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Biomedical subjects

R F Willkens

Publications and source records attributed to R F Willkens.

At least 55 records · Page 3Linked to original sources

Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis.

Thirty-seven patients with psoriatic arthritis were entered into a 12-week prospective, controlled, double-blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5-5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate-treated patients. No patients were withdrawn from the study for adverse drug effects.

Adult↗

Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold.

Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.

Arthritis, Rheumatoid↗

Outcome assessment in clinical trials. Evidence for the sensitivity of a health status measure.

Health status measures are conceptually relevant to the assessment of clinical outcome in the rheumatic diseases, but their ability to detect meaningful changes in health has not been clearly demonstrated. This report describes the performance of a self-administered health status questionnaire in a randomized, double-blind, 21-week comparison of placebo, oral gold, and injectable gold in rheumatoid arthritis patients. Outcome was assessed by standard clinical measures, including joint count, grip strength, and laboratory tests, and by the Arthritis Impact Measurement Scales, a reliable and valid health status measure that assesses physical disability, psychological status, and pain. Data from the clinical and health status measures produced highly similar conclusions: injectable and oral gold are more effective than placebo for rheumatoid arthritis, and injections are slightly more effective than oral gold. The health status measure was thus quite sensitive to clinically meaningful drug-induced improvements. These findings provide justification for the further application of health status measures to clinical trials of chronic disease.

Chronic Disease↗

Reappraisal of the use of methotrexate in rheumatic disease.

Methotrexate has been available for clinical use since 1951. Initially, it was utilized as a chemotherapeutic agent, but it has since been widely used in the treatment of such nonmalignant disorders as psoriasis and, more recently, experimentally in psoriatic arthritis and polymyositis. Its mechanism of action is imprecisely understood but it appears to involve both anti-inflammatory and immunosuppressive effects. Controlled pilot studies are underway using methotrexate in patients with severe rheumatoid arthritis.

Absorption↗

Free fatty acids in the pancreatitic arthritis syndrome.

Fat necrosis and arthritis occur in some individuals with pancreatitis. The intraarticular free fatty acid concentration was found to be markedly elevated in 2 patients with this pancreatitic arthritis syndrome. Injection of free fatty acids into rabbit knees reproduced the inflammatory synovial response including intracellular fat globules within leukocytes. Free fatty acids exceeding the available binding sites of albumin appear to mediate the extrapancreatic inflammatory manifestations of this syndrome.

Aged↗

Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.

A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, "nitritoid" reactions, and "gold pneumonitis" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.

Adolescent↗

Long-term clinical evaluation of suprofen and aspirin in patients with osteoarthritis.

The safety and efficacy of suprofen 200 mg q.i.d. and aspirin 650 mg q.i.d. in the treatment of chronic pain due to osteoarthritis were compared in a double-blind, randomized, parallel group study over a 12-week period. Suprofen was comparable to aspirin in the relief of pain and improvement in activity impairment. Results of ocular examination, laboratory data, and vital signs examinations indicated no clinically significant changes for suprofen. No serious side effects were reported by either group.

Aspirin↗

HLA antigens in Yakima Indians with rheumatoid arthritis. Lack of association with HLA-Dw4 and HLA-DR4.

Women of the Yakima Indian Nation, a northwest Native American population, are known to have an increased prevalence of a rheumatoid arthritis-like disease characterized by erosive arthritis, frequent involvement of metacarpophalangeal and wrist joints, and positive rheumatoid factor. These patients are frequently positive for antinuclear antibodies and often demonstrate adverse reactions to gold therapy. HLA antigens were determined for 29 Yakima Indians with this disease, but there was no increased frequency of either HLA-Dw4 or HLA-DR4, in contrast to other populations with rheumatoid arthritis. There was, however, a trend toward an increase in HLA-B40 and a decrease in HLA-DR8. The relative risk for rheumatoid arthritis in Yakima Indians was 2.53 in the presence of B40 and 0.28 in the presence of DR8.

Arthritis, Rheumatoid↗

Methotrexate: a perspective of its use in the treatment of rheumatic diseases.

