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Biomedical subjects

H A Capell

Publications and source records attributed to H A Capell.

At least 55 records · Page 3Linked to original sources
PubMed1996

Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis.

OBJECTIVE: To examine the proposal that pretreatment low dose desensitisation may reduce the incidence of toxicity of sulphasalazine in the treatment of rheumatoid arthritis (RA). METHODS: A double blind, placebo controlled trial was performed with 422 patients satisfying the American College of Rheumatology criteria for RA who required sulphasalazine treatment because of increased disease activity. Patients received either sulphasalazine desensitisation, or placebo, for three weeks before commencement of sulphasalazine treatment. The frequency and nature of adverse effects and changes in clinical and laboratory parameters of disease activity were measured after three and six months. RESULTS: Improvement in the efficacy of sulphalasazine (measured by clinical and laboratory parameters) was significant and similar in magnitude in both groups. There was no significant difference between actively and placebo desensitised patients as regards the incidence or profile of adverse effects (toxicity). CONCLUSION: Pretreatment low dose desensitisation is unhelpful in reducing the toxicity associated with sulphasalazine treatment of RA.

Anorexia↗
PubMed1996

The use of antimalarials in combination with other disease modifying agents in RA--the British experience.

Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination therapy due to their efficacy, mechanisms of action and toxicity profile. In this review, the evidence for the use of antimalarials in combination in RA is examined. No advantage has been shown in combining antimalarials with gold, penicillamine or sulphasalazine compared with monotherapeutic regimens. There is some evidence to suggest a beneficial combination of antimalarials with methotrexate, but this is as yet inconclusive. Open non-randomised uncontrolled studies have shown that antimalarials combined with cytotoxic agents are effective but highly toxic. The authors conclude that there is little good evidence to support the introduction of combination second-line drug therapy for RA into widespread therapeutic use.

Antimalarials↗
PubMed1996

Sulfasalazine has a better efficacy/toxicity profile than auranofin--evidence from a 5 year prospective, randomized trial.

OBJECTIVE: To compare results of medium to longterm sulfasalazine and auranofin treatment in active rheumatoid arthritis (RA). METHODS: 200 patients with active RA were enrolled in a prospective, randomized trial comparing sulfasalazine (target dosage, 40 mg/kg/day) with auranofin (6-9 mg/day). Patients were assessed annually for 5 years, using clinical and laboratory measures of disease activity. Risk of discontinuing treatment was compared using life table analysis. RESULTS: 31% of patients continued sulfasalazine for at least 5 years, compared to only 15% continuing auranofin (p < 0.05). Patients previously given intramuscular (i.m.) gold did particularly badly during auranofin treatment (only 1/26 continued therapy for 5 years), but after excluding all patients previously treated with i.m. gold from both groups more patients continued sulfasalazine for > 5 years (p < 0.05). Patients continuing therapy at 5 years had significantly milder disease at enrollment than those who did not. The patients continuing auranofin treatment at 5 years were no better than at the outset of the trial, and may represent a subgroup of patients with a good prognosis. Patients continuing sulfasalazine, however, showed sustained response over the 5 year period. CONCLUSION: Sulfasalazine therapy was more likely to be continued for 5 years, suggesting better tolerability and/or efficacy than auranofin, and produced evidence of continuing benefit. Patients previously withdrawn from i.m. gold therapy because of inefficacy or minor toxicity should not be given auranofin therapy.

Antirheumatic Agents↗
PubMed1995

Effect of cyclosporin A on interleukin-6 and soluble interleukin-2 receptor in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effect of cyclosporin A (CyA) therapy on circulating concentrations of interleukin-6 (IL-6) and soluble interleukin-2 receptor (sIL-2R) in patients with rheumatoid arthritis (RA). METHODS: Twenty four RA patients with active disease were studied. Plasma was collected before and after 16 weeks of CyA treatment. IL-6 was measured by B9 bioassay and sIL-2R by enzyme linked immunosorbent assay (ELISA). RESULTS: The initial median IL-6 concentration of 165 IU/ml decreased significantly to 71 IU/ml after 16 weeks (p < 0.05). Similarly, the initial median plasma sIL-2R value of 665 U/ml decreased significantly to 570 U/ml (p < 0.05). This decrease was accompanied by an improvement in clinical parameters of disease activity. Some association between sIL-2R, IL-6, haemoglobin, and platelets was also observed. CONCLUSIONS: This study has demonstrated that, in vivo, CyA therapy in RA can significantly reduce circulating concentrations of IL-6 and sIL-2R. Modulation of both T and non-T cell derived cytokines may be one mechanism by which CyA improves rheumatoid disease. Whether this is a direct effect of CyA on the cells within the rheumatoid joint producing these cytokines or an indirect effect mediated by other cytokines which can influence IL-6 and Il-2R values remains to be determined.

