Antineutrophil cytoplasmic antibody titres in patients with recent infection.
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Biomedical subjects
Publications and source records attributed to H A Capell.
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There are few 'second-line' drugs available for the treatment of PSA and their use is often limited by toxicity. Thirty-nine patients with active PSA recruited from two rheumatology units were randomly allocated to either enteric-coated sulphasalazine (SASP) or placebo and followed for 24 wk. Six patients in the SASP group and 11 on placebo discontinued therapy before 24 wk. Evaluation of effect of treatment revealed significant improvements in articular index in both groups at 12 wk. By 24 wk the articular index in placebo group was still showing benefit. In addition to articular index the SASP group improved significantly in terms of visual analogue scale, duration of morning stiffness and ESR. SASP is effective in PSA but the partial clinical response to placebo indicates the importance of placebo-controlled studies in this variable disease.
The natural history of RA over a period of 6 months is not known, but this is of central importance to the design and interpretation of drug trials of possible DMARDs. We analysed the disease activity of 142 rheumatoid patients who were randomized to receive placebo in five double blind, placebo-controlled trials of possible disease-modifying drugs conducted in a single unit. There was no significant change in ESR, duration of morning stiffness or platelet count over a period of 6 months; the mean change in ESR at 3 months was an increase of 2 mm/h (99% C.I. -3, +7), and only 5% of patients more than halved their ESR over 6 months. There was a small significant fall in articular index over 6 months of placebo treatment. There is no measurable placebo effect on ESR, morning stiffness or platelet count when these are used as measures of disease activity in trials of drug therapy in RA. ESR is an informative, stable measure of disease activity; the duration of morning stiffness may be more useful than the articular index. The use of these results as the basis of a historical cohort to help design future placebo-controlled trials, and to interpret uncontrolled trials of putative anti-rheumatic drugs is discussed.
Serum soluble interleukin 2 receptor (sIL-2R) concentrations reflect lymphocyte activation in vivo. An investigation was carried out to determine if sIL-2R concentrations correlate with existing disease activity parameters in patients with rheumatoid arthritis (RA) and whether these concentrations are modulated by treatment with second line drugs. Seventy nine patients with rheumatoid arthritis with active disease were prospectively treated with sodium aurothiomalate, auranofin, or sulphasalazine. Sequential concentrations of sIL-2R were measured by enzyme linked immunosorbent assay (ELISA). No correlations were observed between sIL-2R concentrations and clinical parameters and there were only moderate associations with concentrations of C reactive protein and the erythrocyte sedimentation rate. Concentrations of sIL-2R did not significantly change with treatment. It is concluded that sIL-2R probably measures an aspect of rheumatoid synovitis distinct from acute phase reactants and is not influenced by treatment with second line drugs.
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In rheumatoid synovium interleukin 6 (IL-6) is the most abundantly expressed cytokine. Increased serum levels have been previously reported in patients with rheumatoid arthritis (RA). In this study serum IL-6 levels were measured in a well defined cohort using a bioassay (B9 cells) and levels were correlated with conventional clinical and laboratory indices of disease activity. Levels were significantly higher in serum from patients with RA (median 55 IU/ml; interquartile range 28-139) compared with serum from disease (median 7 IU/ml; 1-23) and normal controls (median 10 IU/ml; 7-12). No difference was observed between men and women. Levels did not correlate with disease duration. Significant associations were observed between IL-6 and C reactive protein and between the Ritchie articular index and duration of morning stiffness. No other correlations were observed. The value of these findings in the monitoring of RA and as an indicator of response to second line treatment needs to be established.
OBJECTIVES: The objectives were to assess (a) the comparative merits of commonly used disease modifying drugs in the treatment of rheumatoid arthritis (RA) and (b) the influence of age, gender, and disease duration on the outcome of treatment. METHODS: Collected analysis (meta-analysis) was performed on results obtained during the first year of treatment in 1140 patients with RA treated with gold, penicillamine, sulphasalazine, or auranofin from a single centre. RESULTS: Gold, penicillamine, and sulphasalazine performed similarly, with about 60% of patients continuing to receive each of these drugs for at least one year. Neither gender nor age had an influence on the response to treatment, but patients with a longer disease duration showed a greater tendency to stop treatment. The median percentage improvement was 33% in visual analogue pain score and 50% in erythrocyte sedimentation rate. CONCLUSIONS: Routine use of these drugs should at least equal these results. Any new drug should either be substantially less toxic or at least as efficacious.
