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Biomedical subjects

D Tibboel

Publications and source records attributed to D Tibboel.

At least 55 records · Page 3Linked to original sources
PubMed2001

Restoring effects of vitamin A on surfactant synthesis in nitrofen-induced congenital diaphragmatic hernia in rats.

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Besides pulmonary hypoplasia, the pathophysiology of CDH also includes surfactant deficiency. Vitamin A (vit A) is important for various aspects of lung development. We hypothesized that antenatal treatment with vit A would stimulate lung surfactant synthesis in experimental CDH induced in rats by maternal ingestion of the herbicide nitrofen (2,4-dichloro-phenyl-p-nitrophenyl-ether) on Day 12. Fetuses were assigned to six experimental groups: (1) controls from rats that received olive oil, the vehicle; (2) fetuses from rats that received olive oil on Day 12 and vit A orally (15,000 IU) on Day 14; (3) nitrofen (N)-exposed fetuses without diaphragmatic hernia (N/no DH); (4) N/no DH from rats given vit A on Day 14; (5 ) nitrofen-exposed fetuses with DH (N/+DH); (6) N/+DH from rats given vit A on Day 14. Fetuses were delivered by C-section at Day 21. Lung DNA content was lowered in the nitrofen group as compared with the controls group, but increased by subsequent vit A treatment. Lung surfactant disaturated phosphatidylcholine was reduced in the N/+DH group and restored to control level by vit A. The expression level of surfactant proteins (SP) -A and -C was decreased in vit A-treated control rats and in nitrofen-exposed fetuses with or without DH. Vit A restored SP-A and -C mRNA expression to control levels in N/+DH. SP-B expression was lowered in N/no DH and increased by vit A in this group. The proportion of type II cells assessed by SP-B immunolabeling was lowered in N/+DH and restored by vit A treatment. We conclude that antenatal treatment with vit A restores lung maturation in nitrofen-induced hypoplastic lungs with CDH. These findings point out vit A as a potential therapeutical agent for correcting surfactant deficiency in CDH.

Analysis of Variance↗
PubMed2001

Effects of rectally administered paracetamol on infants delivered by vacuum extraction.

OBJECTIVE: To evaluate whether paracetamol (20 mg/kg rectally) relieves pain in infants delivered by vacuum extraction, and improves clinical condition. METHODS: Prospective, randomised, double-blind, placebo-controlled study. Infants delivered by vacuum extraction were randomised either to the study group (n=61) and given paracetamol or to the control group (n=61) receiving placebo. Pain assessment was performed by a validated pain score and by scoring the clinical condition. Both scores and clinical symptoms in these groups were compared with symptoms in a reference group (n=66) with uncomplicated pregnancy and delivery in vertex position without vacuum extraction. RESULTS: Pain score did not differ between groups; clinical condition in the study group improved only after the first dose. There was a significant difference (P<0.05) in objective clinical symptoms in the vacuum extraction groups, compared to the reference group. CONCLUSION: One dose of paracetamol given to neonates delivered by vacuum extraction significantly improved their clinical condition, but did not result in a significant change in objective pain scores. Subsequent doses of paracetamol did not show any effect on the clinical symptoms or appearance of the neonates studied.

Acetaminophen↗
PubMed2001

The association between physiological and behavioral pain measures in 0- to 3-year-old infants after major surgery.

To estimate the association between behavioral and physiological pain measures and to identify determinants predicting the level of association, the COMFORT 'behavior' scale, heart rate (HR), mean arterial pressure (MAP), and the variability of HR and MAP (HRV and MAPV) were assessed every 3 hours after major abdominal or thoracic surgery. Subjects were 204 infants aged 0-3 years. The within-subject correlations, using the repeated measures, were 0.37, 0.44, 0.48, and 0.49 for COMFORT 'behavior' with HRV, HR, MAP, and MAPV, respectively. Neonates had lower behavior-physiology correlations than the older infants, due to low pain scores. Pain characteristics significantly predicted the COMFORT 'behavior'-HR/MAP correlations, suggesting that the behavior-physiology correlations increase with increasing pain. The behavior-physiology correlations were not greatly affected by physical condition. These data demonstrate large interindividual differences in behavior-physiology correlations after major surgery in 0- to 3-year-old infants. These differences should be further explored in future research.

Abdomen↗
PubMed2001

Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression.