Adult↗
PubMed1995

Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.

OBJECTIVE: To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome. METHODS: The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later. RESULTS: Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24). CONCLUSION: Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance.

Administration, Oral↗
PubMed1995

Interleukin 6 (IL-6) and soluble IL-2 receptor levels in patients with rheumatoid arthritis treated with low dose oral methotrexate.

OBJECTIVE: To investigate the effect of oral methotrexate (MTX) on circulating levels of interleukin 6 (IL-6) and soluble IL-2 receptor (sIL-2R) in patients with rheumatoid arthritis (RA). METHODS: We measured serum concentrations of IL-6 (n = 20) and sIL-2R (n = 16) before MTX therapy and again after 12 weeks. RESULTS: MTX significantly reduced IL-6 and sIL-2R after 12 weeks of therapy, and although the levels remained low at 24 weeks of therapy, the reduction was not significant. Reduction in cytokine levels was paralleled by an improvement in clinical indices. Placebo treatment did not significantly alter IL-6 or sIL-2R. CONCLUSION: MTX appears capable of cytokine modulation, although the mechanism is not clear.

Administration, Oral↗
PubMed1995

Clinical efficacy of sulphasalazine--a review.

This review of the use of sulphasalazine (SASP) in the therapy of rheumatoid arthritis refers to the placebo-controlled trials of SASP and the randomized comparative studies with other second-line drugs that have been published over the past decade. The questions relating to appropriate selection of patients for this treatment and the possible relevance of drug interactions are addressed. The favourable effect of SASP on functional, radiological and extra-articular outcome measures is highlighted, as is the reproducibility of published studies. Finally, the results from combination studies and meta-analyses are outlined.

Antirheumatic Agents↗
PubMed1994

Production of interleukin-6 by monocytes isolated from rheumatoid arthritis patients receiving second-line drug therapy.

IL-6 production by peripheral blood monocytes isolated from RA patients receiving the second-line drugs auranofin (AUR), sulphasalazine (SASP) or gold sodium aurothiomalate (GST) was investigated. In patients receiving AUR a significant reduction in both basal and lipopolysaccharide (LPS) stimulated IL-6 production by isolated cells was observed. Similarly, SASP significantly reduced basal IL-6 production. In contrast, monocytes isolated from individuals receiving GST had no significant change either in basal or LPS stimulated IL-6 production. We suggest an effect by AUR and SASP either on pre-monocytic cells in the bone marrow or on monocytes in the periphery may subsequently result in a reduction in IL-6 production by these cells once they have infiltrated the RA joint. This may be one way by which these therapies contribute to the beneficial effects seen in patients receiving these treatments.

Arthritis, Rheumatoid↗
PubMed1994

Short report: the effect of misoprostol on the anaemia of NSAID enteropathy.

BACKGROUND: Small bowel ulceration is an increasingly recognised complication of therapy with non-steroidal anti-inflammatory drugs (NSAID). The ulceration is a potent site of blood loss contributing to unexplained iron deficiency anaemia in patients with arthritis. No drug is currently available to treat NSAID small bowel ulcers. METHODS: We have retrospectively examined the effect of therapy with the prostaglandin E1 analogue misoprostol on the anaemia of patients with enteroscopically proven NSAID small bowel enteropathy. RESULTS: All of the patients had proven iron deficiency anaemia. Eleven patients received misoprostol and ten received no treatment. Haemoglobin in the misoprostol-treated group rose significantly from median (range) 9.1 (6.2-10.6) g/dL (95% confidence intervals 8.76, 10.13) to 10.6 (6.5-16.8) g/dL (95% confidence intervals 10.06, 11.82); P = 0.004). Those patients who did not receive misoprostol had no significant change in their haemoglobin: 9.1 (7.5-10.6) g/dL to 8.1 (5.6-14.7) g/dL (P = N.S.). CONCLUSION: Misoprostol therapy was associated with an improvement in the anaemia in patients with proven NSAID enteropathy.

Adult↗
PubMed1994

Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study.

