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D Tibboel

Publications and source records attributed to D Tibboel.

At least 19 recordsLinked to original sources
PubMed1998

Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes.

BACKGROUND/PURPOSE: Neonates meeting criteria for extracorporeal membrane oxygenation (ECMO) often suffer from variable periods of hypoxia. During ECMO, starvation of the gut is common practice in many centres as splanchnic ischemia results in loss of intestinal integrity, which in turn predisposes for bacterial translocation and sepsis and eventually necrotizing enterocolitis (NEC) and multiorgan failure. However, minimal enteral feeding is thought to be of benefit in the critically ill. Data on intestinal integrity in newborns on ECMO and the effects of enteral nutrition are not available. This study prospectively evaluates the changes in small intestinal integrity in 16 neonatal ECMO patients. METHODS: With 2-day intervals, excretion percentages of lactulose/L-rhamnose (nonmediated diffusion), D-xylose (passive), and 3-O-methyl-D-glucose (active carrier-mediated transport) were measured by gas-liquid chromatography in a 4-hour urine sample. After obtaining baseline data in nine patients, enteral feeding was started in the next seven patients between the third and the ninth day of ECMO. RESULTS: Thirteen patients had increased lactulose/L-rhamnose ratios (>0.05) consistent with increased intestinal permeability. In three patients the lactulose/L-rhamnose ratios were within the normal range. D-xylose excretion percentages were normal (or slightly increased) in 11 patients consistent with normal (or increased) passive carrier-mediated transport. 3-O-methyl-D-glucose excretion percentages were decreased (<10%) in all but one patient, consistent with decreased active carrier-mediated transport. After introduction of enteral nutrition no significant changes of these parameters were seen. CONCLUSIONS: The authors conclude that intestinal integrity is compromised in neonates on ECMO and that introduction of enteral nutrition does not result in further deterioration. This conclusion does not support the practice of withholding enteral nutrition in critically ill newborns supported by ECMO.

3-O-Methylglucose↗
PubMed1998

Pulmonary vascular balance in congenital diaphragmatic hernia: enhanced endothelin-1 gene expression as a possible cause of pulmonary vasoconstriction.

BACKGROUND: Pulmonary hypoplasia and persistent pulmonary hypertension (PPH) are the principal causes of the ongoing mortality in congenital diaphragmatic hernia (CDH) presenting with respiratory insufficiency within 6 hours after birth. Endothelin-1 (ET-1) is an endothelial-derived vasoconstrictor, which could play an important role in modulating pulmonary vascular tone in PPH. ET-1 exerts its role in controlling vascular tone through two different subtype receptors, endothelin-A receptor (ETA) which is responsible for vasoconstriction and endothelin-B receptor (ETB) which is responsible for vasodilatation by induction of nitric oxide synthase. METHODS: We examined the pulmonary expression of ET-1, ETA and ETB mRNAs in a rat model of CDH. CDH was induced in rats by administration of 100 mg of nitrofen dissolved in olive oil on day 10 of gestation. Fetal lungs were collected after cesarean section on gestational day 22 (term) and processed for Northern blot analysis and quantitative polymerase chain reaction (PCR). RESULTS: Significantly (P<.05) enhanced levels of ET-1 mRNA were observed in CDH rats compared with control rats. In contrast to equal levels of ETB mRNA, a two- to fourfold increase in ETA mRNA levels were observed in CDH as compared with control rats. CONCLUSIONS: The upregulated expression of ET-1 and ETA receptor mRNA before birth strongly support the reason for pulmonary vasoconstriction and altered pulmonary vascular muscularization in CDH. Consequently in the clinical setting, the use of endothelin receptor blockade for the treatment of PPH may be considered against the background of the unpredictable and variable response to inhaled nitric oxide in newborns with CDH.

Animals↗
PubMed1998

Prospective evaluation of surfactant composition in bronchoalveolar lavage fluid of infants with congenital diaphragmatic hernia and of age-matched controls.

