Infections and anti-TNF therapy: strategies for screening based on clinical experience.
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Biomedical subjects
Publications and source records attributed to V E Abernethy.
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We report a case of septic arthritis of an interphalangeal joint and osteomyelitis of the phalanx due toMycobacterium malmoense in a 61-year-old man with a 20 year history of rheumatoid arthritis treated with steroids and azathioprine. This was successfully treated with ethambutol, rifampicin and clarithromycin. To our knowledge this is the only reported case of septic arthritis due to this pathogen which is usually associated with respiratory disease or cervical lymphadenitis.
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We have previously shown that lysophosphatidic acid (LPA), an abundant serum lipid that binds with high affinity to albumin, is a potent survival factor for mouse proximal tubular cells and peritoneal macrophages. We show here that BSA also has potent survival activity independent of bound lipids. Delipidated BSA (dBSA) protected cells from apoptosis induced by FCS withdrawal at concentrations as low as 1% of that in FCS. dBSA did not activate phosphatidylinositol 3-kinase, implying that its survival activity occurs via a mechanism distinct from that for most cytokines. On the basis of the following evidence, we propose that dBSA inhibits apoptosis by scavenging reactive oxygen species (ROS): 1) FCS withdrawal leads to ROS accumulation that is inhibitable by dBSA; 2) during protection from apoptosis, sulfhydryl and hydroxyl groups of dBSA are oxidized; and 3) chemical blockage of free sulfhydryl groups or preoxidation of dBSA with H(2)O(2) removes its survival activity. Moreover, dBSA confers almost complete protection from cell death in a well-established model of oxidative injury (xanthine/xanthine oxidase). These results implicate albumin as a major serum survival factor. Inhibition of apoptosis by albumin occurs through at least two distinct mechanisms: carriage of LPA and scavenging of ROS.
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The use of serum antibodies to neutrophil cytoplasmic antigens (ANCA) as a diagnostic marker for Wegener's granulomatosis and other forms of vasculitis has been assessed. Although ANCA have been described by several groups the precise antigenic targets are unknown, and detection of ANCA still relies on an indirect immunofluorescence assay technique. Several different patterns of fluorescence have been produced by using sera from different groups of patients, and insufficient information is available on the frequency of positive results and of the patterns of immunofluorescence obtained when serum from patients with vasculitis as a part of a generalised connective tissue disease is used. A study was carried out on serum from 240 patients, including 23 patients with Wegener's granulomatosis, 12 with microscopic polyarteritis, and 30 with various connective tissue diseases. Three patterns of fluorescence were observed: bright coarsely granular cytoplasmic, bright non-granular cytoplasmic, and weak diffuse cytoplasmic. The bright, coarsely granular pattern was 86% specific for Wegener's granulomatosis in this series and was observed in 18 of 23 cases. Other patterns of fluorescence were found in various conditions and were not of diagnostic value. The technique is simple, inexpensive, rapid, and reproducible.