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Biomedical subjects

D Tibboel

Publications and source records attributed to D Tibboel.

At least 127 records · Page 7Linked to original sources
PubMed1993

Ablation of various regions within the avian vagal neural crest has differential effects on ganglion formation in the fore-, mid- and hindgut.

The vagal neural crest adjacent to the first seven somites gives rise to both ganglionic and ectomesenchymal derivatives. Ganglionic derivatives are the neurons and supportive cells of the enteric nervous system (ENS), cardiac, and dorsal root ganglia. Ectomesenchymal derivatives are cells in the cardiac outflow tract and the mesenchymal components of thymus and parathyroids. Ectomesenchymal derivatives are formed by a segment of the vagal neural crest, from the level of the otic vesicle down to the caudal boundary of the third somite, called the cardiac neural crest. We performed neural crest ablations to study regional differences within the avian vagal neural crest with regard to the formation of the ENS. Ablation of the entire vagal neural crest from the mid-otic vesicle down to the seventh somite plus the nodose placode resulted in the absence of ganglia in the midgut (jejunum and ileum) and hindgut (colon). The foregut (esophagus, proventriculus, gizzard, and duodenum) was normally innervated. After ablation of the vagal neural crest adjacent to somites 3-5, ganglia were absent in the hindgut. Ablations of vagal neural crest not including this segment had no effect on the formation of the ENS. We surmise that the innervation of the hindgut in vivo depends specifically on the neural crest adjacent to somites 3-5, whereas innervation of the midgut can be accomplished by all segments within the vagal neural crest. The foregut can also be innervated by a source outside the vagal neural crest. To study intrinsic differences between various vagal neural crest segments regarding ENS formation, we performed chorioallantoic membrane cocultures of segments of quail vagal neural anlage and E4 chicken hindgut. We found that all vagal neural crest segments were able to give rise to enteric ganglia in the hindgut. When the neural crest of somites 6 and 7 was included in the segment, we also found melanocytes in the hindgut, suggesting that this segment is more related to trunk neural crest. Furthermore, we found that the vagal neural anlage from older embryos (> 18 somites) showed an increased potential to form enteric ganglia. This suggests that vagal neural crest cells that have been in prolonged contact with the neural tube in vivo, because of either late emigration or delayed migration, have an increased probability to form enteric ganglia.

Animals↗
PubMed1993

Radiographic evidence of bronchopulmonary dysplasia in high-risk congenital diaphragmatic hernia survivors.

Congenital diaphragmatic hernia is a congenital malformation associated with pulmonary hypoplasia. It often leads to respiratory failure, requiring artificial ventilation with high inflation pressures and high percentages of oxygen. We evaluated radiographic evidence of bronchopulmonary dysplasia (BPD) in survivors, who presented with respiratory distress within 6 hours after birth, by a radiographic scoring system measuring the severity of BPD by the Toce score and the degree of pulmonary hypoplasia by the Touloukian score. Fifteen of 45 survivors (33 percent) had clinical and radiological lung disease resembling BPD. As a group they had significantly higher Touloukian and Toce scores than survivors without BPD. Morbidity expressed as the duration of artificial ventilation, supplemental oxygen, and hospital stay was much higher in the BPD group. The hypoplastic lung in infants with congenital diaphragmatic hernia appears to be as susceptible to barotrauma and pulmonary oxygen toxicity as the lungs of prematurely born infants. To what extent BPD occurring in congenital diaphragmatic hernia survivors might influence the future development of lung function is not yet known.

Bronchopulmonary Dysplasia↗
PubMed1993

The distribution and characterization of HNK-1 antigens in the developing avian heart.

