Bronchopulmonary dysplasia of the premature baby: an immunohistochemical study.

Prematurely born infants who required assisted ventilation may develop chronic lung disease or bronchopulmonary dysplasia (BPD). The cells involved in the reparative process of the premature lung are not well defined. The repair of injured tissues is a highly standardized process and the most important cells are activated (modulated) fibroblasts (myofibroblasts). A key cytokine in controlling repair is transforming growth factor-beta (TGF-beta). To characterize the cells involved in the repair process of the premature lung, we employed immunocytochemical techniques and examined the lungs of 39 autopsied premature babies who had neonatal respiratory distress syndrome (RDS). All were treated in neonatal intensive care units and required mechanical ventilation and supplemental oxygen; all survived for at least 12 hours. Antibodies were employed against vimentin, alpha-smooth muscle (alpha-SM) actin, total muscle actin, desmin, MAC387, and TGF-beta. Our study indicates that myofibroblasts are normally present along terminal airways in the developing lung. These cells increase in number some days after lung injury, form bundles of cells encircling terminal air spaces, and acquire desmin contractile filaments shortly thereafter. Myofibroblasts do not lose their contractile filaments with time, suggesting a conversion to smooth muscle metaplasia. The proliferation and migration of such myofibroblasts at sites of lung injury is associated with the presence of TGF-beta. These findings suggest that myofibroblasts play an important role in premature lung repair. They may point the way to experimental and clinical trials that will identify drugs antagonistic to TGF-beta (or other cytokines). Such antagonists may protect the neonates who are at high risk of developing BPD.

Pulmonary pathology in surfactant-treated preterm infants with respiratory distress syndrome: an autopsy study.

The present study examines the histological features of the lungs of neonates who died of respiratory distress syndrome or related complications after surfactant therapy. Our aim was to determine whether these lungs showed any unusual histological findings. Complete autopsies were performed 6-12 h after death in 10 surfactant-treated preterm infants and in 30 infants who died before surfactant therapy was available. Representative paraffin sections of all pulmonary lobes, stained with haematoxylin and eosin, were examined microscopically. A few selected slides were also stained with periodic acid-Schiff, Vierhoff-van Gieson, and Mallory trichrome. Hyaline membrane disease and bronchopulmonary dysplasia were present in each group, although there was an increased incidence of intra-alveolar haemorrhage in surfactant-treated babies (in 8 of 10 surfactant-treated as compared with 7 of 30 untreated babies). Amongst those treated with surfactant, we observed the persistence of acute alveolar damage with unresolved hyaline membrane disease in 5 infants who died at the ages of 5, 6, 10, 12, and 13 days, respectively, and histological evidence of pneumocyte type 2 hyperplasia and dysplasia in 2 infants who died at 22 and 41 days of age, respectively. These observations reveal that surfactant-treated infants who fail to respond to therapy have continuing alveolar injury and an increased incidence of intra-alveolar haemorrhage. Since oxygen radicals can induce pneumocyte damage and necrosis and since free radicals provoke alveolar haemorrhage in animal models, we propose that the lesions we observed may stem from a lack, in some preterm babies, of specific mechanisms that detoxify oxygen radicals.

Morphological and pathogenetic aspects of proliferative vitreo-retinopathy. A histological and immunohistochemical study.

Proliferative vitreo-retinopathy (PVR) and subretinal membrane proliferation are the most common complication and cause of failure in retinal-detachment (RD) surgery. In this study, material withdrawn from 21 patients was observed. The vitreal taps of 16 bulbs affected by PVR and which had undergone vitrectomy, along with 5 bulbs obtained by enucleation, were stained with Hematoxylin Eosin and studied immunohistochemically. The cells involved in this proliferative tissue include macrophages, cellular elements of pigmented epithelium origin, fibroblasts and myofibroblasts. From the examination of enucleated bulbs, we can easily recognize that the cellular components of the membrane are represented by fibroblasts, capillaries, and occasional macrophages; meanwhile, PE cells remain at the base of the newly formed tissue.

The subretinal fluid in retinal detachment. A cytologic study.

Following retinal detachment, subretinal fluid (SRF) fills the neoformed space. Subsequently subretinal and preretinal strands of proliferative tissue begin to form. We have collected the subretinal fluid withdrawn during retinal detachment surgery. We have studied subretinal fluid cytologically to evaluate the number and the type of cells present in the fluid, and by means of transmission electron microscopy. The first cell type to be present in the fluid represented degenerated aspects of pigmented epithelial cells (PECs). Successively, other cell types appeared in the fluid as nerve cells (rods, cones and glial cells), macrophages and well preserved pigmented epithelial cells.