and oxidation estimates were not different across protein intakes. Whole-body protein synthesis and breakdown estimates from [(15)N]ammonia data were 14.6 +/- 3.4 and 14.4 +/- 4.1 g x kg(-1) x d(-1), respectively. Glycine flux (680 +/- 168 micromol x kg(-1) x h(-1)) was greater than leucine flux (323 +/- 115 micromol x kg(-1) x h(-1)), which was greater than phenylalanine flux (84.3 +/- 35.2 micromol x kg(-1) x h(-1)). Leucine oxidation (36.7 +/- 15.6 micromol x kg(-1) x h(-1)) was also greater than phenylalanine oxidation (6.64 +/- 4.41 micromol x kg(-1) x h(-1)). Infants in our study were able to adapt to short-term changes in protein intake with little consequence to the overall whole-body protein economy, as measured by the three test amino acids.     

Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover, we studied the leucine turnover in preterm infants soon after birth and again after 7 days. Ten infants from preeclamptic mothers (birth weight 1,280 +/- 240 g, gestational age 31 +/- 2 weeks) and 15 control patients (birth weight 1,320 +/- 210 g, gestational age 30 +/- 2 weeks) were enrolled. The leucine turnover was measured using a primed constant 5-hour intravenous infusion of [1-(13)C]leucine within the first 24 h after delivery and again on day 7 of life. The turnover (leucine flux; micromol.kg(-1).h(-1)) was calculated from the enrichment in alpha-ketoisocaproic acid in plasma. The leucine turnover on day 1 was 300 +/- 65 in the preeclampsia group and 358 +/- 70 in the controls (ANOVA, p < 0.05). The values on day 7 were 474 +/- 73 in the preeclampsia group and 485 +/- 80 in the control group (n.s.). To conclude, the leucine turnover on day 1 is lower in infants of preeclamptic mothers as compared with controls. This difference has disappeared on day 7 of life after receiving the same protein and energy intake.     

Changes in protein turnover after the introduction of parenteral nutrition in premature infants: comparison of breast milk and egg protein-based amino acid solutions.

Rates of protein turnover were measured in 20 infants receiving either Vamin Infant (group A) or Vamin 9 glucose (group B) as the amino acid source in total parenteral nutrition. A constant infusion of L-[1-13C]leucine was used to measure whole body leucine flux, and leucine oxidation rates were derived from measurements of total urinary nitrogen excretion. Infants were first studied when receiving only i.v. glucose and again on each of the next 4 d as total parenteral nutrition was gradually increased to a maximum of 430 mg nitrogen/kg/d and 90 nonprotein kcal/kg/d. Net protein gain and protein synthesis and breakdown rates increased progressively for all infants taken together over the study period as i.v. nutrition was increasing (p less than 0.001). There were no differences between groups in the changes in net protein gain and rates of protein synthesis and breakdown throughout the study period. Nitrogen retention on d 5 for the two groups was similar (60 +/- 16% and 67 +/- 11% in groups A and B, respectively). In a subgroup of infants, measurements were repeated on d 8, when the intake had been constant for 3 d. Protein retention was the same as on d 5, but both synthesis and breakdown were increased. It is concluded that rates of protein turnover increase significantly in response to increasing i.v. nutrition and that this elevation was not influenced by the composition of the amino acid mixture given.     

Effect of insulin with concurrent amino acid infusion on protein metabolism in rapidly growing pubertal children with type 1 diabetes

Insulin treatment of prepubertal children with insulin-dependent diabetes improves body protein balance by decreasing the rate of protein degradation without stimulating protein synthesis. However, insulin also causes hypoaminoacidemia, so the inability of insulin to stimulate protein synthesis may have been limited by substrate availability. We investigated the ability of insulin to stimulate protein synthesis in growing pubertal children who were given sufficient amino acids to counter insulin-induced hypoaminoacidemia. Protein metabolism in six pubertal children with type 1 diabetes was assessed from leucine kinetics during a primed, 6-h infusion of L-[1-(13)C]leucine. The children were studied in the postabsorptive state during a basal (insulin withdrawn) period and during the infusion of 0.83 mU * kg(-1) * min(-1) human regular insulin. Amino acids and glucose were given with insulin to prevent hypoaminoacidemia and hypoglycemia. Net leucine balance was significantly higher with insulin than in the basal state, the result of decreased protein degradation but also decreased protein synthesis. The data suggest that insulin alone does not increase protein synthesis in pubertal children with type 1 diabetes.     

Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study.

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.     

Effect of minimal enteral feeding on splanchnic uptake of leucine in the postabsorptive state in preterm infants

We conducted a controlled, randomized trial to study the effect of minimal enteral feeding on leucine uptake by splanchnic tissues, as an indicator of maturation of these tissues, in preterm infants in the first week of life. Within a few hours after birth, while receiving only glucose, a primed constant infusion of [1-(13)C]-leucine was started and continued for 5 h via the nasogastric tube, whereas 5,5,5 D3-leucine was infused intravenously (for both tracers, priming dose 2 mg/kg, continuous infusion 2 mg/kg/h). Patients were thereafter randomized to receive solely parenteral nutrition (C), parenteral nutrition and 20 mL breast milk/kg/d (BM), or parenteral nutrition and 20 mL formula/kg/d (F). On d 7, the measurements were repeated, after discontinuing the oral intake for 5 h. Fourteen infants were included in group C, 12 in group BM, and 12 in group F. There was no difference in energy intake or nitrogen balance at any time. On d 1, plasma enrichment for the nasogastric tracer was lower than for the intravenous tracer for all three groups, both for leucine and for alpha-keto-isocaproic acid. On d 7, the enrichment for leucine and alpha-keto-isocaproic acid for the nasogastric tracer was lower than for the intravenous tracer for the groups BM and F (BM: 3.65 +/- 1.20 nasogastric versus 4.64 +/- 0.64 i.v.; F: 4.37 +/- 1.14 nasogastric versus 5.21 +/- 0.9 i.v.). In the control group, there was no difference between tracers. The lower plasma enrichment for the nasogastric tracer compared with the intravenous tracer suggests uptake of leucine by the splanchnic tissues. We conclude that minimal enteral feeding--even in low volumes of 20 mL/kg/d--increases the leucine uptake by the splanchnic tissue. We speculate that this reflects a higher protein synthesis of splanchnic tissues in the groups receiving enteral nutrition.     

A dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia

The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 +/- 0.2; gestational age, 39.8 +/- 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 +/- 0.3 kg; gestational age, 39.1 +/- 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 di-palmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean +/- SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 +/- 2.2 and 8.1 +/- 1.5 mg. kg(-1). d(-1); P = 0.7). DSPC apparent pool size was 36.7 +/- 7.5 and 58.5 +/- 9.1 mg/kg (P = 0.07) and half-life was 26.7 +/- 4.5 and 50.3 +/- 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was approximately 8 mg. kg(-1). d(-1). No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.     

Leucine kinetics during feeding in normal newborns

To examine how leucine and protein metabolism is affected by feeding, leucine kinetics were determined in 11 normal term newborns during feeding using a prime constant tracer infusion of 1-13C leucine combined with respiratory calorimetry. Fed newborns were compared with previously studied fasting newborns. Feeding and fasting newborns had similar rates of leucine oxidation (34 +/- 3 mumol/kg/h versus 31 +/- 4 mumol/kg/h) and leucine release from existing protein (156 +/- 16 mumol/kg/h versus 164 +/- 8 mumol/kg/h). In contrast, nonoxidative disposal rates of leucine (a reflection of protein synthesis) were significantly greater in feeding newborns (170 +/- 13 mumol/kg/h versus 129 +/- 9 mumol/kg/h). A significant positive correlation between birth weight and leucine flux was demonstrated in both feeding and fasting newborns. These results suggest that 1) newborns may accomplish protein accretion primarily by increases in protein synthesis rather than suppression of protein breakdown; 2) an estimate can be made of the minimal leucine intake required to replace irreversible leucine oxidative losses (816 mumol/kg/d, 107 mg/kg/d); and 3) the positive correlation between birth weight and leucine flux in both feeding and fasting newborns may be a result of differences in previous protein and energy supplies.     

