Karl Uy

Human Airway Contraction and Formoterol-Induced Relaxation Is Determined by Ca2+ Oscillations and Ca2+ Sensitivity

The etiology of airway hyperresponsiveness associated with asthma requires an understanding of the regulatory mechanisms mediating human airway smooth muscle cell (SMC) contraction. The objective of this study was to determine how human airway SMC contraction (induced by histamine) and relaxation (induced by formoterol) are regulated by Ca(2+) oscillations and Ca(2+) sensitivity. The responses of human small airways and their associated SMCs were studied in human lung slices cut from agarose-inflated lungs. Airway contraction was measured with phase-contrast video microscopy. Ca(2+) signaling and Ca(2+) sensitivity of airway SMCs were measured with two-photon fluorescence microscopy and Ca(2+)-permeabilized lung slices. The agonist histamine induced contraction of human small airways by stimulating both an increase in intracellular Ca(2+) concentration in the SMCs in the form of oscillatory Ca(2+) waves and an increase in Ca(2+) sensitivity. The frequency of the Ca(2+) oscillations increased with histamine concentration, and correlated with increased contraction. Formoterol induced airway relaxation at low concentrations by initially decreasing SMC Ca(2+) sensitivity. At higher concentrations, formoterol additionally slowed or inhibited the Ca(2+) oscillations of the SMCs to relax the airways. The action of formoterol was only slowly reversed. Human lung slices provide a powerful experimental assay for the investigation of small airway physiology and pharmacology. Histamine induces contraction by simultaneously increasing SMC Ca(2+) signaling and Ca(2+) sensitivity. Formoterol induces long-lasting relaxation by initially reducing the Ca(2+) sensitivity and, subsequently, the frequency of the Ca(2+) oscillations of the airway SMCs.

Pulmonary papillary adenoma a case report and review of the literature

Pulmonary papillary adenomas are rare neoplasms that predominantly occur in the periphery of the lung. We describe a 24-year-old male with a 6.0-cm spherical mass found incidentally at the periphery of the left upper lobe by imaging. Enucleation of the neoplasm was performed with intraoperative frozen section analysis. The tumor histologically showed papillary proliferations containing fibrovascular cores lined by a single layer of tumor cells that lacked atypia, mitoses, or necrosis. The histologic features were consistent with a pulmonary papillary adenoma. Pulmonary papillary adenoma was previously considered to be a benign entity. However, because of its invasive growth pattern, it has been suggested that this neoplasm has intermediate malignant potential. The clinicopathologic features and differential diagnosis of this unusual neoplasm is discussed with a review of the English literature.

Robot-Assisted Thoracoscopic Resection of a Posterior Mediastinal Mullerian Cyst

First described in 2005, the Mullerian derived cyst in the mediastinum is a rare finding with few subsequent reports. We report a case of Mullerian cyst occurring in the mediastinum of a 49-year-old female that was resected by robot-assisted thoracoscopic surgery. To our knowledge, this is the first report of robot-assisted resection of Hattoris cyst. Histopathologic analysis revealed ciliated Mullerian-type tubal epithelium positive for paired box gene 8 (PAX8), estrogen receptor (ER), and progesterone receptor (PR), confirming Mullerian differentiation. We also review the clinical presentation, pathology, and differential diagnosis of such cysts.

Lung Cancer and Mesothelioma

Keywords lung cancer, mesothelioma, non-small cell and small cell carcinomas Comments This project has been funded in whole or in part with federal funds from the Summary and Key Points 1. Tobacco is the leading cause of lung cancer. Radon exposure in the air over time is a second, but distant leading cause. Asbestos exposure, especially when combined with tobacco use, is a cause of mesothelioma. 2. The two major pathology categories of lung cancer are non-small cell lung cancer and small cell lung cancer. Common types of non-small cell lung cancers are adenocarcinoma, squamous cell and large cell carcinoma. Mesothelioma is a cancer of the pleura. 3. Treatment of lung cancer and mesothelioma requires a multidisciplinary approach to care involving Medical Oncologists, 4. The foundation for the curative treatment of early stage non-small cell lung cancer and mesothelioma is surgery. 5. The foundation for the curative treatment of early stage small cell carcinoma of the lung is combination chemoradiotherapy, although a few patients with very early small cell lung cancer may benefit from resection of the primary. 6. The goal of treatment for early stage non-small cell lung cancer and some presentations of limited stage small cell lung cancer is cure. 7. Small cell lung cancers and advanced stage non-small cell lung cancers are treated with systemic therapy (such as chemotherapy or biologic therapy). 8. Chemotherapy with or without radiation therapy is used to treat unresectable or advanced stage mesothelioma. 9. When cure is not possible, improvement in quality of life is the important goal regardless of whether there is an increase in the quantity of life gained from treatment (although sometimes, the latter is achieved).

Empyema in a Woman with Cystic Fibrosis: A Cautionary Tale

Cystic fibrosis (CF) is a disease which predisposes individuals to recurrent infective exacerbations of suppurative lung disease; however, empyema is a rare complication in these patients. Empyemas secondary to Staphylococcus aureus and Burkholderia cepacia have been described in patients with CF. We report the case of pleural empyema with mixed S. aureus and Pseudomonas aeruginosa infection in a 34-year-old woman with CF, which was managed with ultrasound-guided pigtail catheter insertion, fibrinolysis, and antibiotic therapy. Physicians should be aware of this unusual complication in CF patients, especially those receiving an immunosuppressive therapy.