BACKGROUND & AIMS:For adequate nutritional support of critically ill children, knowledge of the patient's energy expenditure is required. Steady state measurement by a metabolic monitor are defined as resting energy expenditure and may underestimate total energy expenditure in clinical practise. The aim of this study was to investigate total energy expenditure, resting energy expenditure and the relation with physical activity during critical illness and initial recovery. METHODS:We enrolled 20 patients (0-16 yr) with sepsis or following surgery. During the first week following admission, total energy expenditure was measured with doubly labelled water, and compared with daily resting energy expenditure measurements (metabolic monitor). Activity levels were independently determined by tri-axial accelerometry. RESULTS:Resting energy expenditure was not different from Schofield's predicted basal metabolic rate, but was 20% lower than total energy expenditure (P=0.006). Overall physical activity level (=total energy expenditure divided by resting energy expenditure) was 1.22 (95%CI: 1.08-1.36) and activity related energy expenditure (=total energy expenditure minus resting energy expenditure) was associated with accelerometry recordings (R(2)=0.72, P=0.02). CONCLUSIONS:During the week following pediatric intensive care admission, in the individual critically ill patient, activity related energy expenditure should be taken into account to prevent a negative energy balance.

Ornithine alphaketoglutarate (OKG) is known for its anabolic and anticatabolic effects. Little is known about its effect on proteolysis. We studied urea formation and nitrogen excretion rates following OKG supplementation in healthy volunteers. Sixteen male subjects were kept on a diet stable in protein (1 g kg−1 d−1) and aimed at maintaining body weight. They received oral supplementation of OKG (10 g) or an isonitrogenous placebo (l-alanine) from days 4 to 6 in single daily doses in a randomised, blinded fashion. Urea kinetics were studied on day 4 from plasma urea enrichments following an oral [13C]urea bolus. Nitrogen excretion was assessed from 24-h urine collections prior to supplementation, on day 4 and day 7. Mean urea rate of appearance was 380±86 and 353±120 μmol kg−1 h−1 in the OKG and placebo group, respectively (p=0.62). There were no significant differences in 24-h nitrogen excretion data between groups, neither at separate time points, in overall values (p=0.40) nor in development over time (p=0.53). A single oral dose of OKG did not affect urea production rate differently than the alanine placebo. OKG supplementation led to a temporary increase in nitrogen excretion, as did administration of placebo.

Objective: Longitudinal comparison of prescribed energy, actually administered energy, and energy expenditure (EE) predicted by Schofield's equations to actual EE, as determined by daily indirect calorimetry measurements in critically ill children during the first 7 days following admission. Design: Observational study. Setting: Pediatric intensive care unit, high and medium care wards, in a university hospital. Patients: Forty-six mechanically ventilated and spontaneously breathing infants and children (0–18 yrs) who were admitted with sepsis or following major abdominal or thoracic surgery or trauma. Interventions: Daily indirect calorimetry measurements and assessment of energy balance. Measurements and Main Results: Energy balance studies were performed for a total of 298 admission days in 13 sepsis, 27 surgery, and 6 trauma patients. Indirect calorimetry measurements were performed on 89% of the days. Mean measured EE was 44.6 ± 15 kcal/kg·d and equaled predicted EE (44.2 ± 12 kcal/kg·d; p = .56). Measured EE did not change over time, neither overall nor in diagnostic subgroups. Overall, median (range) administered energy was 31.1 (0–119) kcal/kg·d, which was significantly lower than measured EE (p < .001) and predicted EE (p < .001). Patients were underfed on 60% of days and overfed on 28% of days. Administered energy rose significantly in the course of admission, independently of diagnostic category, and did not differ from prescribed energy (p = .42). Energy intake was significantly higher in sepsis patients than in surgery and trauma patients during the whole course of the study (p < .01). The cumulative energy balance was positive only in sepsis patients. The administration of parenteral feeding was the single significant factor determining energy intake in mixed-effect modeling. Conclusions: Measured EE was stable and not significantly different from predicted values over the course of hospitalization. Underfeeding was frequently present and mainly due to prescription and administration of energy amounts inferior to measured EE values in enterally fed patients.

Background & aims: An oral [C-13]urea protocol may provide a simple method for measurement of urea production. The validity of single pool calculations in relation to a reduced sampling protocol was assessed.Methods: In eight fed and five fasted piglets, plasma urea enrichments from a 10 h sampling protocol were measured following an intragastric [C-13]urea bolus. Blood [C-13]bicarbonate was measured to trace gut [C-13]urea oxidation. Two-compartment and regression (single pool) computations were performed. Pool sizes were compared to urea distribution over total body water (TBW). Shorter protocol duration was tested in regression simulations.Results: Differences in urea kinetics between fed and fasted piglets did not reach statistical significance. Mean (+/-SE) urea pool from TBW times plasma urea concentration was 2.2+/-0.16 mmol kg(-1). Two-compartment modelling yielded similar results for pool size (despite the oxidation of a small amount of urea tracer). Urea appearance rate was 306+/-18 mumol kg(-1) h(-1). Regression calculations overestimated urea appearance rate vs. compartmental model (P < 0.05). When samples < 2 h were discarded, results were comparable to compartmental calculations even if protocol length was 6 h (325+/-24 mumol kg(-1) h(-1), NS).Conclusions: Regression calculations using plasma enrichments sampled between 2 and 6 h after oral [C-13]urea administration provide accurate rates of urea production, and are not affected by tracer oxidation. (C) 2004 Elsevier Ltd. All rights reserved.

Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects, using in vivo stable isotope methods. In addition, we determined the effect of folic acid on blood concentrations of amino acids which may have regulatory roles in homocysteine metabolism, i.e. homocysteine, AdoMet (S-adenosylmethionine), AdoHcy (S-adenosylhomocysteine), serine and glycine. Primed, continuous infusions with [2H3-methyl-1-13C]methionine were used to determine flux rates of methionine transmethylation, homocysteine remethylation and homocysteine trans-sulphuration. Metabolic homocysteine clearance was defined as the ratio of trans-sulphuration and plasma homocysteine level. Folic acid treatment increased the homocysteine remethylation rate by 59% [95% CI (confidence interval), 13-97%; P = 0.02] and methionine transmethylation rate by 20% (95% CI, 3-41%; P=0.03). Plasma total homocysteine concentration (-18%; 95% CI, -28 to -9%; P<0.01) and the serine/glycine ratio (-20%; 95% CI, -63 to -6%; P<0.01) decreased significantly, and the AdoMet/AdoHcy ratio (11%; 95% CI, 1-20%; P = 0.02) increased significantly. Changes in one-carbon flux rates did not correlate significantly with changes in plasma concentration of these amino acids. In conclusion, folic acid treatment lowered plasma homocysteine concentration and increased whole-body remethylation and transmethylation flux in healthy subjects.

Various α 1 -acid glycoprotein (AGP) glycoforms are present in plasma differing in extent of branching and/or fucosylation of their 5 N-linked glycans, as well as in concentration. It is assumed that hepatic synthesis determines the relative occurrence of the AGP-glycoforms in plasma, but experimental evidence is lacking. In this study, we have investigated the contribution of fractional synthesis rates to the plasma concentration of AGP-glycoforms that differed in relative occurrence in healthy human plasma. During a [ 13 C]valine infusion, AGP was isolated from the plasma of healthy volunteers. Four AGP-glycoforms, differing strongly in plasma concentration were obtained by sequential affinity chromatography over concanavalin-A- and Aleuria aurantia -agarose columns. The incorporation of the [ 13 C]valine tracer into the AGP-glycoforms was measured by gas chromatography combustion isotope ratio mass spectrometry. The mean fractional synthesis rates of the four AGP-glycoforms did not differ significantly between each other as well between individuals. The results indicated a renewal of about 15%/day of the plasma pools of each of the AGP-glycoforms. This is in support to the assumption that the differences in plasma concentration of the AGP-glycoforms are a reflection of the state of the hepatic glycosylation process. Published in 2004.

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at rest and during 90 min cycle exercise, using the deuterium-labeled water method. All subjects served as their own control: on one occasion they were studied in the fasting state, and on the second occasion they received an infusion of triacylglycerol plus heparin. At rest, the fractional rate of gluconeogenesis from pyruvate was higher in patients than in controls in the fasting state. Triacylglycerol infusion was associated with increased rates of GNG(PYR) at rest in controls (p < 0.05) but not in patients. Circulating lactate and pyruvate levels were increased 3-fold during exercise in the CID patients. During exercise, GNG(PYR) increased in the CID patients (p < 0.01) and remained unchanged in controls, resulting in 85% and 72% higher absolute rates of GNG(PYR) in the patients than in the controls during fasting and triacylglycerol infusion, respectively. During exercise, rates of GNG(PYR) were not different between fasting and triacylglycerol infusion within both groups. Our data show that 1) GNG(PYR) is increased during exercise in CID patients; 2) increased pyruvate availability contributes to the higher rates of GNG(PYR) in the CID patients; and 3) exogenous infusion of fatty acids is not associated with increased rates of GNG(PYR) in CID patients at rest or during exercise. GNG(PYR) is a significant mechanism of lactate disposal in exercising CID patients, but triglyceride infusion does not enhance their lactate disposal through this mechanism.

With intravenous infusion of doubly-labeled [2H3C-1-13C-] methionine and stable isotope enrichments in plasma free methionine and carbon dioxide in breath air, whole body transmethylation, transsulfuration, and remethylation rates can be calculated. This technique demonstrated impaired recycling as the major disturbance to explain hyperhomocysteinemia in patients with end-stage renal failure, and can be used to optimize interventions with folate, B6, and B12 supplementation in this patient group. Intravenous infusion of [2,3,3-2H3] serine has also been applied to demonstrate the appearance of [2H2]- as well as [2H1]-methionine in plasma and protein, suggesting transfer of a one-carbon group from serine via 5,10-methylenetetrahydrofolate in human hepatocyte cytosol and mitochondria, respectively. In sheep, tissue free methionine enrichments after infusion of universally labeled [U-13C] methionine showed the highest remethylation activity in postmortem investigation of jejunum, liver, and kidney tissue samples, but no such activity in muscle and brain samples. Methods to quantitate one-carbon acceptor metabolism pathways and folate metabolism have recently become available.

