Six of 9 patients with previously documented adverse reactions to allopurinol exhibited transformation of their peripheral blood lymphocytes when these were exposed in vitro to the allopurinol metabolite, oxypurinol. In 2 of these subjects, intradermal skin challenge was positive at 48 hours with either allopurino1 or oxypurinol. The evidence presented suggests that some adverse reactions to allopurinol represent delayedtype hypersensitivity to oxypurinol.

Ross River virus has been incriminated in the etiology of many sporadic and epidemic cases of polyarthritis in Australia and the Pacific. Both synovium and synovial exudate fluid recovered from the knee of an epidemic polyarthritis patient showed a predominantly mononuclear leucocyte infiltrate. Infectious virus could not be recovered from the synovial exudate. Functional natural killer cells were detected in the synovial fluid. Their level of cytotoxic activity was similar to that detected in the peripheral circulation.

The thiol status of patients with rheumatoid arthritis is significantly different from that of controls. Plasma thiol levels are lower, albumin thiol reactivity is altered and intracellular thiol levels measured after hemoglobin precipitation are increased. These variations correlate with other indices of disease severity and are one measure of a disturbance in the degree of oxidation of the blood. Penicillamine, in common with other effective therapeutic agents, produces an increase in serum thiol concentration. It causes a greater effect on serum thiol reactivity than other drugs and in particular it increases 'fast reacting' thiol levels without significantly altering the 'slow reacting' thiol level.

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SUMMARY'Spontaneous' lymphoblastoid cell lines (LCL) were established from patients with either rheumatoid arthritis (RA) or infectious mononucleosis (IM) or from healthy donors. Differences in Epstein-Barr virus (EBV) strains were determined by measuring the mol. wt. and expression of viral antigens in each of the LCLs. In addition to the previously reported EBV nuclear antigens, the LCLs also contained EBV-induced antigens with tool. wt. of 48K and 58K which were present in all but two of the lines. One of the differences observed between each of the groups of cell lines was their ability to produce viral antigens. Early and late antigens were identified by immunoblotting in most of the RA lines, two of the normal lines but none of the cell lines from patients with IM. Many of the IM cell lines were also found to express multiple EBNA1 antigens. The results demonstrate that a variety of wild-type EBV strains exist. However, the similarities observed in a number of the lines suggest that the diversity of strains may be limited.

The incidence of antibodies to Epstein-Barr nuclear antigen type 2 (EBNA-2) was determined in sera from rheumatoid arthritis (RA) patients and control subjects, by protein immunoblotting. Sixty-eight percent of the RA patients and 48% of the controls possessed anti-EBNA-2 antibodies. The titer of anti-rheumatoid arthritis nuclear antigen (RANA) in RA patient sera showed a stronger correlation with serum reactions to EBNA-2 than with reactions to EBNA-1. Our results indicate that the presence of EBNA-2 may make a major contribution to the RANA reaction.

Clinically euthyroid patients on long term maintenance therapy with the non-steroidal anti-inflammatory drug fenclofenac (Flenac) show an unusual and abnormal pattern of serum thyroid function tests. In all twelve patients studied, total T4 concentrations were grossly subnormal (mean 28.4 +/- 9.9 (SD) nmol/l and total T3 levels low-normal (mean 1.4 +/- 0.3 (SD) nmol/l), whereas rT3 (mean 0.36 +/- 0.06 (SD) nmol/l) and basal TSH levels (mean 1.9 +/- 0.5 (SD) mu/l) were within their respective normal ranges. Free T4 levels were low normal (mean 11.0 +/- 1.0 (SD) pmol/l) while TSH, T4 and T3 responses to intravenous TRH were similar to those found in euthyroid subjects. These effects appear to be due predominantly to in vivo inhibition of binding of thyroid hormones to carrier proteins in serum, rather than in vitro drug interference in the radioimmunoassays employed. Fenclofenac does, however, interfere in those laboratory methods employing serum proteins as binding agents. Thus the Thyopac 4 method for serum total T4 grossly over-estimates T4 levels, while thyroid hormone binding capacity (Thyopac 3) is low. Since fenclofenac is one of the most potent drugs interfering with routine indices of thyroid status, it is suggested that suspected thyroid dysfunction is excluded before commencing therapy with the drug.

Using the protein immunoblot technique, antibodies to an Epstein-Barr virus-induced 92 kD polypeptide (EBNA-2) were more frequently present in the sera of patients with rheumatoid arthritis and their consanguineous relatives when compared with a control group. No association of anti-EBNA-2 antibody with the HLA-DR antigens was observed.