OBJECTIVES: Infants with congenital diaphragmatic hernia may have biochemically immature lungs. However, normal lecithin/sphingomyelin ratios and phosphatidylglycerol concentrations have been reported in the amniotic fluid of congenital diaphragmatic hernia patients. We hypothesized that if the lungs of congenital diaphragmatic hernia patients are surfactant deficient, that this condition would be reflected in an altered surfactant composition in the bronchoalveolar lavage fluid compared with that composition in age-matched controls. DESIGN: Prospective, controlled study. SETTING: Surgical intensive care unit in a Level III pediatric university hospital. PATIENTS: Four groups were studied: two groups of congenital diaphragmatic hernia patients (conventionally ventilated, n = 13; treated with extracorporeal membrane oxygenation, n = 5); and two control groups (conventionally ventilated, n = 13; extracorporeal membrane oxygenation, n = 6). INTERVENTIONS: Bronchoalveolar lavage, using a blind, standardized technique, was performed in conventionally ventilated congenital diaphragmatic hernia patients, extracorporeal membrane oxygenation-treated congenital diaphragmatic hernia patients, age-matched conventionally ventilated controls without pulmonary abnormalities, and extracorporeal membrane oxygenation-treated infants without congenital diaphragmatic hernia. MEASUREMENTS AND MAIN RESULTS: The concentrations of different surfactant phospholipids and the fatty acid composition of phosphatidylcholine in bronchoalveolar lavage fluid were measured. No significant differences between the concentrations of phosphatidylcholine and phosphatidylglycerol, and the lecithin/sphingomyelin ratios, were found between the four groups. The fatty acid composition of phosphatidylcholine in conventionally ventilated patients showed a median percentage of palmitic acid within the normal range for age in both groups: 68% in congenital diaphragmatic hernia patients and 73% in controls (p < .001). CONCLUSIONS: Our findings indicate that the concentrations of different phospholipids are similar in congenital diaphragmatic hernia patients and controls without congenital diaphragmatic hernia. A primary surfactant deficiency is unlikely in infants with congenital diaphragmatic hernia. However, secondary surfactant deficiency after respiratory failure may be involved.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previously reported altered distribution of CGRP-positive PNEC in full-term rats with CDH, that may lead to an imbalance in vasoactive mediators. In the present study we examined the expression of CGRP-positive PNEC during lung development in rats with CDH induced by 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen). Cesarean sections were performed on Days 16, 18, 20, or 22, and the lungs were immunostained for CGRP and immunoreactive cells were quantitated through image analysis. On Day 16, CGRP-immunoreactive staining was negative; on Day 18, CGRP-immunoreactive cells were found in all controls (not exposed to Nitrofen), whereas in CDH pups, CGRP-positive cells were present in only four of six cases. On Day 20, CGRP immunoreactivity was similar in CDH pups, Nitrofen-exposed pups without CDH, and controls. On Day 22 (term), significantly more CGRP-positive cells (i.e., number of positive cells per surface area [mm2] or lung volume [mm3]) were found in ipsilateral lungs of CDH pups than in controls (P < 0.05). The difference was even more striking in contralateral lungs of CDH pups (P < 0.001), ruling out nonspecific effects of Nitrofen. In CDH lungs, the proportion of immunostained epithelium and the size of the neuroendocrine cell clusters (neuroepithelial bodies [NEB]) were not significantly different from those of controls. On Day 22, supraoptimal dilution immunocytochemistry yielded similar results in CDH pups and controls. We conclude that in CDH, CGRP expression in PNEC and NEB is delayed during early stages of lung development. Because CGRP also exhibits growth factor-like properties for endothelium and epithelial cells, the lack of this factor during a crucial developmental stage (canalicular period) may be causally related to lung hypoplasia.

Animals↗
PubMed1997

End-results of experimental gastroschisis created by abdominal wall versus umbilical cord defect.

An experimental study was conducted to determine the end-results of two different defects on the anterior abdominal wall: an abdominal wall defect (AWD) versus an umbilical cord defect (UCD) using chick embryos. The AWD was created by leaving an intact skin bridge between the defect and the umbilical cord in group 1; the UCD was created on the umbilical cord near the junction of the skin in group 2. At the end of incubation, the intestines appeared hemorrhagic in the AWD group, but not in the UCD group. During microscopic examination, hemorrhagic areas were observed in the bowel wall and mucosal villi in the AWD group but not in the UCD group. The end-result of the defect causing the physiological umbilical hernia resulted in bowel damage resembling the classic picture of gastroschisis (GS). We conclude that the site of the defect in GS is not the abdominal wall itself, but the physiological umbilical hernia.