Validation of a [13C]bicarbonate tracer technique to measure neonatal energy expenditure

The use of a stable isotope-labeled [13C]bicarbonate infusion to measure energy expenditure is advantageous, as a complete collection of expired air is not required. This technique allows for facile measurements of energy expenditure in intubated neonates. The aim of the present study was to determine the accuracy of energy expenditure estimates in postsurgical neonates by using the [13C]bicarbonate method compared with the current standard, indirect calorimetry. Eight neonates who were receiving total parenteral nutrition [98 +/- 21 (SD) kcal x kg(-1) x d(-1); 3.1 +/- 0.7 (SD) protein g x kg(-1) x d(-1)] were studied on postoperative d 15.5 +/- 11.9. A primed continuous 3-h intravenous infusion of NaH13CO3 and indirect calorimetry were performed simultaneously. Energy expenditure was calculated separately from the Weir equation and from the dilution of 13CO2 in the breath in combination with the individual energy equivalents of CO2 from the diet. The rate of CO2 appearance and energy expenditure calculated from the bicarbonate method (0.725 +/- 0.021 mol x kg(-1) x d(-1); 89.5 +/- 2.5 kcal x kg(-1) x d(-1)) highly correlated (r = 0.94 and 0.98, respectively) with the CO2 excretion and energy expenditure determined by indirect calorimetry (0.489 +/- 0.016 mol x kg(-1) x d(-1); 60.2 +/- 2.0 kcal x kg(-1) x d(-1)) when analyzed nonproportionately to weight. Bland-Altman analysis demonstrated the 95% confidence interval to be +/- 8.2 kcal x kg(-1) x d(-1). Linear regression analysis revealed a highly statistically significant equation relating the two energy expenditures: Indircal (kcal/d) = -9.341 + [0.705 x Bicarb (dcal/d)]; p < 0.001, r2 = 96.4%. We conclude that energy expenditure in neonates can be accurately determined using the [13C]bicarbonate method and a regression equation. Therefore, the bicarbonate method may be useful for determining energy expenditure in neonates not readily accessible to indirect calorimetry, such as those being mechanically ventilated or on extracorporeal life support.     

Effect of insulin on leucine kinetics in maple syrup urine disease

Leucine turnover was measured using [1-14C] L-leucine in three patients with classical maple syrup urine disease. There was measurable leucine oxidation although it was lower than in normal adults. Leucine production rate was greater than normal in all three patients with an increased rate of incorporation of leucine into protein and increased protein catabolism. These fluxes were both relatively insensitive to exogenous insulin.     

Protein turnover rates in sick, premature neonates during the first few days of life.

Rates of protein turnover were measured in 19 infants during the first few days of life while they were receiving i.v. glucose. The technique consisted of a continuous i.v. infusion of L-[1-13C]leucine to measure whole body leucine flux and determination of total urinary nitrogen excretion to assess leucine oxidation rates. Subsequent to each of the studies, the decision to start total parenteral nutrition (TPN) was made by the clinician concerned, with the result that seven infants did not start TPN and 12 did. There were significantly greater urinary nitrogen excretion (p less than 0.001) and lower rates of whole body protein synthesis (p = 0.024) and breakdown (p = 0.015) in those who did start TPN compared with those who did not. The marked difference in nitrogen excretion between the two groups suggests that this could be a useful determinant for deciding which neonate should start TPN.     

Corticosteroids increase protein breakdown and loss in newly diagnosed pediatric Crohn disease

Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-α therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-(13)C] leucine, and [(15)N(2)] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition.