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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

298 records · Page 17Linked to original sources
PubMedDate not supplied

Treating rheumatoid arthritis early with disease modifying drugs reduces joint damage: a randomised double blind trial of sulphasalazine vs diclofenac sodium.

BACKGROUND: Current disease management in rheumatoid arthritis (RA) has moved towards "inverting the therapeutic pyramid" by introducing disease-modifying anti-rheumatic drugs (DMARDs) early. Despite the logic of early DMARD therapy, there is a dearth of supportive evidence for this approach. We report a randomised controlled trial comparing sulphasalazine monotherapy with diclofenac monotherapy in early RA. The primary aim was to provide unequivocal evidence that early DMARDs prevent erosive damage. The secondary aim was to evaluate if sulphasalazine used alone has comparable symptomatic benefits to NSAIDs. METHODS: 117 patients with RA for under 12 months of diagnosis (mean 2 months) were randomised (62 sulphasalazine; 55 diclofenac). Sulphasalazine patients comprised 76% women, and 58% were rheumatoidfactor positive. Diclofenac patients comprised 74% women, and 54% were seropositive. 36% completed 12 months of therapy (16 sulphasalazine; 26 diclofenac); sulphasalazine was given for a mean period of 21 weeks and diclofenac for a mean period of 33 weeks. Results were analysed on an intention to treat basis. RESULTS: After 12 months the mean number of new erosions in patients randomised to receive sulphasalazine was 2.0 (95%CI 0.9, 3.1) and in patients randomised to receive diclofenac was 7.5 (95%CI 4.1, 10.9; p = 0.002 by Student's unpaired t-test). An analysis of valid compliant completers showed the mean number of new erosions in patients who received 12 months therapy with sulphasalazine was 2.3 (95%CI 0.6, 4.0) and in patients who received 12 months diclofenac was 10.5 (95%CI 5.0, 15.9; p = 0.018 by Student's unpaired t-test). The Ritchie articular index, swollen joint counts and pain scores decreased with both sulphasalazine and diclofenac, with mean falls in both groups of 15-20% at 2 weeks and 30-40% at 4 and 8 weeks. There were no differences between treatments. Disease activity scores showed similar highly significant mean decreases within both treatment groups (P < 0.001 in all cases) of 0.5 at 2 weeks and 1.0 at 4 weeks; at 12 and 26 weeks they were significantly lower with sulphasalazine (p = 0.036 and 0.045). 75% of the patients given sulphasalazine and 65% of those given diclofenac had one or more adverse events with no major differences between treatments. CONCLUSIONS: These results show that an accelerated dosing schedule of sulphasalazine has identical effects to diclofenac in reducing symptoms, indicating it is a rapidly effective DMARD. They also provide unequivocal evidence, analysed on an intention to treat basis, that early treatment with sulphasalazine significantly reduces the extent of radiological progression in active RA.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Rheumatology and the gut.

Some conditions may present with gastrointestinal and rheumatological manifestations. Salmonella osteomyelitis results from direct infection of bone following gut infection and bacteraemia, but in other conditions the pathogenesis is less clear. There may be a microbial cause for rheumatoid arthritis; however, this theory remains unproven.

Diagnosis, Differential↗
PubMedDate not supplied

Disease activity in rheumatoid arthritis: preliminary report of the Consensus Study Group of the European Workshop for Rheumatology Research.

The most suitable measures to assess the disease activity of rheumatoid arthritis patients treated with slow-acting anti-rheumatic drugs were considered in a prospective study. This was organised across Europe in 12 specialised centres and 282 patients were studied. The patients were all considered to be in need of therapy with a slow-acting anti-rheumatic drug and were studied at the initiation of therapy, and after 3 and 6 months of treatment. There were 215 patients who remained on treatment for 6 months. The most useful measures to assess disease activity were: the number of swollen joints, the number of tender joints, pain, the patients' assessment of response, and ESR. These should form a minimum data set when assessing the activity of rheumatoid arthritis. Some measures such as grip strength, hemoglobin, and the C-reactive protein level showed too much variation between centres and will require considerable standardisation before they can be used across Europe. There were problems in collecting functional data and further work is needed to develop a functional questionnaire available in all European languages with culturally suitable questions.