MTX has been available for clinical use since 1951, and although it is widely accepted as a chemotherapeutic agent, its use in nonmalignant disorders has been sporadic and not well documented. Its mechanism of action is imprecisely understood but appears to involve both anti-inflammatory and immunosuppressive effects. The most extensive use of MTX in benign conditions has been in the treatment of psoriasis and more recently in psoriatic arthritis as well as polymyositis, sarcoid, and Reiter's syndrome. In addition, pilot studies have been carried out using MTX in patients with resistive RA. We have used MTX in 67 patients with severe RA. Maintained on oral pulse treatment schedule at 7.5 to 15.0 mg/week, approximately 75% had an improved global response with a significant decrease in active joints and ESR. Thirty-three patients have remained on therapy for periods of less than 1 year to more than 10 years. Thirty-four have discontinued treatment: 11 because of inefficacy, five with gastrointestinal complaints, three because of liver function abnormalities, and eight because of apprehension. Two patients died of neoplasm. Of the potential side effects of this agent, hepatotoxicity remains a serious consideration. We treat with attention to risk factors and rely on liver function tests to alert us to increased risk. There are data to suggest that a cumulative dose of MTX beyond 1.5 gm needs tissue surveillance. MTX appears to provide safe and effective treatment in resistive RA but requires further definitive trails.

Arthritis, Rheumatoid↗

Reiter's syndrome. Evaluation of preliminary criteria for definite disease.

A retrospective evaluation of 83 patients with Reiter's syndrome (RS) and 166 comparison arthritis patients was conducted in order to assess the preliminary criteria for definite RS. Data analysis was based on the statement that Reiter's syndrome consists of an episode of peripheral arthritis of more than 1 month duration occurring in association with urethritis and/or cervicitis. During the initial episode of RS, 70 of the 83 RS patients satisfied the criteria, yielding a sensitivity of 84.3%.

Arthritis↗

Sodium meclofenamate ('Meclomen') in the treatment of rheumatoid arthritis: a double-blind comparison with aspirin and placebo.

The therapeutic efficacy of sodium meclofenamate (300 mg per day) was compared with that of aspirin (3.6 g per day) and placebo in 317 patients with active rheumatoid arthritis. The 8-week double-blind treatment period was preceded by a 2-week washout period on aspirin. A smaller proportion of patients on sodium meclofenamate (11%) withdrew for a lack of efficacy than did patients on aspirin (18%) or placebo (40%). Analyses of measures of tenderness, total joint involvement, duration of morning stiffness, and patient condition and global improvement revealed that the therapeutic effectiveness of 300 mg sodium meclofenamate daily and 3.6 g aspirin daily were equivalent and significantly superior to that of placebo. The principal adverse reactions with sodium meclofenamate were gastro-intestinal symptoms of which diarrhoea was the most frequently reported. The rates of adverse reaction withdrawals were similar in the three treatment groups. Sodium meclofenamate showed good control of disease activity and was generally well tolerated in the treatment of rheumatoid arthritis.

Adolescent↗

Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma.

Lymph nodes obtained from 9 patients with active rheumatoid arthritis were stained by immunological techniques permitting identification of B and T cell areas within the nodes. The lymph nodes were also compared with those obtained from patients with lymphoma. The rheumatoid lymph nodes showed prominent B cell staining in the follicular centres by the EAC and fluoresceinated immunoglobulin techniques. Interfollicular areas were intensely stained with anti-theta globulin. In contrast, lymphoma nodes stained less intensely with fluoresceinated immunoglobulins but stained like benign nodes with EAC. The difference in staining may reflect the degree of disorganisation of the neoplastic follicle and/or the different sensitivity of these 2 methods in the detection of B cells. The differences in staining are helpful in distinguishing the benign changes associated with chronic inflammation from neoplastic B cell proliferative changes seen in lymph nodes.

Arthritis, Rheumatoid↗

Crossover comparison of benoxaprofen and naproxen in rheumatoid arthritis.

This multicenter double-blind clinical trial compared the efficacy and safety of benoxaprofen and naproxen in the treatment of rheumatoid arthritis. The studies followed a crossover design which provided 6 wk therapy with each of the 2 study drugs. Benoxaprofen at a single daily dose of 600 mg compared favorably to naproxen, 750 mg, administered in 2 equally divided doses. All efficacy results indicated slightly more improvement with benoxaprofen although the difference between the 2 drugs was not significant. Side effects were generally mild and only 1 patient discontinued benoxaprofen therapy because of a reactivation of a duodenal ulcer.

Adult↗