AIMS: To study the effects of ovarian hormone replacement therapy (HRT) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis (RA). METHOD: A placebo controlled double-blind study was carried out on 62 patients with RA, 22 on placebo and 40 on HRT (transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinically indicated). Bone mineral density of spine, hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0, 12, 24 and 48 weeks. RESULTS: Thirteen of 22 (59%) of placebo and 31 of 40 (78%) of the HRT group completed 48 weeks in the study. At entry, bone mineral density (BMD) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups, whereas at the distal radius, BMD was significantly reduced to approximately 50% of control values (both p < 0.001 from controls). In the HRT group, spine BMD increased significantly by a median of +0.94% at 48 weeks (p = 0.024), but did not change significantly in the placebo group. BMD at the femoral neck and distal radius did not change in either group. In the HRT group, there was significant improvement in well being as assessed by the Nottingham Health Care Profile (p < 0.01) and in the articular index (p < 0.05). There were no significant changes in ESR or CRP in either group. CONCLUSION: Transdermal HRT was well tolerated, increased well being, reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA. Although no laboratory evidence was found of a disease modifying effect, the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA.

Activities of Daily Living↗
PubMed1994

Outcome of second line therapy in rheumatoid arthritis.

OBJECTIVES: To study the functional outcome in patients with rheumatoid arthritis (RA) who tolerate second line drug therapy for five years. METHODS: We enrolled into prospective controlled trials, 190 patients with rheumatoid arthritis who tolerated 'disease modifying' antirheumatic drug therapy for five years. Demographic data were recorded. Disease activity was measured every six months for two years and annually thereafter, using clinical and laboratory variables. Patient function was measured using the modified Health Assessment Questionnaire. The change in each variable was analysed using paired Wilcoxon tests. RESULTS: Patient function improved significantly compared with baseline. The improvement was maximal after one to two years, and thereafter function started to decline slowly. After five years of treatment the patients' function was still significantly better than before treatment had started. There were highly significant improvements in all variables measured to assess disease activity, which remained well controlled throughout the five year period. CONCLUSION: Good control of disease activity and improved function can be achieved long term in approximately 30% of RA patients treated with injectable gold, sulphasalazine or penicillamine.

Adult↗
PubMed1994

The effect of azathioprine on serum levels of interleukin 6 and soluble interleukin 2 receptor.

Cytokine pathways are central to the perpetuation of synovial inflammation in rheumatoid arthritis (RA). Azathioprine (AZA) has disease modifying activity in RA. This study addressed the effect of AZA on serum IL-6 and soluble IL-2 receptor (sIL-2R) levels in RA. Over a 24 week period of therapy significant clinical improvement was observed. However, serum levels of both IL-6 and soluble IL-2R levels did not significantly change after AZA therapy. AZA therapy did not significantly alter the peripheral blood monocytes ability to produce IL-6 in vitro, either in the presence or absence of LPS. The mechanism by which AZA achieves clinical improvement in RA patients does not appear to be through IL-6 modulation or modification of synovial lymphocyte activation as assessed by serum sIL-2R levels.

Adult↗
PubMed1993

The spectrum of disease associated with a positive ANCA.

This is a retrospective analysis of all patients with a raised titre of ANCA in a single centre over a two-year period. Sixty-five patients were identified and clinical data is presented for 58 of these-34 male and 24 female. The median age is 56 years (13-83). Fourteen patients had Wegener's granulomatosis, 14 microscopic polyarteritis nodosa and 30 had other diagnoses. The patients with unexpectedly positive results are discussed in detail. This study confirms the sensitivity of ANCA in Wegener's granulomatosis and microscopic polyarteritis nodosa but suggests that the test is not as specific as initially claimed.

Adult↗
PubMed1993

Toleration, side-effects and efficacy of sulphasalazine in rheumatoid arthritis patients of different ages.

Sulphasalazine is an effective second-line agent in the management of rheumatoid arthritis. The risk:benefit ratio in the elderly is less well established. We studied the risk:benefit ratio in relation to age, retrospectively combining five prospective studies of enteric coated sulphasalazine therapy in 352 patients with rheumatoid arthritis. Clinical and laboratory assessments of efficacy and toxicity were made by an independent assessor at 0, 12, 24 and 48 weeks. The only significant differences between young, middle aged and elderly patients at the initial assessment were in pain perception, ESR and C-reactive protein. Sulphasalazine was equally effective in all age groups. The toxicity profile was similar in all age groups. We conclude that sulphasalazine is equally effective in rheumatoid arthritis in the elderly as in the young. There was no significant change in the frequency or nature of side-effects with increasing age.

Adult↗