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Still's disease was reported to be a type of Juvenile Rheumatoid Arthritis (JRA) by Still in 1897. Adult-onset Still's disease is an important clinical entity inducing fever, skin rash and polyarthritis. Spiking fever and rash are characteristic features for early diagnosis. Although chronic polyarthritis is similar to RA, ankylosis of hand joint is characteristic for Still's disease rather than destructive change. Increased ESR, negative autoantibodies, leukocytosis, liver dysfunction and hyperferritinemja are major laboratory findings. A markedly increased level of serum ferritin can be used, not only as an indicator of disease activity, but also as a diagnostic marker of the disease. For therapy, a moderate dose of steroid is the most effective.

Physical findings, laboratory data, treatments and prognosis were investigated in detail using 26 Japanese childhood Still's disease (CHSD) patients and 19 Japanese adult onset Still's disease (AOSD) patients as the subjects. High spiking fever and arthritis were present in all the patients. Seventy and seven percent of CHSD and 53 percent of AOSD had polyarthritis (the number of joints involved being 5 or more during the first 6 months of the disease). A comparison of the groups showed no significant difference in the initial systemic manifestations except for sore throat (CHSD: AOSD; 19%: 68%). Initial laboratory data were the same for these groups except for serum iron levels (CHSD: AOSD; 20.8 +/- 13.7 micrograms/dl: 83.0 +/- 54.2 micrograms/dl). As to joints and physical prognosis, the results were also the same for CHSD and AOSD under the similar treatment. On the basis of these data, we conclude that CHSD and AOSD are of the same disease entity so far as the present clinical features are concerned.

A 62-year-old woman, who had suffered from putsulosis palmaris et plantaris for about two years, was admitted to our hospital due to lumbago, sweating and palpitation. On the basis of physical and endocrinological examinations, she was diagnosed as Basedow's disease. X-ray findings revealed ossification in the left costo-clavicular joints, and characteristic syndesmophytes of PAO in vertebral bodies. These lesions were followed by high accumulation of 99mTc in bone scintigrams. PAO is considered to be in a category of seronegative spondylarthropathy or rheumatic disease. Previous reports of PAO accompanied with autoimmune diseases are few. The association of PAO and Basedow's disease has not been reported. As PAO in this case was refractory to conventional therapies, low-dose MTX pulse therapy(oral 7.5mg/day administration on every week) was initiated. MTX markedly improved both putsulotic palmaris et plantalis and PAO.

Increased amounts of interleukin-8 (IL-8) were detected in synovial fluids of patients with active rheumatoid arthritis (RA) by radioimmunoassay (RIA). The concentration of IL-8 correlated directly with the number of infiltrating neutrophils in synovial fluids. To elucidate the role of IL-8 in neutrophil accumulation at the site of synovitis, the in vivo effects of intraarticular injection of recombinant IL-8 (rIL-8) on leukocytes infiltration into the joint space and synovium were examined. Following a single injection of rIL-8 into the knee joint space of rabbits, redness of the joint and limp became apparent after 4 h and were associated with the rapid infiltration of neutrophilic leukocytes into the joint space and synovial tissues. These effects were time dependent, first becoming evident at 1 h and reaching a plateau in 4 h, and also dose dependent, with a minimal effect being elicited by 100 ng per joint. Although neutrophils were present in the greatest number at 4 h, subsequently mononuclear cells accumulated and became apparent in considerable number after 8 h. Synovial lining cells became ovoid, pleomorphic, and multilayered at 24 h. IL-8 had no effect on the breakdown of proteoglycan of articular cartilage. Based on these findings, IL-8 released from monocytes and synovial cells may be an important contributor to leukocyte accumulation and inflammatory events in the joints of RA.

Histopathologic studies and radiographic analysis revealed that male New Zealand black/KN (NZB/KN) mice develop degenerative polyarthritis in the joints of the forepaw and hindpaw beginning at age 2 months. Deposits of autoantibodies were observed on proliferating collagen fibers, nuclei of chondrocytes, and epidermal cells. Increases in the frequency of positivity for rheumatoid factor and anti-type II collagen antibodies and in the level of serum oxidation activity were noted in these mice. The joint disease in male NZB/KN mice was transferable to female NZB/KN mice and male BALB/c mice by intraperitoneal injection of spleen cells from the male NZB/KN mice. This animal model of arthritis will be extremely useful for analyzing not only the pathogenesis of rheumatoid arthritis, but also new strategies for its treatment, since NZB/KN mice, unlike MRL/lpr mice, do not develop severe lupus nephritis or lymph-adenopathy, and therefore have a longer survival period.