Adult↗
PubMedDate not supplied

Joint damage and disability in rheumatoid arthritis: an updated systematic review.

Joint damage and disability in rheumatoid arthritis (RA) both increase with disease duration but the nature of their relationship is uncertain. This review updates knowledge of the progression and inter-relationship of joint damage and disability in treated RA and provides a synopsis of the main predictive factors for damage and disability. In early RA 39-73% of patients develop one or more erosions in their hands and wrists by 5 years. In established RA the average annual increase in radiological damage scores is 1.9% maximal damage. After 20 years RA patients have on average 43% of maximum possible damage. These data suggests that joint damage progresses constantly over the first 20 years of RA. The average annual increase in HAQ scores is 0.033 per year (1% of possible maximum disability). In the first years of disease there is a "J-shaped" curve with an initial fall in HAQ scores followed by an increase over the next four years. In cross-sectional studies there is either no correlation or a weak correlation between damage and disability in early RA; this absence of correlation is explained by the "J-shaped" curve of disability with disease duration in early RA. As disease duration increases the correlation between damage and disability becomes more obvious; 9 studies show correlation coefficients between 0.31 and 0.75. The most predictive factors of damage and disability are rheumatoid factor status and disease activity. The validity of our conclusions are limited by the potential indirect link between small joint damage and disability, with large joint damage being a more important predictor, and the presence of ceiling effects on X-rays. In conclusion, joint damage accounts for a substantial proportion of the disability associated with the disease.

Adult↗
PubMedDate not supplied

The consequences of rheumatoid arthritis: quality of life measures in the individual patient.

Despite conventional treatment, RA still has many deleterious consequences. From the patients' perspective, these include persistent pain, functional disability, fatigue, and depression modified by health beliefs and underlying psychological problems. Disability is a consequence of pain, active synovitis and joint damage. It is usually assessed by self-reported questionnaire; the Health Assessment Questionnaire (HAQ) remains the dominant disability measure, although generic health measures such as Short Form-36 and Nottingham Health Profile provide similar information. Treatment with disease modifying drugs and biologic agents improves pain, fatigue and disability. We specifically evaluated the effects of both these drugs and also disease duration on disability assessed by HAQ scores, as there is most information on this topic and it is of fundamental importance to patients. In early RA HAQ gives a 'J-shaped' curve; the initial fall is due to the immediate benefits of treatment and the subsequent gradual rise due to the inability of therapy to fully suppress the disease or prevent progressive joint damage. In established RA HAQ scores increase by about 1% annually and over 25 years average HAQ scores increase by 1.0. Disease modifying drugs and biologics both significantly reduce HAQ scores and the reduction is maintained for 2-5 years. This reduction is seen in both early and established disease. Early steroid therapy has immediate symptomatic treatment, but does not have long-term benefits. Over 5 years the impact of aggressive therapy with disease modifying drugs declines and there is evidence that insufficient treatment is given to many patients with RA. The outcome of RA is greatly improved by current treatment with disease modifying drugs and biologic agents. However, more needs to be done and achieving better results is enhanced by routinely measuring the impact of the disease in routine practice.

Arthritis, Rheumatoid↗
PubMedDate not supplied

The significance of fibronectin in cryoprecipitation in rheumatoid arthritis and other diseases.

Fibronectin, a glycoprotein produced by mesenchymal cells, was present in 11 of 16 plasma cryoprecipitates and 12 of 14 synovial fluid (SF) cryoprecipitates. In some SF cryoprecipitates it was the major protein component. Fibronectin levels were related to the development of serum turbidity in the cold and fibronectin was involved in the development of cold turbidity induced by some charged polysaccharides in plasma, serum, and SF. It is suggested that fibronectin, which is synthesized by vascular endothelial cells and synovial lining cells, is involved in the development of some cryoprecipitates in patients with rheumatoid arthritis and other diseases.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Cartilage contribution to gender differences in joint disease progression. A study with rat articular cartilage.

