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Biomedical subjects

M F Shadforth

Publications and source records attributed to M F Shadforth.

At least 19 recordsLinked to original sources
PubMed1991

Should disease-modifying agents be used in mild rheumatoid arthritis?

A 12-month double-blind controlled study comparing hydroxychloroquine 400 mg daily with placebo in 104 patients with mild RA was conducted to see whether patients with mild rheumatoid arthritis (RA) benefit from treatment with disease-modifying agents. Mild RA was defined as synovitis limited to the hands and feet, an ESR less than 30 mm/h and C-reactive protein less than 20 mg/l, a situation where accepted clinical practice is to use a non-steroidal anti-inflammatory agent alone. By 6 months, the improvement of clinical and laboratory parameters in the hydroxychloroquine treated patients was significant compared with pretreatment levels and significantly greater than the control group. This improvement was maintained at 12 months. In addition, fewer patients withdrew through lack of efficacy, eight on hydroxychloroquine versus 18 on placebo. The implications of treating this well defined group of patients is discussed.

Arthritis, Rheumatoid↗
PubMed1991

The association and predictive value of the complex immunoglobulin A-alpha 1-antitrypsin in the development of erosions in early rheumatoid arthritis.

Immunoglobulin A-alpha 1 antitrypsin complex (IgA-AT), its constituent components and nine other clinical or laboratory variables were measured in thirty-three patients with early, non-erosive rheumatoid arthritis (RA) in order to assess their value in predicting the subsequent development of erosions. After 12 months, eighteen patients had developed erosions. Comparison of variables measured at outset between the group of patients subsequently developing erosions and those not, showed only the complex IgA-AT level to be significantly different, the mean being higher in the erosive group. In the subgroup of patients with high IgA-AT levels (greater than 3.0 arbitary units) all developed erosions. The possible therapeutic implications of these findings are discussed.

Arthritis, Rheumatoid↗
PubMed1990

Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis.

An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.

Adult↗
PubMed1989

Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo-controlled study.

We studied combination therapy with two slow-acting antirheumatic drugs given concurrently in active rheumatoid arthritis (RA). A 12-month prospective randomized controlled trial compared gold and hydroxychloroquine in 52 patients to gold and placebo in 49. The patients continued to receive non-steroidal anti-inflammatory drugs and analgesics. They were selected from three rheumatology centres in the West Midlands. Combination therapy led to a greater number of withdrawals due to adverse reactions (18 cases compared to 10 receiving gold/placebo). Patients completing 12 months' therapy (27 taking gold/hydroxychloroquine and 32 on gold/placebo) were compared using five clinical, seven laboratory, and one radiological measure. All 13 variables favoured gold/hydroxychloroquine with an overall advantage of 20-25% for the combination. This only reached statistical significance (at the 1% level) for C-reactive protein. An overall disease activity index was better at 12 months (at the 5% level) and showed a more rapid response with gold/hydroxychloroquine. This is the first randomized prospective placebo-controlled trial to show a significant advantage from a combination of two slow-acting drugs. There are many different ways of giving such combinations and we consider these should be explored to maximize the effectiveness of treatment for RA.

Adult↗
PubMed1988

Measurement of natural killer cell cytotoxicity by area under a cytotoxic curve. A method suitable for rheumatoid arthritis.

Calculation of the area under a curve derived from a 51Cr cellular release assay gives a reproducible expression of cellular cytotoxicity and correlates well with results at fixed lymphocyte-to-target cell ratios and with lytic units at 20% and 30% cytotoxicity. This method is suitable for quantifying the low cytotoxicity seen in rheumatoid arthritis. The area under the cellular cytotoxic curve may be calculated using a simple mathematical formula or by computer analysis.

Arthritis, Rheumatoid↗
PubMed1987

The relationship between the complex of immunoglobulin A and alpha-1-antitrypsin, its constituent components and the acute-phase response as measured by C-reactive protein in rheumatoid arthritis treated with gold or D-penicillamine.

Serum levels of immunoglobulin A (IgA), alpha 1-antitrypsin (AT), their complex (IgA-alpha 1AT) and C-reactive protein (CRP) were measured prior to treatment and at 6 months, in 45 rheumatoid arthritis (RA) patients. Twenty-five patients were treated with D-penicillamine (DPA) and 20 patients with gold (sodium aurothiomalate). The level of circulating complex was reduced by both treatments (p less than 0.001). There was a significant correlation between the circulating levels of IgA-alpha 1AT complex and serum IgA (p less than 0.05). No relationship was observed between the level of circulating complex and CRP. These findings suggest that formation of IgA-alpha 1AT complex in RA is dependent on the level of IgA. The complex is reduced by gold and DPA but it does not reflect an acute phase response as measured by CRP.

Acute-Phase Proteins↗
PubMed1986

Rheumatoid arthritis: treatment which controls the C-reactive protein and erythrocyte sedimentation rate reduces radiological progression.

One hundred and fifty consecutive patients with active, rheumatoid arthritis were assessed and treated with gold, D-penicillamine, chloroquine or dapsone. Four groups were selected from these patients. Group I consisted of 60 patients who did not complete 12 months' therapy. Group II consisted of patients in whom ESR and C-reactive protein (CRP) fell to less than 30 mm/h and less than 20 mg/l, respectively, and remained at these levels between 6 and 12 months. In group IV the ESR and CRP fell but remained greater than 30 and greater than 20, respectively, during the same period. Group III patients had variable ESRs and CRPs between 6 and 12 months. In groups II, III and IV there was a significant deterioration (p less than 0.01) in the hand and foot radiographs from 0 to 6 months. Between 6 and 12 months the radiographs in groups III and IV continued to show significant radiological progression (p less than 0.01), but those of group II did not alter. These results suggest radiological deterioration continues during the first 6 months regardless of clinical response but thereafter, further deterioration is less likely to occur when the ESR and CRP are consistently controlled.