A comprehensive survey of Japanese patients with adult Still's disease was made by questionnaire which was sent to major institutions with rheumatology units in Japan. Of 146 cases from 32 institutions, 90 were judged to be definitely diagnosed as adult Still's disease. The major clinical features in these 90 patients consisted of high fever, polyarthralgia, rash, increased erythrocyte sedimentation rate, negative autoantibodies, leukocytosis, liver dysfunction, and hyperferritinemia. The incidence of several features showed significant differences between these cases and previous nonJapanese cases.

Serum erythropoietin (EPO) was measured by radioimmunoassay in 67 patients with rheumatoid arthritis (RA). Twenty of these patients judged to have iron deficiency anemia, based on reduced serum ferritin levels, had higher serum EPO levels than did the 24 other anemic patients with normal or elevated serum ferritin levels. A significant negative correlation between serum EPO and hemoglobin concentrations was noted in the former group, but not in the latter. Human recombinant erythropoietin (r-EPO) was administered to 6 anemic patients with RA, resulting in improvement of anemia in 4 patients, 2 of whom showed no change in RA activity. These findings suggest a suppressed serum EPO response ot anemia and the effectiveness of r-EPO in treating anemia associated with RA.

The mechanism(s) of anti-DNA antibody formation was comparatively investigated using in vitro human and murine B-cell culture systems. T-cell homogenate (TH) from SLE patients converted normal human B-cells to anti-DNA specific antibody-forming plasma cells (anti-DNA-SPC) when cultured with calf thymic native DNA as antigen. TH of normal human donors suppressed the formation of anti-DNA-SPC from normal human B-cell cultures even when SLE TH and DNA were added to the cultures. B-cells derived from SLE patients were insensitive to normal human TH, and resulted in the formation of many anti-DNA-SPC. TH of young and old NZB mice stimulated the formation of anti-DNA-SPC from not only NZB but also C57BL/6 murine bone marrow cultures in the presence of DNA antigen. Human and murine TH, and both B-cell cultures were reciprocally combined to test whether xenogeneic TH stimulated B-cell cultures from different species. Xenogeneic TH was effective in triggering differentiation of xenogeneic B-cells with respect to anti-DNA-SPC. The elimination of helper T-subsets (Th) resulted in the generation of fewer anti-DNA-SPC, whereas the elimination of suppressor T-subsets (Ts) caused the formation of many anti-DNA-SPC. Among organ homogenates, e.g., liver, kidney and, brain, and T-cells from old NZB mice, TH was most effective in the stimulation of anti-DNA-SPC. The effective substance was sensitive to RNase-A, but resistant to pronase and DNase-I. Phenol extracted T-cell RNA retained its activity. We concluded that the functional modulation of helper T-cells, which reflects RNA molecules, could be the main etiology of autoantibody formation against DNA by both human and murine B-cells.

An in vitro anti-NZB red blood cell (RBC) autoantibody-forming system was developed by culturing young (antiglobulin negative) or old (antiglobulin positive) NZB mouse bone marrow cells in the presence of young or old NZB thymocyte homogenates (or RNA thymus extracts) and young NZB-RBC. Using young NZB bone marrow cells, the greatest number of autoantibody forming cells were seen following stimulation with a mixture of young and old thymocyte homogenates (TH). A higher response was seen with old NZB bone marrow cells stimulated by old NZB thymocyte homogenates and RBC. Phenol-extracted thymic RNA retained activity when added to bone marrow culture containing NZB-RBC. Thymus RNA from 9 to 10 days old NZB mice had no activity although their bone marrow cells responded well to stimulation by young and old thymic RNA together with RBC. By analysing results obtained using T-cells enriched for helper and suppressor activities, we have concluded that abrogation of self-tolerance in mice is due to the appearance of functionally modulated helper T-cell subsets and to imbalance between helper and suppressor T cells.

A multicentric post-marketing surveillance study over 7 years including 5,124 patients is presented. According to clinical and laboratory data, the drug D-penicillamine was effective, with a tendency of loss of efficacy after therapy of 5 years or longer. Response was better in the early stage of the disease. Side effects were observed in 28.1% of the patients.