OBJECTIVE: Rheumatoid arthritis is associated with a worse prognosis in females and is influenced by sex hormone changes. Similar observations in osteoarthritis support the hypothesis that gender differences in cartilage make a hitherto unrecognized contribution to gender differences in arthritis. The aim of the present study was to investigate potential gender differences in articular cartilage biochemistry, metabolism and response to inflammatory mediators. METHODS: Femoral head cartilages from age-matched male and female Wistar rats were analysed for the water, glycosaminoglycan, hydroxyproline and collagen crosslink contents. Proteoglycan loss and synthesis were assessed in vitro, and in the presence and absence of serum and interleukin-1. An in vivo model of inflammation-induced cartilage degradation was employed to investigate gender differences in cartilage susceptibility to erosion caused by granulomatous tissue. RESULTS: Articular cartilage from male Wistar rats presented higher levels of both proteoglycan and collagen and showed a lower spontaneous glycosaminoglycan loss and higher proteoglycan synthesis in vitro than cartilage from females. Proteoglycan synthesis from female, but not male, cartilage was significantly stimulated by foetal calf serum. Female cartilage was more sensitive to IL-1 inhibition of proteoglycan synthesis while the opposite was observed in IL-1-induced proteoglycan loss. Female cartilage was more susceptible to granuloma-induced degradation than male when implanted into female mice, but no differences were observed between male and female cartilage implanted in male mice. CONCLUSION: These results demonstrate important gender differences in cartilage biochemistry, metabolism and susceptibility to inflammatory mediators which may have important consequences for the joint destruction in arthritis and support a role for hormone therapy.

Animals↗
PubMedDate not supplied

Rheumatoid synovial cell proliferation, transformation and fibronectin secretion in culture.

OBJECTIVE: There is some experimental evidence that patients with rheumatoid arthritis (RA) have a defect in the control of cellular proliferation. To examine this further, synovial cells from patients with RA and osteoarthritis controls (OA) were studied for phenotypic characteristics of transformation and proliferation. METHODS: Synovial cells grown in vitro were studied to determine the extent of proliferation, anchorage-independent growth, growth under reduced serum conditions, fibronectin secretion, and the presence of cell proliferation antigens. RESULTS: RA synovial cell proliferation was less than that recorded for normal skin fibroblasts and was not increased compared to OA synovial cells. Studies of growth in soft agarose showed no colony formation by RA or OA synovial cells after 28 days, indicating that anchorage-independent growth does not occur. At low serum concentrations RA and OA synovial cells showed similar growth. Fibronectin was constant for each cell line studied, irrespective of the cell number or diagnosis. RA cells did not show an increased rate of fibronectin secretion. RA cells did not show an increased expression of proliferating cell antigens. CONCLUSION: These studies do not support the concept that defective proliferation of synovial cells is a major factor in the pathogenesis of RA.

Animals↗
PubMedDate not supplied

The radiological assessment of rheumatoid arthritis.

Antirheumatic therapy has changed from a rather conservative approach towards more aggressive early intervention. Objective measures of the course and outcome of rheumatoid arthritis are essential to understand the disease process and evaluate the therapeutic response. Radiological evaluation fulfils many of the criteria of objectivity: the films provide a permanent record and can be evaluated serially and repeatedly; the changes do not fluctuate with disease activity; and good technique and correct timing can keep the radiation load to a very acceptable level. Consequently, therapies can be evaluated on the basis of their efficacy on radiological progression. In clinical practice, a visual qualitative assessment is usually sufficient, but for therapeutic trials or studies of disease progression in certain patient groups, quantitative methods are needed. A number of different evaluation systems have been introduced, but none of these have gained universal acceptance. No ideal evaluation method (which should be rapid, easy to use and have a good level of reproducibility) has yet been found. Here we make provisional recommendations on the conduct of future therapeutic trials to maximise the likelihood that they will give conclusive results using radiographic outcome assessments.

Antirheumatic Agents↗