Abdominal Muscles↗
PubMed1997

Pulmonary expression of vascular endothelial growth factor and myosin isoforms in rats with congenital diaphragmatic hernia.

Abnormalities of the pulmonary vasculature are well documented in cases of congenital diaphragmatic hernia (CDH). Vascular endothelial growth factor (VEGF), an angiogenic factor, is a recently described endothelial cell-specific growth factor. Myosin heavy chain (MHC) isoforms such as SMemb, SM1 and SM2 are important molecular markers used to study vascular smooth muscle cell differentiation. SMemb is predominantly expressed in immature smooth muscle cells (SMC), and SM2 is expressed in mature SMCs. The authors investigated the expression of VEGF and SMC differentiation in pulmonary vessels in CDH rat lungs and in controls. The lungs of nitrofen-induced CDH rat fetuses (n = 16, gestational age 16, 18, 20, and 22 days) were stained immunohistochemically using antibodies against VEGF, SMemb and SM2, while alpha-actin was used as a general marker of vascular smooth muscle cells. In the CDH group VEGF expression was negative in pulmonary vessels before birth, and in the control group VEGF was positive in smooth muscle cells in vessel walls from 20 days both in vessels at the hilum and in pulmonary parenchyma. In both control and CDH groups, SMemb expression was positive from 16 days' gestation. SM2 expression was negative in vessel walls during the prenatal period in both groups. Alpha-actin was localized in both lungs obtained from control and CDH groups in the lung hilum from 16 days and around peripheral vessels from 18 days. Differences in vascular smooth muscle cell differentiation were not observed between control and CDH lung. These findings suggest that differences in pulmonary vascular development exist between control and CDH rats for VEGF expression, and maturational differences in smooth muscle cell differentiation are not present. This role of altered endothelial cell growth might be related to the different pulmonary vascular reactivity present in CDH lungs.

Animals↗
PubMed1997

Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia.

Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients.

Animals↗
PubMed1997

Long-term pulmonary sequelae in children with congenital diaphragmatic hernia.

Neonates with congenital diaphragmatic hernia (CDH) often suffer from respiratory insufficiency due to lung hypoplasia and pulmonary hypertension. Artificial ventilation is frequently required, and this leads to a high incidence of bronchopulmonary dysplasia. Long-term follow-up studies have shown persisting airway obstruction. To evaluate the long-term pulmonary sequelae in CDH, we studied 40 CDH patients of age 7 to 18 yr (median 11.7 yr) and 65 age-matched controls without CDH and lung hypoplasia who underwent similar neonatal treatment. Mild airway obstruction was found in both groups with more peripheral airway obstruction in CDH patients than in control subjects. Both groups had normal TLC and single-breath carbon monoxide diffusion capacity (DLCO). CDH patients had increased residual volume (RV) and RV/TLC compared with controls. Increased airway responsiveness to methacholine (MCH) was common but bronchoconstriction to inhaled metabisulfite (MBS) was rare both in CDH and control subjects. We conclude that this group of CDH patients has minor residual lung function impairment. Mild airway obstruction and increased airway responsiveness to inhaled MCH but not to MBS suggest that structural changes in distal airways are involved and not autonomic nerve dysfunction. Both artificial ventilation in the neonatal period and residual lung hypoplasia seem important determinants of persistent lung function abnormalities in CDH patients.

