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Biomedical subjects

J R Ward

Publications and source records attributed to J R Ward.

At least 55 records · Page 3Linked to original sources

Methotrexate therapy in rheumatoid arthritis: 2-year retrospective followup study.

Clinical and laboratory data in 124 patients with rheumatoid arthritis treated with methotrexate (MTX) were retrospectively reviewed over the initial 2 years after the start of treatment. Clinical improvement occurred in 103 (83%) patients after 12 weeks of treatment. At 2 years of followup, 60 patients (48%) continued to receive MTX with sustained clinical benefit. It has been discontinued in 64 (52%) patients (adverse drug reactions in 38, lack of clinical benefit in 15, and miscellaneous reasons in 11). Patients with adverse drug reactions had higher initial serum creatinine and blood urea nitrogen values than patients without adverse drug reactions.

Adult↗

Role of disease-modifying antirheumatic drugs versus cytotoxic agents in the therapy of rheumatoid arthritis.

Disease-modifying antirheumatic drugs are used to modify or alter the rheumatoid arthritis disease process. Disease-modifying antirheumatic drugs do not demonstrate the characteristic analgesic, antipyretic, and anti-inflammatory actions of the nonsteroidal anti-inflammatory drugs, since weeks or months of treatment are required before clinical benefit is observed. Although they have not been proved to delay, prevent, or reverse articular damage, therapy with disease-modifying antirheumatic drugs, when successful, is associated with decreased pain and joint swelling and improved function. Disease-modifying antirheumatic drugs and cytotoxic agents should not be considered as routine treatment for patients with rheumatoid arthritis. Before disease-modifying antirheumatic drug therapy is implemented, an optimal basic program of physical therapy, rest, and nonsteroidal anti-inflammatory drugs should be implemented, and it must be documented that the patient still has sufficient disease to justify the costs, risks, and benefits of these treatments. Drugs that are approved by the Food and Drug Administration (FDA) are preferred over nonapproved drugs. Hydroxychloroquine, parenteral gold salts, oral gold, D-penicillamine, and the cytotoxic drug azathioprine are the FDA-approved disease-modifying antirheumatic drugs for use in rheumatoid arthritis. Many, not all, rheumatologists would employ hydroxychloroquine as the first-choice disease-modifying antirheumatic drug in patients who have early, mild, and nonerosive disease; treatment should be continued for six months before being abandoned for lack of efficacy, and appropriate ophthalmologic examination every four to six months is indicated. An alternative would be auranofin, whose efficacy approaches that of parenteral gold, yet may be safer. For patients who have severe active rheumatoid arthritis, especially with erosive changes, parenteral gold salts are usually a first choice. D-penicillamine is also effective in controlling the signs and symptoms of rheumatoid arthritis, but serious toxicity may occur. Azathioprine might be considered a competitor to D-penicillamine, although the FDA approval restricts its use to patients who have failed gold therapy. Two cytotoxic drugs that are not FDA approved are methotrexate and cyclophosphamide. Methotrexate can be very effective, but its side effects, particularly pulmonary and hepatic, must be carefully monitored. Cyclophosphamide is generally considered too toxic for use in patients with rheumatoid arthritis, although it may be helpful in patients with systemic rheumatoid vasculitis or patients who have failed all other therapies.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents↗

Identification of degradation products of 2-chloroethyl ethyl sulfide by gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry under both electron impact and methane chemical ionization conditions has been used to detect impurities and degradation products present in the mustard simulant 2-chloroethyl ethyl sulfide, with a detection limit of 0.05 area percent. After one and two years of storage at ambient temperatures, the primary degradation product was 1,4-dithiane formed from the degradation of dimeric sulfonium ions. Oxidation and hydrolysis products were not detected.

Chemical Phenomena↗

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↗

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↗

Peripheral lymphocyte depletion in gold sodium thiomalate-treated rheumatoid arthritis patients.

It has been reported that gold sodium thiomalate treatment of rheumatoid arthritis reduces the number of peripheral blood lymphocytes. In a prospective, double-blind, randomized trial comparing gold sodium thiomalate, auranofin, and placebo in the treatment of rheumatoid arthritis, we investigated absolute lymphocyte counts. We found that peripheral lymphocyte counts decreased, but there was no correlation with clinical change in disease activity.

Arthritis, Rheumatoid↗

Arthritogenic effects of Mycoplasma arthritidis T cell mitogen in rats.

The intraarticular injection of Mycoplasma arthritidis T cell mitogen (MAM) produced significant joint swelling with inflammation in DA rats. Histologic examination of the joint initially showed edema below the synovial surface layer with light polymorphonuclear and focal lymphoid cell infiltration. Widespread but incomplete shedding of the surface layer of the synovial membrane and hypertrophy and hyperplasia of the subsynovium with fibroblasts and macrophages were observed subsequently. The hyperplastic process began to resolve by Day 5 and almost completely disappeared by Day 7 with healing of the surface layer, leaving virtually no trace of the preceding acute episode. Arthritis in animals with previous adjuvant induced arthritis was not exacerbated by the intraarticular injection of MAM.

