No abstract

Tumor necrosis factor alpha (TNF-ox) is a key mediator of inflammation and may promote human immunodeficiency virus replication in latently infected cells. Since cryptococcosis often is associated with aberrations in the host inflammatory response and occurs preferentially in persons with AIDS, we defined the conditions under which human leukocytes produce TNF-a when stimulated by Cryptococcus neoformans. Peripheral blood mononuclear cells (PBMC) produced comparable amounts of TNF-ot following stimulation with C. neofonnans and lipopolysaccharide. Detectable TNF-ot release in response to C. neoformans occurred only when fungi with small-sized capsules were used and complement-sufficient serum was added. Fractionation of PBMC established that monocytes were the predominant source of TNF-ot. TNF-a gene expression and release occurred significantly later in PBMC stimulated with C. neoformans than in PBMC stimulated with LPS. C. neoformans was also a potent inducer of TNF-o from freshly isolated bronchoalveolar macrophages (BAM). Upon in vitro culture, BAM and monocytes bound greater numbers of fungal cells, yet their capacity to produce TNF-a following cryptococcal stimulation declined by 74 to 100%. However, this decline was reversed if the BAM and monocytes were cultured with gamma interferon. These data establish that C. neoformans can potently stimulate TNF-ox release from human leukocytes. However, several variables profoundly affected the amount of TNF-a released, including the type of leukocyte and its state of activation, the size of the cryptococcal capsule, and the availability of opsonins.

It is estimated that 5-14% of patients presenting with hemoptysis will have life-threatening hemoptysis, with a reported mortality rate between 9 and 38%. This manuscript provides a comprehensive literature review on lifethreatening hemoptysis, including the etiology and mechanisms, initial stabilization, and management of patients. There is no consensus on the optimal diagnostic approach to life-threatening hemoptysis, so we present a practical approach to utilizing chest radiography, computed tomography, and bronchoscopy, alone or in combination, to localize the bleeding site depending on patient stability. The role of angiography and embolization as well as bronchoscopic and surgical techniques for the management of life-threatening hemoptysis is reviewed. Through case presentation and flow diagram, an overview is provided on how to systematically evaluate and treat the bronchial arteries, which are responsible for hemoptysis in 90% of cases. Treatment options for recurrent hemoptysis and definitive management are discussed, highlighting the role of bronchial artery embolization for recurrent hemoptysis.