Identification and management of latent tuberculosis infection.

Latent tuberculosis infection (LTBI) is a condition in which a person is infected with Mycobacterium tuberculosis, but does not currently have active tuberculosis disease. An estimated 10 to 15 million persons in the United States have LTBI. Because 5 to 10 percent of persons with LTBI are at risk of progressing to active disease, identification and treatment of LTBI are essential for the elimination of tuberculosis. Screening is recommended for high-risk persons, including immigrants; residents and employees of congregate living facilities; and persons infected with human immunodeficiency virus. Targeted tuberculin skin testing remains the most acceptable method of LTBI screening. New tests are being developed, the most promising of which are in vitro interferon-gamma release assays. All screened persons found to have LTBI should be offered treatment, regardless of age. Before initiating treatment, active tuberculosis must be ruled out by patient history, physical examination, and chest radiography. The treatment of choice for LTBI is isoniazid for nine months. Hepatotoxicity is the most severe adverse effect. Isoniazid should be discontinued if transaminase levels are greater than three times the upper limit of normal in symptomatic patients or five times the upper limit of normal in asymptomatic patients.

Epidermal growth factor stimulates proton efflux from chondrocytic cells.

Proton efflux from chondrocytes alters the extracellular pH and ionic composition of cartilage, and influences the synthesis and degradation of extracellular matrix. Epidermal growth factor (EGF) promotes chondrocyte proliferation during skeletal development and accumulates in the synovial fluid in rheumatoid arthritis. The purpose of this study was to investigate the effect of EGF on proton efflux from chondrocytes. When monitored using a Cytosensor microphysiometer, EGF was found to rapidly activate proton efflux from CFK2 chondrocytic cells and rat articular chondrocytes. The actions of EGF were concentration-dependent with half-maximal effects at 0.3-0.7 ng/ml. Partial desensitization and time-dependent recovery of the response were observed following repeated exposures to EGF. EGF-induced proton efflux was dependent on extracellular glucose, and inhibitors of Na(+)/H(+) exchange (NHE) markedly attenuated the initial increase in proton efflux. The response was diminished by inhibitors of phosphatidylinositol 3-kinase and phospholipase C, but not by inhibitors of MEK (MAPK/ERK kinase) or protein kinase A or C. Thus, EGF-induced proton efflux involves glucose metabolism and NHE, and is regulated by a discrete subset of EGF-activated signaling pathways. In vivo, proton efflux induced by EGF may lead to an acidic environment, enhancing turnover of cartilage matrix during development and in rheumatoid arthritis.