Prenatal sonographic features of spondylocostal dysostosis and diaphragmatic hernia in the first trimester.
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Spondylocostal dysostosis is a congenital disorder characterized by multiple malformations of the vertebrae and ribs. We describe the sonographic features of an affected fetus at 12 and 14 weeks of gestation. The fetus had thoracic scoliosis, multiple vertebral and rib malformations and a grossly dilated stomach that had herniated into the chest through a left-sided diaphragmatic hernia. The stomach spanned the whole length of the fetal trunk. (+info)
Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension.
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BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of 200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension. (+info)
Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats.
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Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2, 4-dichlorophenyl-p-nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12 of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before (day 10), concomitant with (day 12), or after (day 14) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A (day 10, 44%; day 12, 20%; and day 14, 40%) compared with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups (day 10, 40%; day 12, 58%; and day 14, 70%) compared with the nitrofen-treated group (16%; P < 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation. (+info)
Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia.
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Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death (day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia. (+info)
Detrimental effects of standard medical therapy in congenital diaphragmatic hernia.
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OBJECTIVE: To evaluate the impact of a nonstandard ventilation strategy on survival in congenital diaphragmatic hernia (CDH). BACKGROUND: Despite recent advances, including nitric oxide, CDH remains an unsolved problem with a mortality rate of 35% to 50%. Hyperventilation and alkalization remain common therapies. METHODS: In 1992, the authors prospectively abandoned hyperventilation and alkalization. Patients are lightly sedated and ventilated with the lowest pressure providing adequate chest movement, and the rate is set to patient comfort. Nitric oxide and extracorporeal membrane oxygenation (ECMO) are reserved for life-threatening instability. Surgical repair is delayed 1 to 5 days. Sixty consecutive patients are compared with 29 previous patients treated with hyperventilation and alkalization, 13 before and 16 after the availability of ECMO. RESULTS: Overall, 47 of 60 patients (78%) in study era 3 survived compared with 2 of 13 (15%) in the hyperventilation era and 7 of 16 (44%) in the hyperventilation/ECMO era (p < 0.0001). The disease severity and the incidence of associated anomalies did not differ between groups. To compare management strategies, patients who had treatment withheld because of lethal associated conditions were then removed from analysis. Peak inspiratory pressure and arterial pH were lower (p < 0.0001) and Paco2 was higher (p < 0.05) in era 3 than in the previous eras. The rate of pneumothorax (1.9%) decreased (p < 0.0001). In era 3, survival was 47 of 53 (89%) treated patients, and 23 of 25 inborn patients with isolated CDH survived (92%). CONCLUSIONS: Nonstandard ventilatory support of patients with CDH has led to significantly improved survival rates. This study sets a survival benchmark and strongly suggests the negative effects of hyperventilation and alkalization. (+info)
Congenital diaphragmatic hernia: ultrasonic measurement of fetal lungs to predict pulmonary hypoplasia.
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OBJECTIVE: The purpose of this study was to assess the value of biometric lung measurements for the prediction of severe fetal pulmonary hypoplasia in congenital diaphragmatic hernia and to determine whether a correlation between lung measurements and autopsy findings or neonatal outcome could be established. DESIGN: Prospective study, between 1991 and 1997. SUBJECTS: Nineteen fetuses with congenital diaphragmatic hernia. METHODS: In addition to standard biometry, sonographic measurement of the transverse thoracic diameter, sagittal thoracic diameter, fetal lung diameters at the level of the four-chamber view and lung/thoracic circumference ratio were performed. These were compared with the standard curves defined by Merz and colleagues. Autopsy examinations were performed to determine lung weight, lung weight/body weight ratio and radial alveolar count. RESULTS: Five fetuses (26%) were terminated before 24 weeks of gestation. All of these fetuses had lung measurement values below the 5th centile. Eleven of 14 fetuses (78.6%) with pulmonary hypoplasia diagnosed after 24 weeks of gestation died postnatally. The mortality rate was 70% (7/10) in the fetuses without associated anomalies. The sonographic diagnosis of fetal pulmonary hypoplasia was made in all fetuses who died postnatally. All fetuses with a lung diameter/thoracic circumference ratio below 0.09 died. Three fetuses, which had values within the normal range, survived. In contrast, measurements of the bony thorax (transverse and sagittal thoracic diameters, thoracic circumference) did not provide an indication of the presence of fetal pulmonary hypoplasia. Pulmonary hypoplasia was confirmed at autopsy in all fetuses on the basis of lung weight, lung/body weight ratio or radial alveolar count. Concomitant with pulmonary hypoplasia was polyhydramnios in ten fetuses (71.4%), mediastinal shift in 11 fetuses (78.6%), intrathoracic herniated stomach in six fetuses (42.9%) and associated malformations in four fetuses (28.6%). Postnatal mortality for these conditions was 80%, 78.6%, 100% and 100%, respectively. Postnatal mortality was 75%, 70% and 100% in the fetuses with an isolated diaphragmatic hernia. CONCLUSION: The results of this investigation suggest that the assessment of fetal lung diameter and the use of the lung diameter/thoracic circumference ratio are further useful prognostic parameters in the management of congenital diaphragmatic hernia. (+info)
Gastric volvulus in childhood.
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Gastric volvulus is an uncommon condition more so in the paediatric age group. The cause of gastric volvulus may be idiopathic or secondary to various congenital or acquired conditions. In this short series of three patients, one had volvulus which was due to ligamentous laxity and mobile spleen, second had congenital postero-lateral diaphragmatic defect and the third had hiatus hernia. (+info)
Dual-hit hypothesis explains pulmonary hypoplasia in the nitrofen model of congenital diaphragmatic hernia.
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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. (+info)