The transcription factor GATA6 is expressed in the fetal pulmonary epithelium of the developing mouse lung and loss of function studies strongly suggested that it is required for proper branching morphogenesis and epithelial differentiation. We have further investigated the role of GATA6 in this process by utilizing a pulmonary epithelium specific promoter to maintain high levels of GATA6 protein during fetal lung development. Transgenic mice expressing Gata6 cDNA under the control of the human Surfactant Protein-C (SP-C) promoter were generated and their lungs were analyzed during fetal stages. Transgenic lungs exhibit branching defects as early as embryonic day (E) 14.5 and molecular analysis just before birth (E18.5) shows a lack of distal epithelium differentiation whereas proximal epithelium is unaffected. Electron microscopic analysis and glycogen staining confirm the lack of differentiation to mature Type II cells. Thus, elevated levels of GATA6 protein affect early lung development and in analogy to other GATA factors in other tissues, GATA6 also plays a crucial role in the terminal differentiation in this case of the distal pulmonary epithelium.

Animals↗
PubMed2001

Colonization and infection by Serratia species in a paediatric surgical intensive care unit.

Serratia species are known for the infections they cause in adult and neonatal intensive care patients. Little is known about colonization and infection in paediatric intensive care patients. This study aims to describe the type of infections in critically ill newborns, infants and children, caused by Serratia spp., to compare patients colonized by Serratia spp. to patients colonized with other micro-organisms, and to assess the importance of the respiratory and digestive tracts as reservoirs. To this end, all microbiological samples taken from patients in our paediatric surgical intensive care unit between January 1986 and November 1993 were retrieved from the hospital database and patient records reviewed. Serratia spp. were isolated 1356 times from 97 patients. Eighty-five infections were diagnosed in 40 patients. Infections of the respiratory tract occurred most frequently (n= 65), followed by septicaemia (13), urinary tract infections (3), omphalitis (2), meningitis (1) and conjunctivitis (1). Colonization by Serratia spp. was associated with yearly age at admission, long ICU stay and high mortality. Both the respiratory and digestive tracts were frequently colonized. Our findings do not support the contention that the digestive tract is more important as reservoir than the respiratory tract in neonates.

Age Distribution↗
PubMed2001

Intestinal permeability in newborns with necrotizing enterocolitis and controls: Does the sugar absorption test provide guidelines for the time to (re-)introduce enteral nutrition?

BACKGROUND: In necrotizing enterocolitis (NEC), (sub)mucosal edema, hemorrhage, ulceration, or necrosis will disturb intestinal integrity, as reflected by an increased intestinal permeability. Enteral substrate is therefore withheld for a variable period up to 3 weeks (in many clinics). The authors used the sugar absorption test to measure intestinal permeability changes in surgically treated necrotizing enterocolitis patients and surgical controls to evaluate the usefulness of this test in timing the (re-)introduction of enteral feeding in NEC patients as intestinal integrity recovers. METHODS: Changes in intestinal permeability to lactulose and rhamnose were evaluated prospectively in 13 children with NEC and 10 operated control patients. The patients were given 1 mL/kg body weight lactulose/rhamnose solution at different time intervals after admission. The lactulose to rhamnose (L/R) ratio was determined by gaschromatography in 4-hour urine samples. RESULTS: The L/R ratios in NEC patients were increased for prolonged periods of time with a tendency to decrease in the third week after the start of NEC. However, in some cases, the increased L/R ratios even exceeded the 3-week period of starvation. High peaks in the L/R ratio were seen in patients suffering from bowel perforation or sepsis. Compared with necrotizing enterocolitis patients, L/R ratios of control patients were increased only in the first days after surgery and normalized more rapidly. The results of the L/R tests in this study corroborated the clinical condition of the patients. CONCLUSIONS: The sugar absorption test shows an individual variability in the recovery of intestinal permeability in a group of seriously ill newborns with advanced stages of NEC. An individual approach in restarting enteral nutrition seems to be justified; however, the optimal time-point to restart enteral nutrition cannot be determined by the sugar absorption test alone. Combining parameters of intestinal integrity and function could enable a more accurate determination of this optimal timepoint. J Pediatr Surg 36:587-592.

Capillary Permeability↗
PubMed2001

The incidence of septic complications in newborns on extracorporeal membrane oxygenation is not affected by feeding route.

