Human synovial fibroblasts in culture have been shown to have low plasminogen activator (PA) activity; however, conditioned medium from concanavalin A‐stimulated peripheral blood mononuclear cells (c‐MCCM) stimulates the cellular levels of this protease. The present study shows that low concentrations of a series of antiinflammatory steroids inhibit the PA activities of both unstimulated and c‐MCCM‐stimulated fibroblasts. Dexamethasone, the corticosteroid studied in greatest detail, suppresses both the extracellular and cell‐associated enzyme activities; this inhibition is rapid, reversible, and is not due to the inhibition of cellular RNA, protein, or DNA synthesis. PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation. These in vitro observations suggest that physiologic and/or pharmacologic control of the PA levels in synovial fibroblasts might also be achieved in vivo by the interacting effects of mutually antagonistic agents, namely, a product from stimulated mononuclear cells and glucocorticoids.
To compare morphine dosage and effectiveness in AIDS patients with/without prior substance use and pain, a prospective, open-label case series lasting 3-18 days was conducted in both outpatients and inpatients at major pain service teaching programs. Forty-four patients, 13 with prior drug use history, who had pain associated with HIV infection or its treatment were administered sustained-release morphine (SRM) every 12 hours. The dose was titrated to pain relief for a period of > or =3 consecutive days (associated with < or =2 immediate-release morphine tablets per 24 hours), or until the patient discontinued from the study or completed 18 study days. Forty-four patients were enrolled (13 with a prior drug use history). Forty were evaluable for an intent-to-treat analgesia, including 11 with a drug use history. Twenty-four (6 users) completed this study. Former users and non-users were similar in demographics, baseline pain intensities, causes of pain, discontinuation, quality of life, and acceptability of therapy. Pain intensity decreased by > or =50% in both groups (P < or = 0.0001). To identify a stable dose, the dose of SRM more than doubled in former users and rose by 31% in non-users (mean final dose 177.4 mg and 84.9 mg, respectively) (P = 0.0018). Immediate-release morphine decreased in both; former users required more (P = 0.0006). These data suggest the utility of morphine for AIDS-related pain. Patients with a prior drug use history benefited but required substantially more morphine.
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