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Biomedical subjects

R F Willkens

Publications and source records attributed to R F Willkens.

At least 37 records · Page 2Linked to original sources
PubMed1991

Prognostic staging for therapy of rheumatoid arthritis.

An attempt should be made to predict the most likely course of individual disease when a patient is first diagnosed as having rheumatoid arthritis (RA). Such a prediction can be called prognostic staging for therapy. While no specific marker will accomplish this accurately, the summation of demographic, genetic, historical, physical, laboratory, radiologic, and scanning data may be used to make a reasonable estimation of outcome. The use of immunogenetic typing is the newest technique that can help identify patients likely to develop more serious disease. Once patients are identified as having probable aggressive disease, that is, beyond stage I, combination therapy should be initiated. Goals of therapy should include the prevention and/or interference of progression of radiologic erosions, as well as functional improvement as measured by life-style and productivity.

Arthritis, Rheumatoid↗
PubMed1991

Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease.

We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation.

Adolescent↗
PubMed1991

Early undifferentiated connective tissue disease. II. The frequency of circulating antinuclear antibodies in patients with early rheumatic diseases.

The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM-1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses.

Antibodies, Antinuclear↗
PubMed1990

Resolve: methotrexate is the drug of choice after NSAIDs in rheumatoid arthritis.

This article, in favor of the resolution that methotrexate (MTX) is the drug of choice after nonsteroidal antiinflammatory treatment, develops the following four points. MTX is an effective treatment of rheumatoid arthritis. MTX is easy to administer and to monitor for effectiveness and safety. MTX has demonstrated a therapeutic to toxic ratio that exceeds that of other second-line antirheumatic drugs. MTX has the potential to impair disease progression.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Liver histology in patients receiving low dose pulse methotrexate for the treatment of rheumatoid arthritis.

The liver histology of 52 patients treated with intermittent low dose pulse methotrexate for rheumatoid arthritis was evaluated using a modification of the Roenigk grading system. Patients studied had had an average of 3.2 years of treatment or had received 1.7 g methotrexate. No patient had cirrhosis; 15 (29%) patients had evidence of mild fibrosis. Histological abnormalities were not predicted by liver function test changes, with the exception that hypoalbuminaemia occurred in 60% of those with grade IV (modified criteria) findings. The need for liver biopsy in patients with rheumatoid arthritis treated with methotrexate before two years or 1500 mg of treatment has not been established. Whether serial liver biopsies will be needed beyond this time has yet to be determined.

Adult↗
PubMed1990

An overview of the long-term safety experience of nabumetone.

Safety data have been gathered in US clinical trials of nabumetone on 1912 patients from August 1981 to May 1988. Dosing in the double-blind trials was 100 mg at bedtime, but in open-label trials patients could increase the dosage of nabumetone to 1500 or 2000 mg if required. Adverse experiences reported in the double-blind and open-label studies that were considered related to nabumetone treatment, or of unknown origin, occurred most commonly in two body systems: the body as a whole, and the digestive system. Incidence rates greater than 10% for adverse experiences categorised by preferred term occurred in the 'body as a whole' category for abdominal pain, and in the digestive system for diarrhoea and dyspepsia. Dosage increases to 2000 mg appeared to cause a dose-related increase in diarrhoea. In the long term studies, gastrointestinal ulcers have been confirmed in 13 (0.7%) patients. Hepatic and renal function was well preserved in patients treated with nabumetone. Overall, only 7 nabumetone-treated patients (0.4%) showed a marked elevation in both ALT (SGPT) and AST (SGOT). Two nabumetone-treated patients showed marked elevations in renal parameters, serum creatinine and blood urea nitrogen. Overall, nabumetone was well tolerated, and the adverse experience profile was clinically acceptable and presented no unusual or unexpected patterns.

Aged↗
PubMed1989

New perspectives of secondary and tertiary therapy for rheumatoid arthritis.

Rheumatoid arthritis continues to be recognised as a disorder with a variable prognosis, but recent studies have emphasised its potential for shortening life span. Epidemiological, genetic, and natural history studies have helped to identify patients who are at risk for the development of more aggressive disease earlier in their clinical course, and rheumatologists are willing to be more aggressive in their treatment now as their armamentarium expands. Earlier separation of drugs into anti-inflammatory and immunomodulatory agents becomes irrelevant as these concepts change and drugs fulfil both definitions. Sequences of therapy continue to be dictated by the potential of toxicity and generally follow rather than precede disease progression. The addition of several new agents to the algorithms of therapy against rheumatoid arthritis raises questions about their effects and place in therapeutic regimens, especially as concerns auranofin, sulphasalazine, methotrexate and cyclosporin. Combination therapy is currently at the end of the drug line, but the therapeutic horizon beckons with the potential of biological agents aimed at the restoration of immune balance.

Arthritis, Rheumatoid↗
PubMed1988

One-year experience in patients treated with auranofin following completion of a parallel, controlled trial comparing auranofin, gold sodium thiomalate, and placebo.

Following a 21-week double-blind trial that compared the effects of treatment with auranofin (AUR), gold sodium thiomalate, and placebo in 193 patients, 147 patients entered a 1-year, open-label study of treatment with AUR (6 mg/day). Results of this open-label study suggest that AUR has a long-term use profile similar to that of other slow-acting antirheumatic drugs. AUR appears to be capable of sustaining an initial response to gold sodium thiomalate. The withdrawal rate remains relatively high: Nearly half of the study patients had discontinued AUR by the end of 1 year.

