Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV₁), and the ratio FEV₁/FVC remained at or above the predicted normal range in all patients. FEF_25–75, FEF₅₀, and FEF₇₅ were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34 . © 1996 Wiley-Liss, Inc.     

Inhibition of estrogen-stimulated growth of uterine leiomyomas by selective estrogen receptor modulators

Uterine leiomyoma is the most frequent gynecologic neoplasm in women. By using a panel of cell lines derived from spontaneous Eker rat leiomyomas, we examined the estrogen-responsive phenotype of these tumor cells. Leiomyoma-derived ELT cell lines proliferated in response to estrogen, and estrogen-induced cell proliferation could be inhibited by the estrogen antagonist ICI 182780 and the selective estrogen-receptor modulators (SERMs) raloxifene and tamoxifen. In addition to inhibiting cell growth, these antagonists also inhibited estrogen-induced increases in progesterone-receptor expression. These data indicate that SERMs such as raloxifene and tamoxifen act as estrogen antagonists in uterine myometrial cells and suggest that this class of compounds may be effective for treatment of this important gynecologic neoplasm. © 1996 Wiley-Liss, Inc.     

Characterization of prostatic basal cell hyperplasia and neoplasia in aged macaques: Comparative pathology in human and nonhuman primates

There are very few reports of proliferative prostatic lesions occurring spontaneously in nonhuman primates. We found that 15 of 19 glands in aged macaques contained one or more epithelial lesions in the cranial lobe. These originated in the basal cell compartment and were characterized as hyperplasia and benign neoplasia. The adenomas contained variable gland formation, with morphologic and immunohistochemical evidence of secretory, mucigenous, neuroendocrine, transitional, and squamous cell differentiation. These cell types are resident in the normal prostate or appear in metaplastic lesions, and their presence in the macaque tumors is consistent with differentiation of a stem cell along multiple phenotypic pathways. The macaque growths are similar to human prostatic basal cell lesions and could provide insights into their pathogenesis as well as cellular ontogeny and general mechanisms of carcinogenesis in this organ. © 1996 Wiley-Liss, Inc.