The heart originates from splanchnic mesoderm and to a lesser extent from neural crest cells. The HNK-1 monoclonal antibody is a marker for early migrating neural crest cells, but reacts also with structures which are not derived from the neural crest. We investigated whether heart structures are HNK-1 positive before neural crest cells colonize these target tissues. To that end, we determined the HNK-1 antigen expression in the developing avian heart on immunohistochemical sections and on Western blots. The HNK-1 immunoreactivity in the developing chick heart is compared with data from literature on the localization of neural crest cells in chick/quail chimeras. Structures with neural crest contribution, including parts of the early outflow tract and the related endocardial cushions, the primordia of the semilunar valve leaflets and the aorticopulmonary septum were HNK-1 positive. Furthermore, other structures were HNK-1 positive, such as the atrioventricular cushions, the wall of the sinus venosus at stage HH 15 through 21, parts of the endocardium at E3, parts of the myocardium at E6, and the extracellular matrix in the myocardial base of the semilunar valves at E14. HNK-1 expression was particularly observed in morphologically dynamic regions such as the developing valves, the outflow tract cushion, the developing conduction system and the autonomic nervous system of the heart. We observed that atrioventricular endocardial cushions are HNK-1 positive. We conclude that: a HNK-1 immunoreactivity does not always coincide with the presence of neural crest cells or their derivatives; (2) the outflow tract cushions and atrioventricular endocardial cushions are HNK-1 positive before neural crest cells are expected (stage HH 19) to enter the endocardial cushions of the outflow tract; (3) the observed spatio-temporal HNK-1 patterns observed in the developing heart correspond with various HNK-1 antigens. Apart from a constant pattern of HNK-1 antigens during development, stage-dependent HNK-1 antigens were also found.

Animals↗
PubMed1993

Withholding and withdrawal of life support from surgical neonates with life-threatening congenital anomalies.

We evaluated why and how life support was withheld or withdrawn in surgical neonates. During the study period, January 1988 through December 1991, 529 neonates were admitted, 52 of whom died (10%). Twenty-eight deaths were due to the underlying disease. The other 24 patients died because treatment was withheld or withdrawn. In 15 of 24 (group A, mean stay 9.2 +/- 9.1 days) treatment was initially started but later withdrawn (13/15) because of the severity of congenital anomalies alone (7/12) or congenital anomalies associated with chromosomal anomalies (5/12). In 9 of 24 (group B, mean stay 20.3 +/- 17.3 days) treatment was withdrawn because of serious complications. In all cases often lengthy discussions have led the doctors and nurses together with the parents to chose unanimously for withdrawal of treatment. Mechanical ventilation was the intervention most frequently withdrawn (10/15 group A, 9/9 group B). Vasoactive and other drugs were withheld in 5 patients of group A. Sedatives and analgetics were administrated as supportive care permitting the child to die in a humane way, 17 in the lap of a parent and 7 in the lap of a nurse. We conclude that life-sustaining care is withheld or withdrawn relatively frequently from patients at our ICU. Such decisions are ethical ones, taken in the light of professional and technical expertise. Evaluation of withholding or withdrawal of treatment is difficult but necessary to evolve appropriate decision-making procedures and to formulate humane standards of intensive care.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1993

The natural history of congenital diaphragmatic hernia and pulmonary hypoplasia in the embryo.

Up to now, descriptions of the natural history of congenital diaphragmatic hernia (CDH) associated with pulmonary hypoplasia (PH) are based exclusively on observations made in the fetal period. However, nothing is known about the events that take place in an embryo with CDH. Recently, an animal model of CDH and PH has been established in rat embryos to study the embryology and natural history of this lesion. We exposed 36 pregnant Sprague-Dawley rats to a single dose of 100 mg nitrofen on day 11 of pregnancy. A total of 356 staged embryos and fetuses from day 13 to day 21 were studied by light and scanning electronmicroscopy. The litters of 9 untreated rats (124 normal age-matched embryos and fetuses) served as controls. The abnormal development of the diaphragmatic anlage was first seen in embryos aged 13 to 14 days. A defect appeared in the dorsal part of the diaphragm, normally on the right side. The liver grew through this defect early on. Gut was found in an intrathoracic position only in the very late stages (day 21/22) and newborns. Compared to controls, lungs of nitrofen-embryos with CDH were smaller, depending on the size of liver found in the thoracic cavity. Histologically, compression of lung was absent at these stages. Most authors speculate that CDH results because the pleuroperitoneal canals fail to close at the end of the embryonic period (ie, week 8 to 10 in human development) leading to a defect in the dorsolateral region of the diaphragm. However, contradictory to this assumption, our findings indicate that diaphragmatic defects develop in early embryonic life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Persistent pulmonary hypertension in high-risk congenital diaphragmatic hernia patients: incidence and vasodilator therapy.