PURPOSE: The aim of this study was to compare the effects of enteral and total parenteral feeding on septic complications in neonates on extracorporeal membrane oxygenation (ECMO). METHODS: Ninety-six neonates were on ECMO between January 1992 and February 1998. Matching for diagnosis and exclusion of neonates with sepsis before ECMO or undergoing surgery on ECMO left 16 enterally fed neonates (cases) and 35 parenterally fed neonates (controls) for analysis. Septic complications were scored using the criteria of the Society of Critical Care Medicine and the American College of Chest Physicians adapted to children. RESULTS: Both groups were comparable with respect to gestational age, sex, and age at initiation of ECMO. The frequency of septic complications did not differ between cases and controls: no complications, 75% versus 69%; systemic inflammatory response syndrome, 13% versus 6%; bacteremia, 6% versus 14%; sepsis, 6% versus 11%. There were no complications associated with enteral feeding. The ECMO run was significantly longer in the case group (median, 161 v. 111 hours; P =.01) and mortality rate was lower in the case group (0 v. 14%; P =.17). CONCLUSIONS: Enteral nutrition does not affect the risk of sepsis in neonates on ECMO when compared with total parenteral nutrition. Enteral nutrition is well tolerated and not associated with adverse effects.

Critical Illness↗
PubMed2001

The neonate with major malformations: experiences in a university children's hospital in the Netherlands.

Advancements in medical technology over the last decades have greatly benefited perioperative care of newborns undergoing major surgical interventions. Yet, a proportion of these babies will not survive, and doctors are forced to face the difficult ethical question of whether, in cases of severe congenital malformations or acquired diseases, the expected quality of life justifies the decision to continue, withhold, or withdraw treatment. In a tripartite approach, the authors present their relevant experiences with these newborns in the pediatric surgical department of the Sophia Children's Hospital (SCH). First the authors evaluated the mortality pattern and causes of death in surgical neonates over 2 periods (1986 through 1990 and 1996 through 2000). The mortality rate was the same, 10%. Pattern of mortality was classified into 3 groups: nonpreventable, permissible, and preventable death. The most striking difference between both mortality groups existed between the percentage of preventable deaths, 14.5% in the earlier period, versus 5% in the most recent period. Half of the preventable deaths in the former period occurred in relation to postoperative, infectious treatment complications, such as inadequate sepsis management. These errors were not seen anymore in our recent evaluation. Second, the authors studied the physical and psychosocial adjustment of former patients, particularly those operated on for digestive tract anomalies. The follow-up period encompasses from 8 to 12 years showing that the physical functioning of these children was relatively good. With respect to their cognitive and psychosocial functioning it seems justified to conclude that they are at risk for lower cognitive functioning, learning problems, and possibly lower educational levels. Third, the authors decided that ethical questions related to surgical treatment of necrotizing enterocolitis (NEC) actually fits within the scope of this article. They hypothesized that a particular minimum birth weight could be a decisive factor for refraining from surgery on ethical grounds in the treatment of this particular disease. A total of 116 patients with NEC were identified over a 5-year study period. Seventy-five fell into the lowest birth weight group (<1,500 g). The operative mortality rate (21 patients) increased with decreasing birth weight: group A, 29% (A1, 31%; A2, 26%); group B, 23%; and group C, 0%. The authors were particularly interested in the long-term follow-up of the A1 group (BW < 1,000 g), and 18 of the 30 survivors of this group were available for follow-up. There were 2 survivors with short bowel syndrome. Early assessment and neurodevelopmental outcome, at least 2 years after surgery, showed that in 14 of these 18 (78%) there were no major handicaps. The other 4 patients had one or more major handicaps (cerebral palsy, mental and/or visual handicap, and hearing loss). NEC-related mortality after surgery is highest for patients with birth weight less than 1,000 g (31%). However, in view of the overall good 2-year follow-up results of the survivors, we feel unable to define a minimum birth weight that, as such, could serve as a cutoff point for deciding to forbear, on ethical grounds, surgical treatment for NEC. The picture represented by our tripartite investigation of life and death in and after the intensive care unit period serves as a mirror and truthfully reflects ethical questions of our medical practices.

Birth Weight↗
PubMed2001

Analgesic efficacy of rectal versus oral acetaminophen in children after major craniofacial surgery.

