Predicting factors for severity of rheumatoid arthritis: a prospective multicenter cohort study of 172 patients over 3 years.

Rheumatoid arthritis may take an unfavourable course leading to rapid functional decline in a certain percentage of patients. Early identification of these patients is desirable. The aim of this study was to evaluate clinical and laboratory parameters for their value in the prediction of bad outcome. A total of 172 patients with early arthritis were followed for 3 years. Higher initial values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum concentration of cartilage oligomeric matrix protein, Health Assessment Questionnaire score, Larsen score of feet, disease activity score, and swollen and tender joint count predicted worse outcome. An association with the presence of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be established. We conclude that prognosis in an individual with rheumatoid arthritis depends on many factors. The determination of independent prognostic factors for progression of rheumatoid arthritis is a valuable tool in early arthritis to select patients for more aggressive therapy.

Benzimidazole-type glycine antagonists: the role of the ring nitrogen atoms.

Several derivatives of 1H-benzimidazole-2-carboxylic acid (BICA, 2a) were tested in vitro in comparison to 1H-indole-2-carboxylic acid (ICA, 1e) for their ability to displace [3H]glycine from rat hippocampal membranes. Compound 2a was 8 times more potent than 1e (Ki 5.3 microM, as compared to 42 microM). However, introduction of a carboxymethyl group or a corresponding ester at position 3 had no positive effect on the potency of 2a, while this type of structural modification increased the potency of 1e significantly. Nevertheless, 1-carboxymethyl-BICA (2b) displaced [3H]glycine with similar potency as the corresponding 3-carboxymethyl-ICA 1c, indicating that also a nitrogen atom lacking a hydrogen atom can be engaged in glycine receptor interaction. N-Methylation strongly reduced the potencies of both BICA and ICA derivatives.

Interaction of long chain n-alkyl diamines with the NMDA receptor complex.

Long chain 1, omega-diamines with 8, 10, 12, 14 and 16 carbon atoms reduced the binding of [3H]MK 801 to rat hippocampal membranes with IC50 values of 333, 72, 16.5, 4.7 and 4.3 microM, respectively. In the presence of medium-effective concentrations of the diamines, the concentration response curve of the stimulation by the polyamine spermine was shifted to higher spermine concentrations, reaching similar maximal stimulation as in the absence of the diamines. In the case of 1,12-diaminododecane (N-12-N) and 1,14-diaminotetradecane (N-14-N), the extent of this shift was compatible with competitive antagonism of spermine. Inhibition of [3H]MK 801 binding by long chain diamines was sensitive to spermine, inhibition by N-12-N and N-14-N exhibited the highest sensitivities. Of all diamines tested, N-12-N and N-14-N seem to be the most likely candidates for inverse polyamine agonists.

[High dosage vitamin E therapy in patients with activated arthrosis]. / Hochdosierte Vitamin-E-Therapie bei Patienten mit aktivierter Arthrose.

The known antiphlogistic in vitro effect of vitamin E was tested in a double-blind randomized study in patients with osteoarthritis. Fifty-three in-patients with osteoarthritis of the hip (n = 34) or the knee (n = 19) were treated for 3 weeks with 400 mg vitamin E (d-alpha-tocopherolacetate, V, n = 26) or 50 mg Diclofenac (D, n = 27) three times daily. A standardized therapeutic exercise program was performed; local therapy was not permitted. There were no significant differences in the efficacy of the two drugs, although one patient of the V-group refused further treatment after 8 days because of inefficacy. V reduced or abolished the pain at rest in 77% (D in 85%), the pain on pressure in 67% (D in 50%), and the pain on movement in 62% (D in 63%). Both treatments appeared to be equally effective in reducing the circumference of the knee joints (p = 0.001) and the walking time (p less than 0.001) and in increasing the joint mobility (p less than 0.002). Patients (n = 11) with a plasma-alpha-tocopherol increase higher than two standard deviations of the mean value at onset (greater than 25.2 mg/l) seemed to have a more pronounced reduction of pain (eight out of 11 patients) compared with four out of 11 patients with a moderate increase of vitamin E. Side effects occurred in two out of 26 patients with V (7.7%), and in 25.9% during D-treatment. One patient with D therefore stopped the therapy after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)