Kees de Meer

Energy expenditure and balance following pediatric intensive care unit admission: a longitudinal study of critically ill children.

Objective: Longitudinal comparison of prescribed energy, actually administered energy, and energy expenditure (EE) predicted by Schofields 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.

Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects.

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.

Distinct glycoforms of human α1-acid glycoprotein have comparable synthesis rates: a [13C]valine-labelling study in healthy humans

Various α1-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 [13C]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 [13C]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.