Adolescent↗
PubMed1997

Abnormal expression of pulmonary bombesin-like peptide immunostaining cells in infants with congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have a high neonatal mortality and morbidity owing to lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells produce bombesin-like peptide (BLP), a peptide with growth factor-like properties involved in lung development. We examined the expression of BLP immunostaining in pulmonary neuroendocrine cells (PNEC), and in clusters of these cells called neuroepithelial bodies (NEB), in the lungs of three groups of infants: patients with CDH, newborns with lung hypoplasia due to other causes, and control subjects without lung abnormalities. Morphometric analysis included: 1) percent immunostained airways; 2) percent immunostained epithelium (i.e. frequency of PNEC and NEB); and 3) NEB size. Controls and infants with lung hypoplasia did not differ with respect to BLP immunostaining. The ipsilateral and the contralateral lungs in CDH had a similar BLP immunostaining pattern of PNEC and NEB. The BLP immunostaining varied between CDH cases, possibly due to the differences in clinical presentation. The mean NEB size was significantly increased in infants with CDH compared with the other two groups (p = 0.02). Some CDH cases with large NEBs also showed a high percentage of immunostained epithelium. Lung-body weight ratio correlated positively with percent immunostained airways, and negatively with the NEB size. We conclude that in lungs of CDH patients BLP immunostaining in PNEC and NEB differs from that of infants with lung hypoplasia due to other causes and controls. The increased BLP immunostaining observed in some cases of CDH might reflect a compensatory mechanism related to impaired lung development and/or failure of neuropeptide secretion during neonatal adaptation.

Bombesin↗
PubMed1996

Prenatal diagnosis of fetal abdominal wall defects: a retrospective analysis of 44 cases.

Forty-four fetal abdominal wall defects, consisting of 31 omphalocoeles, 11 cases of gastroschisis, and two body stalk anomalies (which are excluded from further analysis), were diagnosed at 12-39 weeks (median 26 weeks) of gestation. In 10/31 (32 per cent) cases of omphalocoele and in 4/11 (36 per cent) cases of gastroschisis, multiple congenital anomalies were diagnosed. A normal amount of amniotic fluid was present in 39 cases; in three cases of omphalocoele an abnormal amount of amniotic fluid (polyhydramnios, n = 2; oligohydramnios, n = 1) was seen. Prenatally, intrauterine growth retardation (IUGR) was diagnosed in each type of anomaly only once, although the birth weight was below the tenth centile in 23 per cent of omphalocoeles and in 36 per cent of cases of gastroschisis. An abnormal prenatal karyotpye was established in 5/25 (20 per cent) cases of omphalocoele versus none in the gastroschisis group. In 36 cases an expectant obstetric management was followed, and in six cases of omphalocoele the pregnancies were terminated because of severe multiple anomalies (n = 3) or an abnormal prenatal karyotype (n = 3). The preterm delivery rate (excluding terminations) was 12/25 (48 per cent) in the omphalocoele subgroup versus 8/11 (73 per cent) in the gastroschisis subgroup. The Caesarean section rate was almost identical (19 versus 18 per cent) in both subgroups; the majority (n = 5) were performed to protect the abdominal wall defect. The overall survival rate was 39 per cent in the omphalocoele group; in all surviving infants this was the sole congenital anomaly and in each instance there was a normal karyotype. In the gastroschisis group, 8/11 (72 per cent) infants survived, of which two children also displayed unilateral hydronephrosis.

Abdominal Muscles↗
PubMed1996

The prognosis of oncologic patients in the pediatric intensive care unit.

OBJECTIVE: To evaluate the predicted mortality rate of oncologic patients in the PICU using the PRISM score and factors that might influence short-term outcomes. DESIGN: Retrospective study. SETTING: Pediatric ICU in a university hospital. PATIENTS AND METHODS: The medical charts of all oncologic patients admitted to the PICU during the period from January 1983 to December 1992 were reviewed. MAIN RESULTS: Over a period of 10 years, 51 oncologic patients were admitted on 57 occasions to the PICU. The mortality was 32%. This is significantly higher than the overall mortality in the PICU (8%). Comparison of observed and predicted mortality, derived from the PRISM score, using chi square goodness-of-fit tests showed a significantly higher observed mortality (x2(5) = 20.1, P < 0.01). Patients admitted for circulatory failure had the highest mortality (47%), followed by those with respiratory failure due to tachypnea/cyanosis (36%), central nervous system deterioration (27%), respiratory failure due to airway obstruction (25%), and metabolic disorders (20%). Of the 31 patients who needed mechanical ventilation, 17 died (55%), and when they needed inotropic support as well, the mortality increased to 69%. The mortality rose to 100% when the patient was admitted with a septic shock, necessitating mechanical ventilation and inotropic support. The median PRISM score was 5 in the survivor group and 18.5 in the non-survivor group; this difference was found to be significant using the Wilcoxon test (P = 0.01). However, some patients with high scores were found in the survivor group, as well as some with low scores in the non-survivor group. CONCLUSION: The decision to treat oncologic patients in a PICU remains difficult and has to be considered on an individual basis. However, oncologic patients do benefit from admission to the PICU. The PRISM score is not suitable for oncologic patients in the PICU, because it underestimates the observed mortality. Other factors like neutropenia, septic shock, the need for mechanical ventilation, and inotropic support should be taken into consideration.

