Clinical and Molecular Aspects of Stress on the Developing Lungs (Doctoral Thesis)

1999-11-25T00:00:00Z

Growth and development are nmdamental processes and understanding of the mechanisms resulting in abnonnal growth and development fonn the core of pediatrics and pediatric surgery. ivIany acute problems in the perinatal period mise from premahlrity and congenital anomalies. AWlOugh mOltality is steadily decreasing due to progress in h'cahnent modalities and prenatal diagnosis, remaining life-long morbidity is increasingly impOltanL hI many of these children such as premahu'e newboms witll respiratOlY dish'ess syndrome (ROS), abnOlmal pulmonary development in case of congenital diapluagmatic hemia (CDR) or oligohydrarmuos associated with prolonged mphlre of membrarles arId renal anomalies (the so called Potter sequence) the lungs are the tar'get orgarl for treatment.

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension (Article)

1999-01-01T00:00:00Z

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.

Okazaki, T.

Clinical and Molecular Aspects of Stress on the Developing Lungs (Doctoral Thesis)

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension (Article)