BACKGROUND: Analgesic acetaminophen (INN, paracetamol) plasma concentrations after major surgery in neonates and infants have not yet been established in the literature. We therefore conducted a study in our intensive care unit. METHODS: Forty children, mean (standard deviation) age, 10.3 (2.3) months, received 20 mg/kg acetaminophen either orally (n = 20) or rectally (n = 20) every 6 hours after a rectal loading dose (40 mg/kg) during elective craniofacial correction. Blood samples were taken 1 hour before and 2 hours after administration of acetaminophen maintenance doses; pain scores were obtained every 3 hours. RESULTS: Acetaminophen plasma concentrations were higher in patients receiving rectal acetaminophen (mean area under the concentration-time curve [AUC], 171.2 mg x h/L) than in patients receiving oral acetaminophen (mean AUC, 111.9 mg x h/L). Pain scores were higher in patients receiving oral acetaminophen. However, after exclusion of the patients who vomited from the group receiving oral acetaminophen, acetaminophen plasma concentrations and pain scores did not differ between the groups. There was no relation between acetaminophen plasma concentrations and pain scores. Although 9 of all 40 patients (22.5%) did not reach the expected analgesic acetaminophen plasma concentrations of 10- to 20 mg/L, <7.5% of the visual analog scale pain scores exceeded 4 cm, which was considered as a cutoff point. CONCLUSION: These are the first data showing that the analgesic acetaminophen plasma concentration after major surgery in this age group does not always reach the 10 to 20 mg/L level. These data also show that, after a rectal loading dose of 40 mg/kg has been given during surgery, the best way of administering acetaminophen after craniofacial surgery is the rectal route.

Acetaminophen↗
PubMed2001

Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine.

Children aged 0-3 yr were stratified for age and randomized to receive either continuous morphine (CM, 10 microg x kg(-1) x h(-1)) with three-hourly placebo boluses or intermittent morphine (IM, 30 microg x kg(-1) every 3 h) with a placebo infusion for postoperative analgesia. Plasma concentrations of epinephrine, norepinephrine, insulin, glucose and lactate were measured before and at the end of surgery and 6, 12 and 24 h after surgery. Pain was assessed with validated pain scales [the COMFORT scale and a visual analogue scale (VAS)] with the availability of additional morphine doses. Minor differences occurred between the randomized treatment groups, the oldest IM group (aged 1-3 yr) having a higher blood glucose concentration (P=0.003), mean arterial pressure (P=0.02) and COMFORT score (P=0.02) than the CM group. In the neonates, preoperative plasma concentrations of norepinephrine (P=0.01) and lactate (P<0.001) were significantly higher, while the postoperative plasma concentrations of epinephrine were significantly lower (P<0.001) and plasma concentrations of insulin significantly higher (P<0.005) than in the older age groups. Postoperative pain scores (P<0.003) and morphine consumption (P<0.001) were significantly lower in the neonates than in the older age groups. Our results show that continuous infusion of morphine does not provide any major advantages over intermittent morphine boluses for postoperative analgesia in neonates and infants.

Age Distribution↗
PubMed2001

Extent of intestinal damage in the developing chick embryo after repetitive hypoxia under normoxic or hyperoxic conditions.

BACKGROUND: Episodes of hypoxia and reperfusion play an important role in the development of intestinal damage during perinatal development. The aim of this study was to investigate the histopathology of the intestine in the developing chick embryo after exposure to repetitive hypoxia and recovery under two different conditions: normoxic and hyperoxic (60% O2). METHODS: Chick embryos were exposed to 5 minutes of hypoxia. This was repeated six times with a recovery period of 15 minutes under normoxic conditions (21% O2) for chick embryos in test group 1 (TG1) and under hyperoxic conditions (100% O2) for chick embryos in test group 2 (TG2), from day 11 until day 20. Chick embryos that recovered under hyperoxic conditions (100% O2) were previously incubated under hyperoxic conditions (60% O2 for 24 hours). Histologic evaluation of the ileum was performed at different times after the interventions (2, 4, 8, 16, and 24 hours). RESULTS: In both test groups, only chick embryos older than 19 days showed intestinal damage. Intestinal histology on day 19 showed vasodilation of villus capillaries (10% in TG1 and 15% in TG2), necrosis in the top of the villi (29% in TG1 and 30% in TG2), and necrosis with preservation of base of the crypts (2% in TG1) and transmucosal necrosis (2% in TG2). CONCLUSIONS: Significant histologic changes, compared with the control group, were only found in chick embryos that were studied 2 hours after the interventions. Furthermore, recovery under hyperoxic conditions did not cause more intestinal damage compared with recovery under normoxic conditions.

Age Factors↗
PubMed2001

The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development.

Recent loss-of-function studies in mice show that the transcription factor GATA6 is important for visceral endoderm differentiation. It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development. The aim of this study was to determine the role of GATA6 in fetal pulmonary development. We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme. Blocking or depleting GATA6 function results in diminished branching morphogenesis both in vitro and in vivo. TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs. Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm. Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation.

