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Biomedical subjects

P D Fowler

Publications and source records attributed to P D Fowler.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1985

Osmosin: its effect on plasma and synovial fluid kinetics of indomethacin.

'Osmosin' (sodium indomethacin trihydrate, now withdrawn) produced a constant rate of release of indomethacin into the gut. Paired plasma and synovial fluid samples were obtained at regular intervals following a single dose of 'Osmosin' (19 patients) and after continuous daily dosing (15 patients). Indomethacin is rapidly absorbed and plasma concentrations maintained in the range 0.3 to 0.6 micrograms/ml after the first 4 h. Equilibrium between plasma and synovial fluid occurs, with SF/plasma ratios 0.74 to 0.82 12-24 h after a single dose and up to 0.96 thereafter. The indomethacin synovial fluid/plasma profile is changed by Osmosin from the pattern of a short half-life drug to the pattern typical of a long half-life drug. Results from serial samples obtained by use of indwelling cannulae (in vein and knee joint) show close agreement with our single paired sampling technique. Our method may have theoretical disadvantages but it has many practical advantages.

Adult↗
PubMed1985

Anti-rheumatic drugs and joint damage in rheumatoid arthritis.

The effect of second-line anti-rheumatic drugs such as gold on the course and progression of joint damage has been the subject of considerable controversy. We have evaluated the effects of second-line anti-rheumatic drugs in three studies of 46-84 patients with rheumatoid arthritis given a second-line drug continuously for 12 months. Using two different methods of radiographic assessment we found that there was significant progression over the 12-month period when the mean changes in the groups of patients were examined, and there was similar indications of continuing disease activity shown by mean values of acute phase proteins and ESR which were above the normal range at both six and 12 months. But there were subgroups of patients who showed a reduction in ESR and joint tenderness with a related slowing of the rate of radiographic progression in the second six months of treatment. There was no direct relationship between changes in the ESR and radiographic progression in individual patients. Although anti-rheumatic drugs are not ideal and therapy does not cause remission in many patients, some patients respond well. Rheumatoid arthritis may represent a heterogeneous collection of patients who respond individually to different drugs.

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

A phenylbutazone dose-finding study in rheumatoid arthritis.

Different doses of phenylbutazone have been compared in a double blind study on 32 patients with rheumatoid arthritis in order to determine the minimum effective dose. Of 8 different dose levels studied (90 mg, 150 mg, 180 mg, 240 mg, 270 mg, 300 mg, 360 mg and 450 mg/day) the most efficacious was found to be 300 mg/day. Doses below this did not produce full benefit; no further improvement occurs with higher doses. Although 7/32 patients developed adverse reactions there was no relationship between these and the plasma levels of either phenylbutazone or oxyphenbutazone. An attempt was made to distinguish 'responders' from 'non-responders'. We found no relationship between response and plasma levels of phenylbutazone or oxyphenbutazone.

Adult↗
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↗
PubMed1982

The pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease.

Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.

Administration, Oral↗
PubMed1982

The run-in period in trial design: a comparison of two non-steroidal anti-inflammatory agents in psoriatic arthropathy.

Psoriatic arthropathy is a relatively uncommon arthritis that exists in a wide variety of clinical forms. These two features of the disease cause problems in the design of clinical trials. In a comparison of two non-steroidal anti-inflammatory agents in this condition we attempted to overcome the difficulties by using a run-in period during which the dosage of one of the trial drugs was adjusted to suit the individual patient. After two weeks on indomethacin (75 mg or 150 mg/day) patients were allocated to four-week periods of indomethacin in the chosen dosage or diclofenac (75 mg or 150 mg/day) in a double-blind randomized crossover trial that used double dummy packaging. Of the 35 patients that entered the study, 19 completed both study groups. No significant differences were observed between the clinical improvements due to both drugs during the course of the study. In general more side-effects were seen during indomethacin treatment, though the study design precluded exact comparison. In a study biased against diclofenac, patient preference was 9/19 for indomethacin, 4/19 for diclofenac and 7/19 expressing no choice. Advantages and disadvantages of the study design are discussed.

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↗