A B S T R A C T A study of sera from 285 patients with definite or classical rheumatoid arthritis (including 37 patients receiving no anti-inflammatory drugs) and sera from 67 healthy subjects has confirmed 10 published reports of a statistically significant decreased blood histidine concentration in patients with rheumatoid arthritis. Contrastingly, in sera from 231 patients with a variety of acute and chronic illnesses other than rheumatoid arthritis, no statistically significant hypohistidinemia was observed either in the group as a whole or in association with the administration of aspirin, prednisone, indomethacin, phenylbutazone, or dextropropoxyphene.In the patients with rheumatoid arthritis there was a statistically significant correlation between the serum histidine concentration and the following: Westergren sedimentation rate (r = -0.33, P < 10-'), grip strength (r = 0.26, P < 10'), hematocrit (r= 0.23, P < 10-'), duration of morning stiffness (r =-0.14, P = 10-'), walking time (r = -0.13, P = 10"), latex titer of rheumatoid factor (r = -0.11, P = 0.001), and the duration of arthritis (r = -0.06, P = 0.05). There was no statistically significant association between the serum histidine concentration and the duration of rheumatoid arthritis in the 151 patients with disease of 0-10-yr duration (r = 0.02, P = 0.5), the sex of the patient, or the presence of antinuclear antibody (r = 0.007, P = 0.9). The serum histidine concentration was less in rheumatoid patients receiving steroids (P = 0.00001), gold (P = 0.009), and aspirin (P = 0.15) than in rheumatoid patients not receiving these drugs.

Treatment of hyperuricemic patients with allopurinol over an average of 3.4 years resulted in a significant improvement of kidney function in this male cohort from the Veterans Administration Healthcare System. Clinicians should consider this potential benefit of allopurinol in the treatment of patients with hyperuricemia, those with overall maintained renal function.

Gold thiomalate (40 pM), penicillamine (40 pM), and histidine (20 pM) inhibit the copper-catalyzed (20 pM) thermal aggregation of human gamma globulin (0.8 mg/ml). At these concentrations, inhibition of gamma globulin aggregation was 87%, 96%, and 99% complete. This effect may be related to the reported suppressive effect of these agents in rheumatoid arthritis and adds support to the hypothesis that the hypohistidinemia of rheumatoid arthritis participates in the pathogenesis of the disease. Gold thiomalate (l), D-penicillamine (2),and L-histidine (3,4) have been reported to be effective in the treatment of rheumatoid arthritis. There is good evidence that aggregated gamma globulin is inflammatory, antigenic, and a stimulus to the formation of rheumatoid factors (5). There is also some evidence for the presence of aggregated gamma globulin in the synovial fluid of patients with rheumatoid arthritis (6,7).