Arthritis, Rheumatoid↗
PubMed1986

Prediction of progressive joint damage in patients with rheumatoid arthritis receiving gold or D-penicillamine therapy.

Seventy two patients with classical or definite rheumatoid arthritis (RA) were randomly allocated to receive gold or D-penicillamine therapy (DPA) in a prospective study designed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy. Forty five patients completed 12 months' treatment. There were no significant demographic or clinical differences between them and the 27 drop outs. Twenty of the 45 patients showed no radiological progression between six and 12 months. These patients had less severe initial radiological damage, lower levels of serum aspartate transaminase (serum AST) and lactic dehydrogenase (LDH), but higher levels of serum cholesterol. Twenty five patients did show progression during the six to 12 month period. This group included all the men with nodules. Of the 43 pretreatment clinical and laboratory variables examined, however, the majority failed to predict whether or not progression would subsequently occur. This included the acute phase response and seropositivity.

Arthritis, Rheumatoid↗
PubMed1986

Calculating radiological progression in rheumatoid arthritis.

We examined two methods of calculating radiological progression in rheumatoid arthritis using hand and wrist radiographs scored by Larsen's method. Progression over 12 months was calculated in two ways: absolute change in score; relative change in score. The two methods of scoring progression were investigated in two studies. In the first 173 patients with rheumatoid arthritis treated with a variety of non-steroidal and slow-acting anti-rheumatic drugs were evaluated. There were different results using absolute and relative changes in score. Relative changes gave more meaningful results. The second study looked at 80 rheumatoid patients treated with slow-acting drugs for 6 months; patients with a persistently high ESR had significantly more progression assessed by relative change but not by absolute change. Evaluating the progression of joint damage by methods employing a scoring system must be interpreted with caution. Relative change may provide a more valuable measure than absolute change.

Anti-Inflammatory Agents↗
PubMed1984

Report on chloroquine and dapsone in the treatment of rheumatoid arthritis: a 6-month comparative study.

A controlled study compared 6 months' treatment of 60 patients with rheumatoid arthritis (RA). Half were randomly allocated to treatment with chloroquine 250 mg daily, the other half dapsone 100 mg daily (50 mg/day for the first 7 days) following a one-month run-in assessment period. All patients had active or progressing disease. Both treatment groups showed significant improvement in morning stiffness, number of painful joints, pain scores, Ritchie index, and proximal interphalangeal joint size, and the chloroquine group alone in grip strength. Laboratory tests showed significant decreases in erythrocyte sedimentation rate, C-reactive protein, and total serum protein levels, with significant increase in serum albumin in the dapsone group, where there was a significant mean drop in haemoglobin (less than 1 g/dl) and a rise in serum bilirubin, associated with its haemolytic effect. X-ray erosion scores were not significantly affected. The clinical and laboratory responses became evident by the time of the 2-month assessment. Criteria for clinical and laboratory improvement were defined, according to which there were 21/26 improvers in the chloroquine group and 12/29 in the dapsone group. It is concluded that although both are effective preparations, chloroquine showed a significantly higher improvement rate and was certainly better tolerated. It is the preferred treatment for patients with active or progressive disease not controlled by nonsteroidal anti-inflammatory drugs, with dapsone as an alternative for patients who fail to respond to or cannot tolerate chloroquine.

Arthritis, Rheumatoid↗
PubMed1983

Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis.

Plasma and synovial fluid concentrations of diclofenac sodium and its principal hydroxylated metabolites have been measured in sixteen rheumatoid patients on chronic therapy to investigate possible reasons for the drug's extended duration of action despite its apparent short elimination half-life in plasma. Diclofenac was detected in synovial fluid 2 h after dosing but at a lower level than in plasma. Thereafter synovial fluid concentrations remained relatively constant through to 11 h post-dosing whereas plasma levels in the same period declined rapidly from an initially high peak to near the sensitivity limit of the assay. Hydroxylated metabolites (free + conjugated) were rapidly formed with measurable concentrations of the 4' and 5 mono and dihydroxy derivatives being detected in plasma 2 h after dosing; levels of the 3' hydroxy metabolite were negligible at this time. Initially plasma levels of all metabolites were higher than those in synovial fluid but after 4 h synovial fluid levels were equal to or slightly higher than those in plasma. The significance of these findings is discussed in relation to the drug's overall clinical effect.

Arthritis, Rheumatoid↗
PubMed1983

Acetylator phenotype and the effect of dapsone in rheumatoid arthritis.

Acetylator phenotype was determined in 54 patients with rheumatoid arthritis (RA) taking dapsone in the course of 2 comparative clinical studies. No significant differences were demonstrated in the assessments, either of efficacy or adverse effects. There appears to be no clinical advantage in assessing acetylator phenotype in patients with RA being treated with dapsone.

Acetylation↗
PubMed1978

Examination of complement C3 metabolism in rheumatoid arthritis using 2-dimensional immunoelectrophoresis.

A previous report that C3 activation products are demonstrable in the plasma of subjects with rheumatoid arthritis was reinvestigated using 2-dimensional immunoelectrophoresis. Initially it seemed that results were in agreement, but the occurrence of similar patterns in normal sera and poor reproducibility of results suggested the findings were artefacts. When calcium and magnesium ions were removed with EDTA, C3 activation products were no longer demonstrable in plasma from normal subjects or from patients with rheumatoid arthritis. The results obtained without EDTA in the buffer showed a greater degree of complement activation in patients with rheumatoid arthritis, suggesting that in this condition the serum may have a greater potential ability to bring about complement activation.

Adult↗