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OBJECTIVE: To determine the clinical utility and the effect of sodium aurothiomalate (GSTM) on serum interleukin 6 (IL-6) levels in patients with rheumatoid arthritis (RA). METHODS: Open prospective study of 50 patients with RA treated with GSTM. Serum IL-6 measured by bioassay. RESULTS: IL-6 showed correlations with Ritchie articular index, duration of morning stiffness and C-reactive protein. GSTM significantly reduced IL-6 levels. CONCLUSIONS: IL-6 is a potentially useful additional indicator of disease activity in RA and is modulated by GSTM.
OBJECTIVE: To determine if there is any advantage in adding hydroxychloroquine to intramuscular gold therapy in patients with rheumatoid arthritis (RA) with a suboptimal response to gold after 6 months of treatment. METHODS: Prospective double blind placebo controlled study at the Centre for Rheumatic Diseases, Glasgow Royal Infirmary and Gartnavel General Hospital, Glasgow. Patients--440 patients with RA began intramuscular gold therapy. One hundred forty-two patients with a suboptimal response at 6 months were randomized to receive additional treatment with hydroxychloroquine (400 mg/day) or placebo, and followed for a further 6 months. Outcome measures were erythrocyte sedimentation rate, C-reactive protein, Ritchie articular index, grip strength, visual analog pain score, duration of morning stiffness, health assessment questionnaire, and rate of side effects. RESULTS: There was no difference in outcome in terms of efficacy or toxicity. CONCLUSION: There is no justification for using a combination of intramuscular gold and hydroxychloroquine in patients with RA with a partial response to gold.
Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation.
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Two hundred patients with rheumatoid arthritis were studied in a prospective open trial comparing treatment with sulphasalazine and auranofin in patients with active disease over 12 months. The two drugs improved many parameters of disease activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte sedimentation rate, and articular index, with a greater decrease in erythrocyte sedimentation rate (Students t test) and C reactive protein between 0 and 12 weeks. There were no significant differences between sulphasalazine and auranofin treatment after 24 and 48 weeks. Life table analysis showed no significant differences in the rate of side effects which caused treatment to be stopped. Sulphasalazine works more rapidly, may be a more effective disease modifying antirheumatic drug, and is as well tolerated as auranofin.
Anecdotal reports suggest that metronidazole may have disease modifying activity in the treatment of rheumatoid arthritis. To assess possible beneficial effects a double blind, comparative trial of metronidazole and placebo was performed. Fifty patients with active rheumatoid arthritis were randomly allocated to receive active drug (n = 24) or placebo (n = 26) and reviewed at weeks 0, 1, 4, 8, 12, 16, and 24. Detailed assessment of drug safety, biochemical and haematological parameters, and efficacy was made at these dates. Dose regimen was 400 mg twice daily from weeks 0 to eight, increasing to 400 mg three times a day from weeks nine to 24 provided that no adverse effects were recorded. Most patients were unable to tolerate metronidazole because of side effects or lack of efficacy, with only five (21%) continuing to take the drug at 24 weeks. For those patients attaining 12 weeks of treatment an overall improvement in articular index and morning stiffness was found. No improvement in laboratory indices of disease activity was seen, however. In this study metronidazole did not have disease modifying properties and was unacceptably toxic.
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15 patients with rheumatoid arthritis who were receiving non-steroidal anti-inflammatory drugs (NSAIDs) and who had chronic occult gastrointestinal bleeding underwent extended small bowel examination with a Sonde enteroscope. 7 patients (47%) were found to have jejunal or ileal ulceration. Small bowel enteroscopy may be a valuable technique for the investigation of undiagnosed gastrointestinal bleeding.
Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6 g/day) and 21 received placebo (olive oil 6 g/day). No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits.
OBJECTIVE: To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud's phenomenon secondary to connective tissue disorders. DESIGN: Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks. SETTING: Rheumatology units, five teaching hospitals. PATIENTS: 55 Patients with Raynaud's phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren's syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis. INTERVENTIONS: All other treatment for Raynaud's phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud's phenomenon. Assessment of ulcer and ischaemic lesion healing. RESULTS: Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud's attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects. CONCLUSIONS: Both dosage regimens reduce severity of Raynaud's phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.