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Biomedical subjects

P D Fowler

Publications and source records attributed to P D Fowler.

At least 19 recordsLinked to original sources
PubMed1991

Intra-articular steroids: confounder of clinical trials.

The effect of intra-articular (i-a) steroid injection on ESR and C-reactive protein (CRP) in rheumatoid arthritis (RA) was investigated. One week following injection of 1 or 2 knees there was a significant fall in ESR (p less than 0.0001) and CRP (p less than 0.01) in a cohort of 20 RA patients. The mean drop for both ESR and CRP was 46%. This effect lasted over a variable period up to 6 months. A survey of 50 published drug efficacy studies in RA revealed that, while 44 used ESR and 20 CRP as efficacy measures, 37 neither excluded nor recorded i-a steroid injections during the study. Steroid injections were excluded in 8 studies and recorded in 5, being used as an outcome measure in 2 of these. It is recommended that the frequency with which i-a injections are used in drug efficacy studies is reported and that they are avoided in the 3 months preceding an outcome measurement if ESR or CRP are being used as outcome measures.

Aged↗
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

Expression of intercellular adhesion molecule-1 (ICAM-1) on human thyroid cells lines correlated with their binding of lymphoblasts.

We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) by novel functional human thyroid cell lines (designated SGHTL). ICAM-1 is constitutively expressed and it is rapidly upregulated in response to each of the recombinant cytokines: gamma-interferon, interleukin-1 and tumour necrosis factor. This contrasts with the more slowly increased expression of major histocompatibility complex (MHC) class II antigens in response to gamma-interferon alone. We have also demonstrated binding of activated lymphocytes to SGHTL cells: this interaction is increased following treatment with these cytokines and is inhibited by monoclonal antibodies directed against ICAM-1 or lymphocyte function-associated antigen-1 (LFA-1) but not by antibodies against CD2 or MHC class II antigens. Hence, we conclude that the binding of lymphoblasts to human thyroid cells involves an LFA-1- and ICAM-1-dependent pathway as well as other basal and cytokine-inducible pathway(s). These do not appear to involve MHC class II antigens, CD2 or an LFA-1 ligand other than ICAM-1.

Antibodies, Monoclonal↗
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

An assessment of tenoxicam, a nonsteroidal anti-inflammatory drug of long half-life, in patients with impaired renal function suffering from osteoarthritis or rheumatoid arthritis.

Fifty-eight patients, aged 48-87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was measured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four % of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment.

Aged↗
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↗
PubMed1979

Diclofenac sodium (Voltarol) and indomethacin: a multicentre comparative study in rheumatoid arthritis and osteoarthritis.

A five-centre double-blind crossover trial of two two-week periods using diclofenac and indomethacin showed that both drug groups (51 patients) with rheumatoid arthritis responded similarly in relation to pain scores and morning stiffness. It was noted that the response was better in inpatients than in outpatients, despite differences in disease severity. In the osteoarthritis trial (58 patients) it was shown that neither drug significantly reduced resting pain, although both drugs were significantly better in reducing pain on movement; however, patient preference was for diclofenac. Three patients treated with indomethacin withdrew owing to side-effects, compared with one on diclofenac. A slight but significant decrease in haemoglobin levels was observed in both treatment groups with osteoarthritis, but this did not appear to be symptom-related.

Arthritis, Rheumatoid↗
PubMed1979

Diclofenac sodium (Voltarol): drug interactions and special studies.

Diclofenac (Voltarol) has no effect on carbohydrate metabolism, insulin levels or tolbutamide metabolism, nor does it enhance the effect of tolbutamide, biguanide or glibenclamide. Although it produces minimal increases in prothrombin and partial thromboplastin times in healthy volunteers, it does not significantly affect the individual clotting factors, nor does it, in patients, enhance the effect of acenocoumarol or phenprocoumon. Like many other other non-steroidal anti-inflammatory drugs, it increases platelet aggregation time. There is a pharmacokinetic interaction between aspirin and diclofenac. Two independent studies have shown that aspirin markedly reduces the bioavailability of diclofenac, as measured by "area under the curve". Furthermore, patients exhibiting aspirin sensitivity as bronchospasm are likely to react to diclofenac in the same manner. Finally, diclofenac, as tested using excretion of 51Cr labelled red cells, induces minimal gastrointestinal blood loss, significantly less so than aspirin or naproxen.

Adult↗
PubMed1979

A double-blind comparison of diclofenac sodium (Voltarol) and placebo in inpatients with rheumatoid arthritis.

This preliminary study compared placebo with diclofenac (50 mg, rising to 150 mg per day) in a crossover study for seven days in thirteen inpatients. Regardless of the marked overall effect of hospitalization, an additional effect of diclofenac on grip strength and p.i.p. joint swelling was demonstrated, as well as a significant reduction in pain and in analgesic requirements. In addition, an improved technique for assessing the effect of NSAI drugs on p.i.p. joint swelling is described.

Arthritis, Rheumatoid↗
PubMed1979

Diclofenac (Voltarol) in rheumatoid arthritis: a report of a double-blind trial.

A double-blind trial compared diclofenac with placebo in 44 outpatients. On from each group dropped out with dyspepsia, and one (placebo group) with ineffective treatment. Twenty completers received diclofenac. Dosage was one tablet (25 mg diclofenac) three times daily during the first week. In the second (final) week, most patients had four or six tablets. Diclofenac had significantly greater effect on pain, grip, morning stiffness, joint tenderness and swelling, and in comparison to previous treatments, even though the placebo group required significantly more rescue anaglesic. A few patients in each group had slight dyspepsia. One in the active and six in the placebo group complained of minor central nervous system symptoms. There were no serious side-effects. Haematological, biochemical and urinary analyses showed no clinically important changes. It is concluded that, in the short term, diclofenac (Voltarol) is effective in relieving the symptoms of inflammatory polyarthritis. It is well tolerated as placebo medication, and had no detrimental haematological or biochemical effects.

Arthritis, Rheumatoid↗
PubMed1979

Diclofenac sodium (Voltarol): a double-blind comparative study with ibuprofen in patients with rheumatoid arthritis.

A double-blind comparative trial in 60 patients, using diclofenac (Voltarol) and ibuprofen (Brufen), showed a considerable improvement in morning stiffness amongst females in the diclofenac group. However, no significant differences was noted between these two drugs in relation to pain score, articular index or proximal interphalangeal joint size. Analysis of withdrawals and side-effects suggests that while ibuprofen may be slightly better tolerated, it is also associated with significantly more withdrawals due to lack of effect. No significant change in laboratory studies was noted, except for a slight decrease in mean haemoglobin levels. The trialist noted that all of the drop-outs and side-effects reported came from one hospital out of the four participating; this was possibly due to differences in pre-trial drug therapy and to the hospital being in an urban, rather a rural, situation.

Adult↗
PubMed1977

Drug and non-drug factors influencing adverse reaction to pyrazoles.

Some of the factors influencing the likelihood of the appearance of adverse drug reactions in patients are identified and discussed. Ways of quantifying some of the risks of adverse reactions in different patients are demonstrated. It is pointed out that adverse reaction data can give valuable guidance for both day-to-day patient management and for the initiation or guidance of research projects. In this latter connection, this study highlights the difference in time of onset between aplastic anaemia and agranulocytosis, suggesting different mechanisms of reaction. The majority of adverse reactions occur during the first three weeks of treatment and it is during this time that patients must be most carefully supervised. The old patients should be watched with particular care. It is concluded that age, sex, disease being treated, length of treatment and even the geographical location where the patient lives, can affect the time, type, frequency and outcome of an adverse drug reaction.

Adult↗