Papers by Johannes Van Goudoever
The Faseb Journal, Apr 1, 2007
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Amer J Physiol Gastrointest L, 2006
synthesis in preterm infants on the first day of life studied with [1-13 C]leucine. min is the ma... more synthesis in preterm infants on the first day of life studied with [1-13 C]leucine. min is the major binding protein in the human neonate. Low production of albumin will lower its transport and binding capacity. This is especially important in preterm infants, in whom albumin binds to potentially toxic products such as bilirubin and antibiotics. To study the metabolism of plasma albumin in preterm infants, we administered a 24-h constant infusion of [1-13 C]leucine to 24 very low birth weight (VLBW) infants (28.4 Ϯ 0.4 wk, 1,080 Ϯ 75 g) on the first day of life. The caloric intake consisted of glucose only, and therefore amino acids for albumin synthesis were derived from proteolysis. The fractional synthesis rate (FSR) of plasma albumin was 13.9 Ϯ 1.5%/day, and the absolute synthesis rate was 148 Ϯ 17 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 . Synthesis rates were significantly lower (P Ͻ 0.03) in infants showing intrauterine growth retardation. Albumin synthesis increased with increasing SD scores for gestation and weight (P Ͻ 0.05). The FSR of albumin tended to increase by 37% after administration of antenatal corticosteroids to improve postnatal lung function (P ϭ 0.09). We conclude that liver synthetic capacity is well developed in VLBW infants and that prenatal corticosteroids tend to increase albumin synthesis. Decreased weight gain rates in utero have effects on protein synthesis postnatally. synthesis of albumin; intrauterine growth retardation; gas chromatography-isotope ratio mass spectrometry
Background: Cyst(e)ine can be synthesized de novo from methionine and serine and is, therefore, a... more Background: Cyst(e)ine can be synthesized de novo from methionine and serine and is, therefore, a nonessential amino acid in human adults. Several studies have suggested that cyst(e)ine might be a conditionally essential amino acid in preterm infants because of biochemical immaturity. No data are available on cyst(e)ine requirements in low-birth-weight (LBW) preterm infants. Objective: The aim was to determine cyst(e)ine requirements in LBW infants with gestational ages from 32 to 34 wk, measured 1 mo after birth with the use of the indicator amino acid oxidation technique. Design: LBW infants were randomly assigned to 1 or 2 of the 5 formulas containing graded cystine concentrations (11, 22, 32, 43, or 65 mg cyst(e)ine/100 mL) and generous amounts of methionine. After 24-h adaptation, cyst(e)ine requirement was determined by 13 CO 2 release from [1-13 C]phenylalanine in expired breath. 13 CO 2 enrichment was measured by isotopic ratio mass spectrometry. Results: Cyst(e)ine requirement was determined in 25 LBW infants with a mean (ȀSD) gestational age of 33 Ȁ 1 wk and birth weight of 1.78 Ȁ 0.32 kg. Fractional oxidation of [1-13 C]phenylalanine did not differ between the 5 groups. Conclusions: There is no evidence for limited endogenous cyst(e)ine synthesis in 4-wk-old LBW preterm infants born at gestational ages from 32 to 34 wk. It is safe to conclude that the cyst(e)ine requirement is 18 mg ⅐ kg Ҁ1 ⅐ d Ҁ1 providing generous amounts of methionine and that cyst(e)ine is probably not a conditionally essential amino acid in fully enterally fed LBW preterm infants born at 32-34 wk.
Clinical Nutrition, May 1, 2009
Pediatric Research, 2015
Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additi... more Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additional indicator of ID in preterm infants, next to ferritin. In a prospective observational study we analyzed serum hepcidin in 111 infants born after 32+0 to 36+6 weeks gestational age during the first four months of life. Hepcidin concentrations decreased during the first four months of life, and concentrations were lower in infants with ID compared to those without ID. Infants who developed ID at the age of four months had already significantly lower levels of hepcidin at 1.5 months of age, while ferritin was already significantly lower at the age of one week. Hepcidin concentrations of late preterm infants decrease during the first four months of life. This decrease, which parallels a decrease of ferritin concentration, we interpret as a physiological response, aiming to increase iron availability. Hepcidin concentrations are lower in infants with ID compared to those without ID, with a notable change already observed at 1.5 months of age. Hepcidin can be used as an early marker of ID, although an additive value of hepcidin over ferritin in the diagnosis of ID is not present.Pediatric Research (2015); doi:10.1038/pr.2015.258.
