Objective. To verify the hypothesis that in rheu-matoid arthritis (RA), tumor necrosis factor (TNF) plays a critical role in regulating leukocyte trafficking and chemokine levels. Methods. Ten patients with longstanding RA received a single 10 mg/kg infusion of anti-TNF mono-clonal antibody (cA2). The articular localization of autologous granulocytes, separated in vitro and labeled with 111 In, was studied by analysis of gamma-camera images both before and 2 weeks after treatment. At the same sequential time points, synovial biopsy samples were assessed for infiltrating CD3 T cells, CD22 B cells, and CD68 macrophages. Synovial tissue expression of the chemokines interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), macrophage inflamma-tory protein 1 (MIP-1), MIP-1, Gro, and RANTES was also determined. Serum IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosor-bent assay. Results. Anti-TNF therapy in RA significantly reduced 111 In-labeled granulocyte migration into affected joints. There was a simultaneous and significant reduction in the numbers of infiltrating synovial CD3 T cells, CD22 B cells, and CD68 macrophages and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokines. Conclusion. TNF blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints.

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Meningococcal septic shock has a rapid onset and characteristic skin hemorrhages that allow bedside diagnosis. Initial plasma endotoxin levels are high and correlate closely with clinical outcome. In a double-blind, randomized, placebo-controlled trial (planned, n = 270; actual, n = 269), we compared the effectiveness of HA-1A (6 mg/kg of body weight iv; maximum, 100 mg), a human monoclonal antibody to endotoxin, and placebo in reducing the 28-day all-cause mortality rate among children with a presumptive clinical diagnosis of meningococcal septic shock. Treatment groups were well balanced for baseline characteristics and prespecified prognostic variables. In this trial no significant benefit of HA-1A could be demonstrated. The 28-day mortality rates in the intention-to-treat analysis were as follows: placebo, 28%; HA-1A, 18%; reduction in mortality, 33% (P = .11, per Fisher's exact test, two-tailed; odds ratio = 0.59; 95% confidence interval for the difference, 0.31-1.05). All patients tolerated HA-1A well, and no antibodies to HA-1A were detected.

In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.

The minimal inhibitory concentrations of nine antimicrobial agents was determined for over 750 clinical isolates of the Bacteroides fragilis group of anaerobic bacteria collected from nine centers in the United States during 1981. High resistance rates were documented for cefoperazone, cefotaxime, and tetracycline. Cefoxitin had the best activity of the 3-lactam antibiotics, whereas moxalactam and piperacillin had good activities. The resistance rate for clindamycin was 6%. There were no metronidazole-or chloramphenicol-resistant isolates encountered. There were significant differences in susceptibility among the various species of the B. fragilis group, particularly with moxalactam, cefoxitin, and clindamycin. Clustering of clindamycin-, piperacillin-, and cefoxitin-resistant isolates was observed at different hospitals. The variability of resistance rates with the