In a 14-day double-blind multicenter trial the efficacy and safety of piroxicam was compared with that of indomethacin among patients with extra-articular rheumatic conditions marked by cervicobrachial pain. The drugs were found to have comparable overall efficacy, with over 75% of the patients in both drug groups experiencing some improvement. Piroxicam appeared to provide somewhat better results in the subpopulation with cervicobrachial syndrome, while indomethacin was marginally better among patients with periarthritis scapulohumeralis. There was a trend toward better relief of nighttime pain with piroxicam in the cervicobrachial syndrome group at week 2. Fewer adverse reactions were observed with piroxicam, and the number of patients discontinued for side effects was also lower for piroxicam (4.1%) than for indomethacin (9.5%).

Urine of a young healthy man was added with varying amounts of mercuric chloride, incubated for 10 to 375 min, and separated into supernatant solution and precipitate by centrifugation at 105,000 X g for 60 min. Percentage of mercury amount in precipitate increased with the increase of mercury amount added. But this adsorption of mercury to urinary cells or particles could not completely account for the amount of mercury in human urine reported (Suzuki and Shishido 1975). The hypothesis that desquamation of tubular cells is a route of urinary mercury excretion in man is still sustained.

The serum oxidation activity (SOA) of patients with rheumatoid arthritis (RA) and other connective-tissue diseases (OCTD) was measured by a new colorimetric procedure the authors have devised, using o-phenylene diamine (OPD) as the indicator. A comparison was made between SOA and other clinical data, such as patient age, the particular stages of the disease and its total duration, number of joints with active synovitis, arthritic score, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), RA test results, rheumatoid arthritis haemagglutination titre (RAHA), ceruloplasmine (CP) and transferrin. Fifty-three out of 73 patients with RA (72.6%) and thirteen out of 34 patients with OCTD (38.2%) showed high levels of SOA (mean + 2SD of the control value). A significant correlation was noted between SOA and the number of joints with active synovitis, serum CP, CRP and ESR in RA patients. SOA and lipid peroxide (LP) were inversely correlated to a very significant extent. In OCTD, SOA showed a significant correlation with CP, but not with CRP or ESR. The number of active synovitis in RA patients indicated their high correlation with SOA. Drugs generally used for RA therapy, such as D-penicillamine and tiobutarit (SA96), were found to have anti-oxidant activity in the presence of RA sera. On the basis of these data, it is apparent that SOA is a reliable indicator of RA activity, and that the oxidation of various body constituents and fluids may be essential to the inflammatory processes of RA.

A multicentre double-blind comparative trial was performed in 138 patients with rheumatoid arthritis (RA) after biweekly intravenous or intramuscular injections of liposteroid (containing 2.5 mg of dexamethasone), which had been developed as a drug for targeting therapy of RA, and Decadron (containing 3.3 mg of dexamethasone) as a reference drug. The results showed a tendency to a significantly higher rate of improvement with lower frequency of side-effects in the liposteroid group than in the Decadron group. This study indicates that liposteroid is more useful for RA and that the separation of the efficacy and side-effects of steroids could be clinically confirmed to some extent.

Forty six patients (41 female and 5 male) with progressive systemic sclerosis were analysed through X-ray photographs of feet. Age ranged from 33 to 74 (mean: 48 +/- 13) years old, and durations of the disease were one to 28 (mean: 9.8 +/- 8) years. Abnormal radiological findings of feet were noted as following; bone absorption of the terminal tufts of the first phalanx (6 out of 46 cases: 13%), bone absorption of metatarsals and/or mid, basal phalanges (2 cases: 4.3%), bone erosion (6 cases: 13.0%), calcification (7 cases: 15.2%), diffuse osteoporosis (2 cases: 4.3%) and cystic lesion (one case: 2.2%). All patients with abnormal findings on X-ray photographs of feet simultaneously showed radiological changes of hands. It took 13.3 +/- 7 years until the radiological findings appeared in feet. On the other hand, it took much shorter 8.8 +/- 6 years in hands. Patients with radiological changes in feet tended simultaneously to have pulmonary and digestive tract involvements, and widespread skin lesions such identified as diffuse scleroderma. Anti-Scl 70 antibody were positive in a half of these patients.