Animals↗

Expression of metabolism-inhibition antibodies against Mycoplasma arthritidis in rats.

Shared antigens between Mycoplasma arthritidis and rat tissues may be responsible for the lack of metabolism-inhibition (MI) and other neutralizing antibodies in rats with M arthritidis-induced arthritis. We were not able to confirm such antigens or to detect cross-reacting antigens between M arthritidis and rat lymphocytes, thymocytes, and muscle tissue. Antisera of rabbit origin to rat lymphocytes, thymocytes, and skeletal muscle reacted by ELISA with M arthritidis only when the mycoplasmal antigens were prepared from organisms grown in medium containing horse serum. Such activity could be completely absorbed by horse serum. These antisera to rat tissues also failed to react by radioimmunoprecipitation with M arthritidis surface antigens. In addition, antibody activity against homologous antigens could not be absorbed by M arthritidis. Similarly, antisera of rabbit origin against M arthritidis failed to react by ELISA specifically with rat lymphocytes, thymocytes, and skeletal muscle or to react by radioimmunoprecipitation with 125I-labeled rat lymphocyte antigens. These rat tissues could not specifically absorb antibodies against M arthritidis from antisera of rabbit origin. These findings suggest that the lack of MI antibodies in rats probably can not be explained by rat tissue antigens that cross-react with M arthritidis MI antigens. Finally, antisera of rat origin against M arthritidis and other rat tissue components failed to block rabbit MI activity against M arthritidis, thus arguing against steric hindrance as a means of preventing recognition of MI antigens.

Animals↗

Low dose pulse methotrexate in rheumatoid arthritis: an 8-year experience with hepatotoxicity.

The clinical utility of standard liver function tests for monitoring low dose pulse methotrexate therapy is reviewed in 163 rheumatoid arthritis patients over an eight-year period. Abnormalities of hepatic enzymes were seen in 58% of patients but led to cessation of therapy in only 5%. Moderate alcohol intake did not affect the frequency of liver test abnormalities. Abnormalities were seen more frequently in patients with longer duration of methotrexate therapy and in those with higher total dose. There was no correlation between liver test abnormalities and day of serum sampling relative to day of methotrexate dosing, nor was a correlation seen between liver test abnormalities and total weekly dose of methotrexate. Methotrexate has been demonstrated to be an effective drug in the treatment of rheumatoid arthritis. The clinical utility of standard liver tests to predict the potential for hepatotoxicity is questionable.

Adult↗

Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate.

Methotrexate therapy has been effective in the treatment of RA with short term experience suggesting little serious adverse reactions. Our review of 168 patients receiving methotrexate has identified nine patients with probable or possible methotrexate-induced pulmonary toxicity, giving a prevalence of 5% and an incidence of 3.9 per 100 patients per year. No clinical or laboratory features showed an association that could potentially predict the development of pulmonary disease. All patients experienced complete recovery with supportive care and/or corticosteroid therapy. Clinical monitoring for this complication is warranted in all patients receiving long term methotrexate therapy for RA.

Adult↗

Quantitative solid phase fluorescence immunoassay of rheumatoid factor and C-reactive protein in active rheumatoid arthritis.

A quantitative, semiautomated, solid-phase fluorescence immunoassay (FIA) has been developed for measuring rheumatoid factor (RF) and C-reactive protein (CRP). The correlation of the FIA measurement of RF and CRP with standard measurements in rheumatoid arthritis (RA) patients is not known. To determine the correlation of FIA with standard assay methods, RF and CRP levels were measured by both methods in 151 patients with active RA. RF levels measured by FIA correlated very closely with charcoal agglutination method (r2 = 0.890, P less than 0.0001). CRP levels by FIA correlated very closely with CRP levels by nephelometric method (r2 = 0.886, P less than 0.0001) and Westergren erythrocyte sedimentation rates (ESR) (r2 = 0.356, P less than 0.0001). A weak statistical correlation of RF, CRP, and ESR with some clinical variables of RA disease activity was demonstrated. Measurement of RF and CRP by FIA is similar to standard methods and offers no specific advantages in evaluating RA patients at a single evaluation.

Arthritis, Rheumatoid↗

Diagnostic criteria in rheumatoid arthritis.