Adolescent↗
PubMed1988

A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis.

One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37-week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.

Adolescent↗
PubMed1987

Rheumatoid arthritis: clinical considerations in diagnosis and management.

Advances in the understanding of the immune response, in immunogenetics, and in better identification of microbial agents that produce arthritis have made possible more accurate diagnosis of rheumatoid arthritis. Epidemiologic study of groups of rheumatoid patients and their response to therapy has provided a broader perspective of the disease's course and management. Therapy must be guided by the acute or chronic phase of the disease and must embrace chemical, psychologic, and physical modalities to achieve the goals of pain relief and the restoration of immune balance. Rheumatoid arthritis can no longer be considered benign since it impairs the duration as well as the quality of life. Therapy should be aggressive depending upon the predictors of more destructive disease.

Arthritis, Rheumatoid↗
PubMed1987

Lack of association between HLA-DR2 and clinical response to methotrexate in patients with rheumatoid arthritis.

Recent studies have indicated an association between the HLA-DR2 phenotype and substantial response to methrotrexate in patients with rheumatoid arthritis (RA). To further resolve this issue, we analyzed this relationship. Our data, obtained from a multicenter, double-blind study of rigorously assessed patients with RA, demonstrated that neither HLA-DR2 nor any other HLA-DR specificity is significantly associated with a substantial clinical response to methotrexate in patients with RA.

Arthritis, Rheumatoid↗
PubMed1987

Forefoot surgery in rheumatoid arthritis: subjective assessment of outcome.

Forefoot surgical outcomes were evaluated in 26 patients with rheumatoid arthritis. A total of 45 procedures were reviewed with emphasis on first ray intervention. Disease duration and aggressiveness of preceding medical therapy were combined to establish a disease severity index. Patients operated were predominantly in the midrange of disease severity. Subjective data on the relief of pain, callus, and deformity were favorable but this benefit was not long lasting inasmuch as patients were most satisfied in the period immediately following surgery and less so as time elapsed from intervention. Fusion of the first metatarsophalangeal joint seemed better than resection alone, indicating that stability should be the primary goal for surgical intervention of the rheumatoid forefoot.

Arthritis, Rheumatoid↗
PubMed1985

Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.

One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

Administration, Oral↗
PubMed1985

Pancytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis.

Low dose pulse MTX was associated with the development of pancytopenia in six patients with RA. Two patients died. Factors implicated in the occurrence of this complication were renal impairment in five patients, medication errors by two patients, preexisting marrow injury from occult alcoholism in one patient, and an apparent idiosyncratic reaction to the drug in another. Medication errors were associated with the use of five or more medications, and the unusual schedule of administration of low dose MTX may also have been contributory. From a consideration of the clinical pharmacokinetics of MTX, we suggest other factors that may predispose to the occurrence of marrow toxicity: the presence of hypoalbuminemia, interactions between MTX and other protein bound or weakly acidic drugs, and the repetitive dosing schedule of low dose MTX. Based on our experience, patients with impaired renal function (creatinine greater than or equal to 2.0 mg/dL) should not receive MTX. Renal function should be monitored regularly during treatment with MTX, and blood counts should be observed carefully if a new drug is added or substituted. A 5 mg test dose of MTX before initiating weekly therapy may identify patients with severe hypersensitivity to the drug. The potential risks of using MTX in a patient unwilling to accept blood products should be acknowledged and discussed with the patient. Furthermore, we recommend the use of leucovorin if pancytopenia occurs, even if low or undetectable serum levels of MTX are present.

Adult↗
PubMed1985

Worldwide clinical safety experience with diclofenac.

Data from more than 100,000 patients in foreign and United States trials provide substantial evidence of diclofenac's safety and tolerability. Adverse experiences were infrequent and generally mild or transient. In United States short-term trials, the frequency and severity of side effects compared favorably with rates for placebo, aspirin, and other NSAIDs. The drop-out rate for therapeutic reasons (adverse effects or lack of efficacy) was lower for diclofenac than for any of the comparative treatments. In long-term trials, diclofenac has been taken safely for a year or more. The incidence of adverse experiences reported for older patients (greater than or equal to 65 years) treated with diclofenac did not generally differ from that reported for younger patients. No significant differences in the incidence of hepatic problems were detected between diclofenac and other active treatments in U.S. trials. Finally, foreign post-marketing data on adverse experiences show that diclofenac is one of the safest agents of its kind for the treatment of a broad range of rheumatic conditions.

Aspirin↗
PubMed1985

Short term efficacy of methotrexate in the treatment of rheumatoid arthritis.

Methotrexate is easily administered, widely accepted by patients, and has a rapid therapeutic effect. With careful attention to known risk factors, such as alcoholism, diabetes, obesity, and renal disease, it is a useful agent for the treatment of refractory rheumatoid arthritis (RA). Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent. This paper will review the findings of the Cooperating Clinics of the American Rheumatism Association, as well as other studies that have investigated the short term efficacy of methotrexate.

Arthritis, Rheumatoid↗