Survival of congenital diaphragmatic hernia patients depends on the gravity of pulmonary hypoplasia and persistent pulmonary hypertension (PPH). Many vasoactive drugs have been used in the treatment of PPH, but often they also lower peripheral resistance, leading to a significant drop in arterial blood pressure. The incidence of PPH in 52 high-risk diaphragmatic hernia patients and the results of treatment with tolazoline and prostacyclin were evaluated in a study lasting 52 months and involving 52 patients. High-risk patients require ventilatory support within 6 hours after birth. Study parameters were alveolar-arterial oxygenation difference (AaDO2), oxygenation index (OI), and mean arterial blood pressure (MABP), measured at set times before and after administration of tolazoline or prostacyclin. Twenty-one patients had documented episodes of PPH (46%), and 18 of them died. Tolazoline did not lower AaDO2 and OI values, but MABP dropped significantly. Prostacyclin caused a significant decrease of AaDO2 and OI values without an effect on MABP. We concluded: (1) PPH presented in 46% of our patients, associated with a high mortality rate; (2) tolazoline is not an effective dilator of the pulmonary vascular bed and lowers MABP; and (3) prostacyclin is an effective pulmonary vasodilator as reflected by ventilation parameters without systemic side effects; it does not affect overall outcome but can used as a "bridge" to extracorporeal membrane oxygenation.

Blood Pressure↗
PubMed1993

Postoperative care after craniofacial surgery: evaluation of routine laboratory testing.

In this study, two protocols for monitoring children after major craniofacial surgery were compared. The first protocol consisted of repetitive laboratory testing in 37 children to detect surgical and medical complications during a 2-year period. None of the complications were predicted by abnormal test results, and abnormal results of routinely performed tests never led to a change in management. The second protocol, an adapted version of the first protocol, was continued for 5 years as a prospective study in 98 children: Patients were routinely tested only once, and further testing was initiated either after an abnormal test result or because of clinical symptoms. Clinical management and the incidence of postoperative complications did not differ between groups. The second protocol considerably reduced the mean number of tests per patient from 42.5 to 7.0, but in contrast with the first protocol, 84 percent of abnormal test results led to changes in clinical management. In conclusion, in the first group the test results were not used and were not predictive of complications. In the second group, tests were more apt to have abnormal results and often initiated treatment. This shows that indiscriminate routine laboratory testing is of limited value in covering the postoperative period after craniofacial surgery.

Child↗
PubMed1993

Regional differences between various axial segments of the avian neural crest regarding the formation of enteric ganglia.

The vagal neural crest adjacent to somites 1-7 gives rise to the enteric ganglia along the entire digestive tract. It is generally assumed that formation of enteric ganglia in preumbilical gut is independent of the axial segment from which the neural crest originates. In post-umbilical gut, however, there is evidence that the axial segment of origin of the neural crest might be relevant to neural differentiation. In this part of the gut, we previously identified a subpopulation of HNK-1-immunoreactive cells within the enteric mesenchyme. This immunoreactivity disappeared upon formation of the enteric nervous system. We studied the interaction between various axial segments of quail neural crest and the microenvironment in a neural chicken hindgut using chorioallantoic membrane cocultures. We found that neural crest cells from various axial segments could migrate into the gut and home to the correct sites. However, whereas vagal neural crest cells differentiated into enteric neurons, neural crest cells from truncal segments mainly differentiated into melanocytes. The HNK-1-immunoreactivity within the enteric mesenchyme only disappeared when neural crest cell colonization was followed by differentiation into enteric neurons and subsequent formation of enteric ganglia. To determine whether differentiation of neural crest cells in chorioallantoic membrane cocultures was influenced by the prolonged presence of the neural tube and notochord, we developed a new coculture system, using neural crest cells cultured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Avoidance of emergency surgery in newborn infants with trisomy 18.

Trisomy 18 (Edwards' syndrome) presents with characteristic external features as well as life-threatening abnormalities; many of these abnormalities require surgical correction during the neonatal period. Children with trisomy 18 have a very short life expectancy, and all long-term survivors have severe mental retardation. Difficult medical and ethical issues arise over whether or not to institute treatment when a newborn infant with suspected trisomy 18 has a life-threatening anomaly. We studied the policy of treatment in seven patients with clinical Edwards' syndrome. For three, the period of uncertainty was shortened because trisomy 18 was rapidly diagnosed by karyotyping of a bone-marrow aspirate. Four of the patients underwent surgery before the diagnosis of trisomy 18 was confirmed by routine karyotyping in lymphocytes; karyotyping in bone marrow might have allowed invasive treatment to be avoided in three of these. Rapid confirmation of clinically suspected Edwards' syndrome is very important because surgery may then be withheld. A newborn infant with trisomy 18 should be considered as a patient with a hopeless outlook who ought not to be subjected to invasive procedures. The decision to withdraw or withhold treatment should be discussed frankly with the parents. The period of uncertainty can be reduced to a minimum by the use of karyotyping in bone marrow.