For rheumatoid arthritis (RA), criteria have been developed for classification of groups of patients in population surveys, selection for therapeutic trials, inter-institutional comparison of patients, evaluation of diagnostic trials, diagnosis of RA in individual patients, estimation of disease frequency, and assistance in determining prognosis. The American Rheumatism Association (ARA) "Criteria for the Classification of Rheumatoid Arthritis-Diagnostic Criteria for Rheumatoid Arthritis" were published in 1958 and have become a standard. These criteria are empiric and attempt to incorporate reasonable combinations of sensitivity and specificity. Despite the recognition that these criteria should be expected to change with improved knowledge, no further modification has been published. Other criteria such as the ARA "Proposed Criteria for Rheumatoid Arthritis" represent an important effort to encourage uniformity in definitions and use of the term remission. Yet it is well to remember that they have never been tested in prospective studies and are considered preliminary. The Co-operative Systematic Studies in Rheumatic Diseases, when studying slow-acting anti-rheumatic drugs, have chosen to use clinical endpoints such as 50% improvement in joint tenderness and swelling counts (or scores) rather than combined variables which include morning stiffness and changes in laboratory variables. This approach permits the true assessment of drug effects. In summary, current criteria have served us well. Nonetheless, we should not become complacent and should always question their sensitivity, specificity and application.

Arthritis, Rheumatoid↗

Communications bridges raise productivity, reduce stress.

In the health care professions, the results of miscommunication and misunderstanding can be costly. Stress-related ailments and burnout frequently occur. Managers therefore should examine organizational communication strategies and offer ways of dealing with stress, if necessary. One stress-reduction measure that can be undertaken at little cost is bridge building. The bridge-building process involves making a connection or link between people by careful listening and attention to their interactions with another. Bridge building may include persons from all organizational levels; the only limits are participants' willingness to risk and their desire to improve the work environment. One strategy for bridge building is the story meeting. Because stories are a representative way of addressing complex issues, they can provide a framework for handling sensitive situations. Creating a story about a department or work team allows persons to deal with inner frustrations in a nonthreatening way and to consider creative outcomes to their shared problem.

Communication↗

Slow-acting anti-rheumatic drug therapy for rheumatoid arthritis.

Rheumatoid arthritis is a disorder that frequently can be controlled with a program of physical therapy, rest and therapeutic doses of aspirin or another nonsteroidal anti-inflammatory medication. However, some patients' diseases are not controlled on this regimen. These patients are candidates for therapy with slow-acting anti-rheumatic drugs. This article discusses the indications for use of these medications as well as the potential benefits and adverse drug reactions commonly associated with their use.

Arthritis, Rheumatoid↗

Hematuria in patients with rheumatoid arthritis receiving gold and D-penicillamine.

We reviewed the urinalyses from 2 multicenter controlled randomized trials, one comparing moderate and low dose D-penicillamine to placebo and another comparing gold sodium thiomalate (GSTM), auranofin (AF) and placebo. In the D-penicillamine trial 30% of the 40 patients taking placebo, 34% of the 70 patients receiving 125 mg/day of D-penicillamine and 31% of the 61 patients receiving 500 mg of D-penicillamine had recurrent hematuria. In the GSTM/AF trial, 35% of the 43 placebo treated patients, 35% of the 54 GSTM treated patients and 30% of the 64 AF treated patients had hematuria. No significant difference in the frequency of hematuria between the groups in either trial was apparent. These findings suggest that the traditionally held belief that gold and D-penicillamine cause hematuria should be reconsidered.

Adult↗

Effects of weekly and daily pretreatment with gold sodium thiomalate on adjuvant induced arthritis.

The effect of gold sodium thiomalate on adjuvant induced arthritis in DA rats was investigated. Ten mg/kg gold given in either weekly or daily injections before the administration of adjuvant was able to decrease the severity of arthritis in these animals. One mg/kg gold given as daily injections had no effect on adjuvant induced arthritis. One mg/kg gold given as weekly injections before adjuvant administration reduced the severity of arthritis to a level which was intermediate between that seen in the placebo control and the 10 mg/kg gold groups. The proliferative responses of spleen cells to mitogens in these animals were not altered by in vivo gold therapy.

Animals↗

Efficacy of diclofenac in osteoarthritis. Experience in the United States.

The role of diclofenac sodium in patients with symptomatic osteoarthritis of the hip or knee has been evaluated in five prospective, randomized, double-blind, controlled trials with placebo, aspirin, and naproxen conducted in the United States. The objectives were to evaluate efficacy, tolerability, and safety. In these trials, diclofenac, 100 or 150 mg daily, was more effective than aspirin, 2.4 or 3.6 g daily, and as effective as naproxen, 500 mg daily. In individual trials, there were no statistically significant differences in the incidence of adverse effects between treatment groups. For all trials combined, the dropout rate due to adverse effects was similar for each treatment group. The dropout rate because of an unsatisfactory response was lowest for patients treated with diclofenac.

Adult↗