Journal of Pediatric Gastroenterology and Nutrition, Dec 1, 2006
Objectives: Bowel segments distal to a congenital intestinal obstruction have been suggested to b... more Objectives: Bowel segments distal to a congenital intestinal obstruction have been suggested to be immature. In other words, luminal components such as amniotic fluid (before birth) and/or enteral nutrition (after birth) may be required to activate intestinal epithelial protein expression, thereby influencing epithelial differentiation. We investigated cell-type-specific protein expression proximal and distal to jejunal and ileal atresias in human newborns. Patients and Methods: We immunohistochemically studied intestinal tissue specimens of 16 newborns who had undergone surgery for jejunal or ileal atresia. Sections were taken from both the proximal and distal sides of the atresias. Results: For all patients, the enterocyte-specific markers lactase, sucrase-isomaltase, sodium glucose cotransporter 1, glucose transporters 2 and 5, intestinal fatty acid-binding protein and alkaline phosphatase were expressed at a mean 3 AE 1 days after birth, both proximal and distal to jejunal and ileal atresias. Expression of goblet cell-specific markers mucin 2 and trefoil factor 3 and that of the Paneth cell marker lysozyme was maintained at either side of the atretic segment. Conclusions: With respect to the markers used, the human small intestinal epithelium is already differentiated shortly after birth. The absence of intestinal continuity in case of a jejunal or ileal atresia does not affect epithelial protein expression. This would seem to indicate that the developing small intestinal epithelium matures independently of luminal components. JPGN 43: 576-583, 2006.
Current Opinion in Clinical Nutrition and Metabolic Care, 2010
Premature infants often suffer from suboptimal outcome, at least partially due to suboptimal nutr... more Premature infants often suffer from suboptimal outcome, at least partially due to suboptimal nutrition. Gaining insight into human fetal amino acid metabolism might ultimately lead to an improved nutritional strategy for prematurely born infants. Our aim was, therefore, to discuss recent findings with regard to human fetal amino acid metabolism. Human fetal protein and amino acid metabolism can be studied in vivo using stable isotope techniques. To date, however, only a few studies employing these techniques have been performed. For one, it was shown in vivo that essential amino acids are transported at different rates across the human placenta. In addition, tyrosine appears not to be a conditionally essential amino acid in the fetus at term, as phenylalanine is hydroxylated into tyrosine at considerable rates. Furthermore, albumin is synthesized at very high rates at two-thirds of gestation; higher than prematurely born infants do at a neonatal intensive care unit. This could indicate that postnatal nutrition of very immature infants can be improved. Although technically challenging, more studies regarding human fetal amino acid metabolism should be performed. Premature infants could then benefit from this knowledge from new nutritional strategies.
The American Journal of Clinical Nutrition, Sep 1, 2003
Background: Preterm infants often receive total parenteral nutrition (TPN) before enteral feeding... more Background: Preterm infants often receive total parenteral nutrition (TPN) before enteral feeding. Although TPN has been linked to mucosal atrophy, its effects on intestinal digestion, absorption, and metabolism are unknown. Objective: Our aim was to determine the effects of TPN on rates of intestinal nutrient absorption and metabolism in infant pigs after initiation of enteral feeding. Design: Piglets were surgically implanted with catheters in the carotid artery, jugular vein, portal vein, and duodenum; an ultrasonic blood flow probe was inserted in the portal vein. Piglets were given TPN (TPN group) or enterally fed formula (enteral group) for 6 d. On day 7, both groups were enterally fed a milkbased formula, and the net portal absorption and metabolism of enteral [ 2 H]glucose and [ 13 C]leucine were measured. Results: After enteral feeding began, portal blood flow increased by 27% and 41% above the basal rate in the enteral and TPN groups, respectively; oxygen consumption remained lower in the TPN group. During enteral feeding, the net portal absorption of glucose was lower in the TPN group and that of galactose was not significantly different between the groups; lactate release was higher in the TPN group. Portal absorption accounted for only Ϸ37% of galactose intake in both groups. The TPN group had lower net portal absorption of arginine, lysine, threonine, and glycine. The portal absorption of dietary leucine was not significantly different between the groups; the arterial utilization and oxidation of leucine were significantly lower in the TPN group. Conclusion: Short-term TPN results in decreased lactose digestion and hexose absorption and increased intestinal utilization of key essential amino acids when enteral feeding is initiated in piglets.
Gastroenterology, 2008
in normal fetal and adult tissues. To evaluate long-term effects of the endothelin system on epit... more in normal fetal and adult tissues. To evaluate long-term effects of the endothelin system on epithelial cells we used a modification of the 3D organotypic system, where ET3 is continuously produced by the embedded fibroblasts as a result of adenovirus-mediated gene transfer and monitored using ELISA. Effects on proliferation were assessed by BrdU incorporation and Ki67 immunohistochemistry, and the absorptive and secretory lineages were evaluated with lineage specific markers. Results: In 2D culture, ET3 stimulated in a dose-dependent manner proliferation of normal colonic cells. Use of both ETRA and -B inhibitors blocked the proliferation of epithelial cells below that observed in controls. In organotypic cultures, ET3 increased the number of BrdU positive epithelial cells and the number of goblet cells but not of enteroendocrine cells. Inhibition of both ETRA and ETRB by peptide inhibitors significantly decreased proliferation and the number of goblet cells, while the number of enteroendocrine cells remained unchanged. Both inhibitors were required to suppress proliferation of normal colonic epithelial cells. ET3 induced activation of IκB and MAPK, suggesting that these signaling pathways mediate its pro-proliferation and pro-survival activities. Conclusions: Our results indicate that the endothelin system is involved in regulation of normal human colonic epithelial homeostasis, especially epithelial and goblet cells, and provides new insights into how a paracrine factor may modulate survival of different cell types.
The Clinical Journal of Pain, Oct 1, 2009
Objectives: Pain assessment is essential to tailor intensive care of neonates. The present focus ... more Objectives: Pain assessment is essential to tailor intensive care of neonates. The present focus is on acute procedural pain; assessment of pain of longer duration remains a challenge. We therefore tested a modified version of the COMFORT-behavior scale-named COMFORTneo-for its psychometric qualities in the Neonatal Intensive Care Unit setting.
Trials 13 2012, May 23, 2012
Background: Resuscitation at birth with 100% oxygen is known to increase the oxidative burden wit... more Background: Resuscitation at birth with 100% oxygen is known to increase the oxidative burden with concomitant deleterious effects. Although fractions of inspired oxygen (FiO 2 ) < 100% are widely used in preterm infants, starting resuscitation at a (too) low FiO 2 may result in hypoxia. The objective of this study is to compare the safety and efficacy of resuscitating very preterm infants with an initial FiO 2 of 30% versus 65%.
BMC medical ethics, 2015
Although law is established on a strong presumption that persons younger than a certain age are n... more Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and ...
BMC Medical Ethics, 2015
For many decades, the debate on children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more For many decades, the debate on children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives. Although assessment of children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad. Previous research outcomes showed that children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated.
Journal of Nutrition
In neonates, bolus feeding is associated with greater rates of intestinal growth than is continuo... more In neonates, bolus feeding is associated with greater rates of intestinal growth than is continuous feeding. We tested whether the concentrations and secretion rates of trophic gut peptides are higher in bolus-fed than in continuously fed piglets. Five 21-d-old piglets were surgically implanted with gastric, arterial and portal catheters and a portal blood flow probe. At postnatal d 30 and 31, pigs received an equal amount of primed continuous or bolus feeding of a cow's milk formula in a randomized, crossover design. During a 6-h period, portal blood flow and arterial and portal concentrations of glucagon-like peptide-2 (GLP-2), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) were measured. All hormone levels were significantly increased within 1 h of the start of the experiment, independent of the feeding modality. There were no differences between bolus and continuous feeding in either the arterial concentrations or secretion rates of GLP-2, PYY and GIP. In both treatment groups, the increases in the plasma concentrations of GLP-2 and GIP after feeding were substantially greater than those for PYY. We conclude that the production or circulating concentrations of GLP-2, PYY and GIP are not significantly different in bolus-and primed continuously fed piglets. J. Nutr. 131: 729 -732, 2001.
The Journal of allergy and clinical immunology, Jan 29, 2015
Nutrition Journal, 2015
Infants undergoing cardiac surgery are at risk of a negative protein balance, due to increased pr... more Infants undergoing cardiac surgery are at risk of a negative protein balance, due to increased proteolysis in response to surgery and the cardiopulmonary bypass circuit, and limited intake. The aim of the study was to quantify the effect on protein kinetics of a short-term high-protein (HP) diet in infants following cardiac surgery. In a prospective, double-blinded, randomized trial we compared the effects of a HP (5 g · kg(-1) · d(-1)) versus normal protein (NP, 2 g · kg(-1) · d(-1)) enteral diet on protein kinetics in children &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;24 months, on day 2 following surgical repair of congenital heart disease. Valine kinetics and fractional albumin synthesis rate (FSRalb) were measured with mass spectrometry using [1-(13)C]valine infusion. The Mann-Whitney U test was used to investigate differences between group medians. Additionally, the Hodges-Lehmann procedure was used to create a confidence interval with a point estimate of median differences between groups. Twenty-eight children (median age 9 months, median weight 7 kg) participated in the study, of whom in only 20 subjects isotopic data could be used for final calculations. Due to underpowering of our study, we could not draw conclusions on the primary outcome parameters. We observed valine synthesis rate of 2.73 (range: 0.94 to 3.36) and 2.26 (1.85 to 2.73) μmol · kg(-1) · min(-1) in the HP and NP diet, respectively. The net valine balance was 0.54 (-0.73 to 1.75) and 0.24 (-0.20 to 0.63) μmol · kg(-1) · min(-1) in the HP and NP group. Between groups, there was no difference in FSRalb. We observed increased oxidation and BUN in the HP diet, compared to the NP diet, as a plausible explanation of the metabolic fate of surplus protein. It is plausible that the surplus protein in the HP group has caused the increase of valine oxidation and ureagenesis, compared to the NP group. Because too few patients had completed the study, we were unable to draw conclusions on the effect of a HP diet on protein synthesis and balance. We present our results as new hypothesis generating data. Dutch Trial Register NTR2334 .
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Papers by Johannes Van Goudoever