BACKGROUND:A high-fat diet has been recommended for correction of biochemical abnormalities and muscle energy state in patients with complex I (NADH dehydrogenase) deficiency (CID). OBJECTIVE:This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate oxidation, glycolytic carbohydrate metabolism, and energy state in patients with CID. DESIGN:Four CID patients and 15 matched control subjects were infused with triacylglycerol (1.85 mg x kg(-1) x min(-1)) or glucose (5 mg x kg(-1) x min(-1)) while at rest. Respiratory calorimetry was used to evaluate mitochondrial substrate oxidation. Metabolism of glycolytic carbohydrate was determined on the basis of the rates of appearance and concentrations of plasma lactate from dilution of [1-(13)C]lactate measurements. In addition, high-energy phosphate metabolism was measured in forearm muscle by (31)P magnetic resonance spectroscopy. RESULTS:Whole-body oxygen consumption rates were higher in the patients than in the control subjects (P < 0.05). Oxygen consumption and high-energy phosphate metabolism in forearm muscle were not significantly different between the 2 infusion groups. The rates of appearance and concentrations of plasma lactate were higher in each of the 4 patients than in the control subjects (P < 0.05) and were lower during the triacylglycerol infusion than during the glucose infusion (P < 0.05); the differences were comparable in the patients and control subjects. CONCLUSIONS:We conclude that triacylglycerol infusion, relative to glucose infusion, does not improve the oxidation of substrates or the energy state of skeletal muscle and does not lower the rates of appearance and concentrations of plasma lactate to normal values in CID patients at rest.

We tested the hypothesis that some cereal-product vehicles may reduce fortificant bioavailability below 85% and examined the feasibility of using single dose, dual-label, non-saturation protocols for studying bioavailability based on urinary excretion ratios (UER; % oral 13C6 isotope dose excreted in intact folate/% IV 2H4 isotope dose excreted). Fifteen females received 225 μg oral folate (capsules, fortified bran flakes, and fortified white bread), mainly as 13C6-PteGlu, followed by IV injection of 100 μg 2H4-PteGlu. UERs were used as the primary index of absorption. Urinary folate was cleaved to p-aminobenzoylglutamic acid, dervivatized and determined by gas chromatography/mass spectroscopy (GC/MS). The UER mean (95%CI) for folic acid was 2.18 (1.2-3.8) at 48 hours and as these were greater than 1.0, it was concluded that oral and IV isotopes of folic acid are handled differently by the body. Compared to the 48 hour UER for folic acid, UERs for white bread and bran flakes were 0.71 and 0.37, respectively, thus indicating some matrix inhibition of absorption. Consideration should be given to the choice of cereal-based fortification vehicles in order to maximize bioavailability. Plasma enrichment of folate can be measured using LC/MSMS (liquid chromatography/mass spectroscopy-mass spectroscopy) but seems unfeasible with the GC/MS method.

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-C-13]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha(2)-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.

To explore how nurses manage personal and professional boundaries in caring for seriously ill children and their families.Using a constructivist grounded theory approach, a convenience sample of 18 registered nurses from four practice sites was interviewed using a semi-structured interview guide.Nurses across the sites engaged in a process of maintaining integrity whereby they integrated two competing, yet essential, aspects of their nursing role – behaving professionally and connecting personally. When skillful in both aspects, nurses were satisfied that they provided high-quality, family-centered care to children and families within a clearly defined therapeutic relationship. At times, tension existed between these two aspects and nurses attempted to mitigate the tension. Unsuccessful mitigation attempts led to compromised integrity characterized by specific behavioral and emotional indicators. Successfully mitigating the tension with strategies that prioritized their own needs and healing, nurses eventually restored integrity. Maintaining integrity involved a continuous effort to preserve completeness of both oneself and one's nursing practice.Study findings provide a theoretical conceptualization to describe the process nurses use in navigating boundaries and contribute to an understanding for how this specialized area of care impacts health care providers.Work environments can better address the challenges of navigating boundaries through offering resources and support for nurses' emotional responses to caring for seriously ill children. Future research can further refine and expand the theoretical conceptualization of maintaining integrity presented in this paper and its potential applicability to other nursing specialties.

The impact of child deaths on the nutrition status of surviving children in the Lake Titicaca basin in the Andes of southern Peru (altitude>3,800 m) is explored. Survey data on obstetric history and social variables were collected in a random sample of 86 households in two Aymara and three Quechua Amerindian peasant communities. Independently of social factors, deaths among older siblings under five years old were associated with improved nutrition stature in children under four. Improved head circumference for age in boys was associated with the death of an older sister. The findings point to a new hypothesis concerning nutrition status in this population: mortality in children under five can be related to improved nutrition status (as evidenced by head circumference and height) in surviving siblings under four.