Adolescent↗
PubMed1996

Staff attitudes towards continuation of life-support in newborns with major congenital anomalies.

UNLABELLED: This study was conducted to gain insight into the attitudes of medical staff towards life-support of newborns with life-threatening problems, seen against the background of these children's expected morbidity and quality of life. The opinions about the mode of life-support were determined by questionnaires and the demographic characteristics of the respondents were noted. Each patient's risk of mortality was scored by means of the standardized Paediatric Risk of Mortality Score (PRISM). Attitudes towards support were unanimous for 39 of the 46 patients. For the other 7 patients at least one of the respondents preferred a different support mode than that given at the time. The attitudes were influenced by the patient's risk of mortality. CONCLUSION: Decisions about life-support of newborns with life-threatening problems should include all the disciplines involved in patient care and should be made at an early stage.

Attitude of Health Personnel↗
PubMed1996

Prospective evaluation of faecal fatty acid excretion in short bowel syndrome in newborns.

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.

Fatty Acids↗
PubMed1996

Doppler ultrasound imaging: a new technique to detect lung hypoplasia before birth?

Combined color-coded Doppler and pulsed Doppler ultrasonography allows visualization of the fetal pulmonary circulation and study of pulmonary blood flow velocity waveforms. Systolic and diastolic changes were observed in fetal pulmonary artery flow velocity waveforms in a case of fetal pulmonary hypoplasia at 34 weeks of gestation. This observation supports our hypothesis that Doppler velocimetry can detect lung hypoplasia based on post- mortem examination of decreased total size of the pulmonary vascular bed, decreased number of pulmonary vessels per unit lung tissue and increased pulmonary vascular muscularization.

Adult↗
PubMed1996

Luctor et emergo.

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Fluid Therapy↗
PubMed1996

Do couples grieve differently following infant loss?

13 couples who lost an infant due to a major congenital anomaly were assessed using the Perinatal Grief Scale. Contrary to the research findings of generally less intensity of grief in men, couples did not differ significantly in this respect one-half year after the loss of their infant. On the other hand, there was no strong relationship between the scores of women and men, indicating that, apart from intensity they grieve differently.

Abnormalities, Multiple↗
PubMed1996

Embryology of congenital diaphragmatic hernia.

It is still generally believed that the defect in congenital diaphragmatic hernia results from failure of the so-called pleuroperitoneal canals (PPCs) to close at the end of the embryonic period (8th gestational week). Furthermore, it is assumed that gut could enter the thoracic cavity through this defect, causing compression and finally hypoplasia of the lung. However, this sequence of embryological events has never been studied, and many details even of normal diaphragmatic development are still unknown. Using scanning electron microscopy and a new animal model of congenital diaphragmatic hernia (CDH), the nitrofen rat model, the normal embryology of the diaphragm was reinvestigated and, for the first time, the crucial developmental steps of congenital diaphragmatic hernia formation were studied. The basic results were: (1) In normal development, the PPCs are never wide enough to allow herniation of gut loops. (2) The formation of the defect happens in an early embryonic period. (3) The early ingrowth of liver through the defect is of major importance for the formation of CDH. In another set of experiments, the nitrofen rat model of congenital diaphragmatic hernias was used to study the cellular mechanisms involved during epithelial and mesenchymal growth and differentiation in normal and in abnormal lungs. These results, combined with selected culture techniques (eg, branching morphogenesis and epithelio-mesenchymal interaction) probably open new ways to a better understanding of the mechanisms that finally lead to an abnormal lung in CDH.

Animals↗