British journal of rheumatology最新文献

Objective: To evaluate the effect of early 'aggressive' drug treatment on radiographic progression in patients with recent-onset rheumatoid arthritis (RA), compared to conventional stepwise increasing intensity of treatment.

Design: Prospective follow-up study with an experimental group and a historical control group both divided into a high-risk subgroup and a low-risk subgroup, based on prognostic factors. The effect of the 'aggressive' and the conventional treatment strategy was compared between both high-risk groups; the low-risk groups, both treated according to the conventional treatment strategy, were used to ensure internal consistency between the experimental and the historical groups.

Patients: A total of 228 consecutive patients with recent-onset RA (complaints < 1 yr at study entry).

Methods: The 'aggressive' drug treatment consisted of institution of relatively fast-acting disease-modifying anti-rheumatic drugs (DMARDs) (sulphasalazine, methotrexate) immediately after diagnosis, and rapid adjustment of dosage and/or drug in the case of insufficient response as measured by a change in C-reactive protein (CRP) level. Radiographic damage was assessed according to a modified version of Sharp's method and cumulative disease activity expressed as CRP-area under the curve (CRP-AUC). The occurrence of side-effects was also evaluated.

Results: After 2 yr of follow-up, comparison of the two high-risk subgroups showed the radiographic progression in the 'aggressively' treated subgroup to be significantly lower than that in the control group [Sharp score: median (range) 26 (0-100) vs 35 (1-188); P = 0.03]. Cumulative CRP values were also significantly lower than in the control high-risk subgroup [CRP-AUC: median (range) 1963 (212-8515) vs 3025 (46-15 632) mg.week/1; P = 0.002). This was achieved without an increase in the occurrence of side-effects. There was no difference between the two low-risk subgroups with regard to entry characteristics, CRP-AUC values or radiological progression, indicating comparability between the two groups.

Conclusion: Early 'aggressive' drug treatment, using sulphasalazine and/or methotrexate, aimed at reduction of the CRP level, significantly reduces the (rate of) radiographic progression in RA.

Autoantibodies against calpastatin have recently been described to be highly prevalent in sera of patients with rheumatoid arthritis (RA). When the sera of 45 patients with RA were analysed for autoantibodies against calpastatin by a newly developed enzyme-linked immunosorbent assay (ELISA), only four sera (8.9%) tested positive, which is not significantly different from the frequency observed in healthy controls. Since the ELISA is based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin bound to the solid phase, this negative result might be the consequence of the small antigen used. Therefore, a systematic analysis of the epitopes for autoantibodies in calpastatin was performed using sera from RA patients and healthy individuals. Recombinant fusion proteins containing fragments of calpastatin or the complete protein were produced and sera analysed by Western blots. In the N-terminal portion (amino acids 1-369), at least two major epitopes exist, against which 65% of normal sera as well as 76% of RA sera show reactivity in Western blot assays. These epitopes are not useful for clinical diagnostics. Only five out of 45 (11.1%) RA sera reacted against the C-terminal portion (amino acids 363-708) of calpastatin, while four out of 52 (7.7%) control sera showed reactivity. Three of the five RA sera and two out of four control sera had autoantibodies against the C-terminal 27 amino acids of calpastatin. These three patient sera had already been tested positive in the ELISA. The fourth patient positive in the ELISA was Western blot negative. The differences between the group of RA patients and controls are not statistically significant. When the clinical characteristics of the four patients with autoantibodies against the carboxyl end of calpastatin were analysed, it became apparent that all four had significantly elevated C-reactive protein (>50 mg/l). This observation might indicate that calpastatin autoantibodies are found in RA patients with more active disease. Thus, while the majority of RA patients do not have an increased prevalence of calpastatin autoantibodies, it cannot be ruled out definitively that a small subgroup may be characterized by autoantibodies to the C-terminus of calpastatin.

Objective: Geographic differences in the prevalence of hip osteoarthritis (OA) have been ascribed to differences in the frequency of acetabular dysplasia among different ethnic groups. However, there are few data on the shape of the acetabulum in various populations around the world. We examined this issue in samples of pelvic radiographs from Britain and Japan.

Methods: Measurements were made on the pelvic radiographs of 1303 men and 195 women, aged 60-75 yr, who attended for i.v. urography in two British centres. These were compared with 99 men and 99 women aged 60-79 yr who were included in a population-based study in a rural community in Japan, and who agreed to undergo standardized pelvic radiography. Acetabular dysplasia was assessed by morphometric measurement of the centre-edge (CE) angle and acetabular depth.

Results: The mean CE angle among men was 36 degrees (95% CI 35-37 degrees ) in Britain and 31 degrees (95% CI 29-32 degrees ) in Japan; that in women was 37 degrees (95%, CI 36-38 degrees ) in Britain and 31 degrees (95% CI 29 33 degrees ) in Japan. The mean values of acetabular depth were also significantly (P < 0.001) lower in Japan than in Britain. However, the prevalence of hip OA was lower in Japan (0% in men, 2% in women) than in Britain ( 11% in men, 4.8 / in women). In a random effects model, there were negative relationships between measures of acetabular dysplasia and minimum joint space among individuals.

Conclusions: We conclude that there are marked differences in pelvic morphometry between Britain and Japan. The acetabular dimensions of Japanese subjects are considerably shallower than those of their British counterparts of similar age and sex. Nevertheless, hip OA is more frequent in Britain than in Japan. Further studies are required on the risk factors for hip OA in Oriental populations, in order that the aetiology of this disorder can be better understood.

Objective: Quadriceps sensorimotor dysfunction may be important in the pathogenesis of knee osteoarthritis (OA) and a determinant of disability. Exercise regimes can increase quadriceps strength, but whether this improves proprioception and reduces disability is uncertain. Moreover, research regimes involve protracted treatment which is clinically impracticable.

Methods: We compared quadriceps sensorimotor function and disability in 60 patients with knee OA, before and after an exercise regime, with a control group (n = 37) who did not exercise.

Results: Exercise improved quadriceps strength (mean change, 95% CI; 73 N, 26-19 N), voluntary activation (14%, 5-20%), knee joint position sense (0.6 degrees, 0.1-1.8 degrees), and reduced the Lequesne Index (3.5, 0.5-4) and aggregate time of four activities of daily living (8.4 s, 0.2-16.7 s). At 6 month follow-up, these improvements were maintained. The parameters of the control group were unchanged.

Conclusions: These results substantiate the association between quadriceps sensorimotor dysfunction and disability, emphasizing the importance of quadriceps exercise in the management of knee OA. The regimen is relatively brief and clinically practicable, but could be adapted to make it more cost effective.