Animals↗
PubMed2001

A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital.

BACKGROUND: The treatment of pediatric patients with drugs in hospitals is being impeded by a shortage in the availability of licensed drugs in an appropriate formulation. We have studied the extent of use of drugs that are not licensed for use in children (unlicensed) and drugs that are used outside the terms of the product license (off-label). We conducted this study in a Dutch academic children's hospital. METHODS: In a prospective study of 5 weeks' duration, we reviewed drug prescriptions in a pediatric ward and 3 intensive care units. We classified the prescribed drugs in 3 main categories-licensed, unlicensed, and off-label-and determined the nature of their unlicensed and off-label use. RESULTS: Two thousand one hundred thirty-nine courses of drugs were administered to 237 patients in 442 patient-days. Of 2139 prescriptions, 725 (34%) were licensed, 1024 (48%) were unlicensed, and 390 (18%) were off-label. In 392 (90%) of 435 patient-days, children received 1 or more courses of an unlicensed or off-label drug prescription in hospital. CONCLUSION: With regard to the availability of drugs of proven quality and adequate license for pediatric patients in hospital, dramatic shortcomings exist. As a result, drug legislation originally designed to protect patients and prescribing physicians against unsafe drug use and unjustified claims has turned into an insurmountable threshold to make proper drugs available for a vulnerable minority of patients.

Adolescent↗
PubMed2000

Unexpected life-threatening complications in Kabuki syndrome.

Kabuki syndrome is a rare multiple congenital anomalies/mental retardation syndrome comprising a distinct facial appearance and fetal fingertip pads. We observed two patients with Kabuki syndrome and describe unusual life-threatening complications, including stenosis of the central airways (not previously reported), extrahepatic biliary atresia, and congenital diaphragmatic hernia.

Abnormalities, Multiple↗
PubMed2000

"Gut-feeling" or evidence-based approaches in the evaluation and treatment of human short-bowel syndrome.

Short bowel syndrome is the malabsorptive state that often follows extensive resection of the small intestine. Long-term survival without parenteral nutrition depends on the process of intestinal adaptation, through which the remaining small bowel gradually increases its absorptive capacity. The process of intestinal adaptation is almost exclusively luminal nutrient dependent. To date the clinical management of short bowel patients is mostly based on a 'trial and error' regimen because human data and randomised trials using trophic substances are lacking due to the small number of patients annually present in pediatric surgical centres. We evaluate here the currently available as well as some more recently developed methods of measuring intestinal absorption and adaptation in short bowel patients. New techniques such as measurements of (1) intestinal permeability and carbohydrate absorption using the sugar absorption test, (2) gastrointestinal hormone production of gastrin, cholecystokinin and peptide YY, (3) transmural potential difference of the gastrointestinal tract using electrophysiology and (4) mucosal enzyme expression of lactase and sucrase-isomaltase using immunohistochemistry were evaluated. These new techniques are promising in monitoring the process of adaptation of the remaining intestine and evaluating the effect of therapeutic interventions in patients with short bowel syndrome.

Adaptation, Physiological↗
PubMed2000

Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia.

Pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains a major therapeutic problem. Moreover, the pathogenesis of pulmonary hypoplasia in case of CDH is controversial. In particular, little is known about early lung development in this anomaly. To investigate lung development separate from diaphragm development we used an in vitro modification of the 2, 4-dichlorophenyl-p-nitrophenylether (Nitrofen) animal model for CDH. This enabled us to investigate the direct effects of Nitrofen on early lung development and branching morphogenesis in an organotypic explant system without the influence of impaired diaphragm development. Epithelial cell differentiation of the lung explants was assessed using surfactant protein-C and Clara cell secretory protein-10 mRNA expression as markers. Furthermore, cell proliferation and apoptosis were investigated. Our results indicate that Nitrofen negatively influences branching morphogenesis of the lung. Initial lung anlage formation is not affected. In addition, epithelial cell differentiation and cell proliferation are attenuated in lungs exposed to Nitrofen. These data indicate that Nitrofen interferes with early lung development before and separate from (aberrant) diaphragm development. Therefore, we postulate the dual-hit hypothesis, which explains pulmonary hypoplasia in CDH by two insults, one affecting both lungs before diaphragm development and one affecting the ipsilateral lung after defective diaphragm development.

Animals↗