Abnormalities, Multiple↗
PubMed1992

Cardiopulmonary resuscitation in paediatric intensive care patients.

To identify the success of cardiopulmonary resuscitation in the paediatric ICU patient we undertook a retrospective study in an 11-bed medical and a 14-bed surgical paediatric ICU over a 32-month period. Thirty-four patients suffered an arrest in the ICU. Only 4 patients could be resuscitated successfully; 1 died after 24 h. Of the 3 long-term survivors 1 suffered from severe neurologic sequelae. All patients were in CCS classes III or IV. All but 3 patients had PSI scores greater than 8. The decision to resuscitate or to withhold therapy in individual patients who are deteriorating in the course of a critical, preceding illness should not be based on the risk index of these scoring systems. Both medical and ethical considerations should be guidelines in the process of decision-making.

Adolescent↗
PubMed1992

Colonization characteristics of enteric neural crest cells: embryological aspects of Hirschsprung's disease.

This study explores the development of the enteric nervous system in avian embryos. Particular emphasis was given to colonization characteristics of neural crest cells present in primitive enteric ganglia. By coculturing neuronal and aneuronal gut of quail and chicken embryos, we investigated if and when neural crest cells in primitive enteric ganglia could detach from these ganglia, migrate, and colonize adjacent chicken gut. Quail neural crest cells were identified using the quail nucleolar marker and the HNK-1 antibody. Enteric neurons were identified using three monoclonal antibodies directed against neurofilament proteins. We found that neural crest cells detached from primitive ganglia in neuronal quail gut from E6 till E9, whereas neural crest cells did not leave enteric ganglia from E10 gut. These observations show that there is a transient phase during which enteric neural crest cells can leave the gut. To determine whether neural crest cells could colonize neuronal gut we cocultured neuronal gut or the neural primordium and neuronal chicken gut (E11). We found that quail neural crest cells do not colonize neuronal E11 gut, whereas they do colonize aneuronal gut of the same age. We suggest that aneuronal gut attracts neural crest cells by diffusing factors.

Animals↗
PubMed1992

Differences in phosphorylation state of neurofilament proteins in ganglionic and aganglionic bowel segments of children with Hirschsprung's disease.

Hirschsprung's disease is characterized by the absence of enteric neurons in the myenteric and submucosal plexus and the presence of many unmyelinated axons, visible in ganglion like structures, in the aganglionic part of the bowel. In previous studies we showed that the immunoreactivity of a monoclonal antibody (2F11) specific for neurofilament proteins is increased in aganglionic bowel segments. We now investigated whether the increased neurofilament protein staining results from an increase in neurofilament protein immunoreactivity in the aganglionic segment or if it is also related to differences in the phosphorylation state of neurofilament proteins. Bowel resection specimens of patients with Hirschsprung's disease and control patients were investigated by immunohistochemical techniques using a panel of different monoclonal antibodies that are specific for neurofilament proteins and have well known reaction patterns against different phosphorylated epitopes present on two neurofilament proteins, the middle (NF-M) and the high (NF-H) molecular weight subunit. For comparison the specimens were also stained for acetylcholinesterase, neuron-specific enolase (NSE), S-100, and glial fibrillary acidic protein (GFAP). Immunostaining with this panel of antineurofilament-antibodies showed differences in the phosphorylation state of neurofilament proteins in the aganglionic and the ganglionic bowel segments of patients with Hirschsprung's disease. These changes involved the phosphorylation state of these proteins and the ratio of NF-H and NF-M in neurofilament proteins. Staining with NSE and S-100 showed no significant differences between Hirschsprung's disease patients and control patients. We surmise that during the ingrowth and differentiation of hypertrophic axons the composition of neurofilament proteins formed in the aganglionic bowel segment differs from the neurofilament proteins formed in the ganglionic and control bowel segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats.

In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs.

Animals↗
PubMed1992

Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities.

We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.

Animals↗