Biomedical subjects

J R Ward

Publications and source records attributed to J R Ward.

At least 73 records · Page 4Linked to original sources

PubMed1986

Role of non-RT1 genes in the response of rat lymphocytes to Mycoplasma arthritidis T cell mitogen, concanavalin A and phytohemagglutinin.

A comparison of splenic cells from various inbred rat strains indicated that DA, Lewis, Buffalo, August, Wistar Furth, and (LEW X BN)F1 all responded well to the Mycoplasma arthritidis T cell mitogen, phytohemagglutinin and concanavalin A, but cells from BN and MAXX rats were very weakly or nonresponsive. Cells from congenic strains expressing nonresponder background genes, and responder haplotypes at RT1 (BN.1L(LEW), RT1; BN.1A(DA), RT1av1) failed to respond significantly to the mitogens. Rats expressing responder background genes but the nonresponder haplotype at RT1 at RT1 (WF.1N-(MAXX), RT1n) exhibited high responses to all mitogens. The controlling role of non-RT1 genes was confirmed by testing tissue-typed (DA X BN)F2 progeny and (DA X BN)F1 X DA and (DA X BN)F1 X BN progeny. No association was seen between the expression of a/a, a/n, or n/n at RT1 and the degree of response to the mitogens. In contrast, as the proportion of DA non-RT1 genes increased, so did the degree of mitogenic responsiveness. Similar results were obtained by using a partially purified preparation of the mycoplasma T cell mitogen. The results indicated that in the (DA X BN)F1 hybrids, responsiveness to all mitogens was recessive: this contrasts with the (LEW X BN)F1 hybrids in which responsiveness was dominant. Finally, we showed that both responder and nonresponder splenic cells were capable of binding the M. arthritidis mitogen. The data contrast with those obtained with nonresponder mouse strains the cells of which failed to bind mitogen due to the absence of the E alpha chain of the I-E-coded molecule.

Animals↗

PubMed1986

Differential effects of in vitro gold sodium thiomalate on the stimulation of human peripheral blood mononuclear cells by Mycoplasma arthritidis T cell mitogen, concanavalin A and phytohemagglutinin.

The effects of in vitro gold sodium thiomalate (GSTM) on peripheral blood mononuclear cells (PBM) stimulated by a Mycoplasma arthritidis T cell mitogen (MAM), concanavalin A (Con A), and phytohemagglutinin (PHA) were compared in 5 individuals by measuring 3H-thymidine uptake by PBM. The MAM induced lymphocyte transformations were more significantly inhibited by in vitro GSTM than parallel assays using Con A and PHA. The effects could not be explained by differences in cell viability, length of cell culture, mitogen concentration, and level of mitogen stimulation, suggesting that MAM may be a useful probe in evaluating the effects of GSTM on immune function.

Cell Division↗

PubMed1986

Chrysiasis: the role of sun exposure in dermal hyperpigmentation secondary to gold therapy.

To investigate the role of sun exposure in the pathophysiology of chrysiasis, we studied 10 Caucasian female patients with rheumatoid arthritis: 4 with clinically apparent chrysiasis and 6 without apparent pigmentation. Three patients without chrysiasis had received over 4 g of gold and 3 less than one g. The mean melanin score, determined by histological examination of sun exposed and nonsun exposed skin, was significantly higher in the sun exposed skin of the chrysiasis and high dose controls than low dose controls (p less than .05). Concentration of gold measured semiquantitatively by transmission electron microscopy and quantitatively by atomic absorption showed increased gold concentration in sun exposed when compared to nonsun exposed skin of chrysiasis and high dose controls (p = .26). Low dose controls had no gold demonstrated by either method. Our results suggest that gold deposition in the dermis stimulates melain production and that melanin is important in hyperpigmentation of chrysiasis. Furthermore ultraviolet light may induce preferential uptake of gold by the skin.

Arthritis, Rheumatoid↗

PubMed1986

Circulating HLA-DR bearing T cells: correlation with genetic rather than clinical variables.

Elevated levels of circulating HLA-DR bearing (activated) T cells have been reported in a variety of conditions. The role played by these cells in the pathogenesis of disease is not established. We found elevated levels of activated T lymphocytes in patients with rheumatoid arthritis (RA), dermatitis herpetiformis, gluten sensitive enteropathy, as well as presumed healthy persons with HLA-B8 antigen. We could not show any change in the concentration of these cells with disease activity, therapy, or in a case of dermatitis herpetiformis, challenge with the presumed antigen, gluten. Our studies do not suggest an apparent causal relationship between activated T lymphocytes and the above disorders.

Arthritis, Rheumatoid↗

PubMed1985

Characterization of T cells bearing HLA-DR antigens in rheumatoid arthritis.

It has been demonstrated that T cells bearing HLA-DR antigens on their surface are actively involved in an immune response. In diseases of disordered immunoregulation, including rheumatoid arthritis (RA), there are elevated numbers of circulating HLA-DR+ T cells. In this study, we examined the cellular physiology of these T cells in RA patients. Using tritiated thymidine incorporation, we found that, in most patients, HLA-DR+ cells do not account for a significant amount of spontaneous proliferation found in peripheral blood T cells. RNA hybridization studies, using a cloned HLA-DR alpha chain gene probe, indicate that the T cells actively synthesize HLA-DR antigens rather than passively adsorbing them. The cell surface phenotype of the HLA-DR+ T cells was analyzed using double immunofluorescence and a variety of monoclonal antibodies. The expression of T cell differentiation antigens T4, T6, T8, and T10 varied markedly from patient to patient. In some patients, a significant number of cells expressed both T4 and T8 antigens. Most HLA-DR+ cells also express antigens defined by the following antibodies: anti-Tac (the interleukin-2 receptor), J2 (a glycoprotein found on T cell blasts), and ILR-1 (a class II major histocompatibility complex antigen). Activated T cells bearing HLA-DR antigens may play a role in the development of RA. Our data demonstrate that although these cells are not lymphoblasts, they possess a distinct cell surface phenotype.

Antigens, Surface↗

PubMed1985

Reduced joint count indices in the evaluation of rheumatoid arthritis.

Two types of summary measures of joint disease were evaluated in 2 controlled clinical trials in rheumatoid arthritis patients. One measure was based solely on the clinical/biologic judgment approach; the other combined this methodology with statistical approaches using reliability and factor analyses. "Signal joint" indices, summarizing disease activity in 2-5 key joints, were found to be insensitive to deterioriation of nonsignal joints. Therefore, they are not recommended as replacements for the complete articular survey in rheumatoid arthritis. A reduced version of the complete articular survey was found to be desirable based on its validity, reliability, accuracy, precision, and sensitivity to active drugs. Its sensitivity can be slightly higher or lower than that of the full joint survey.

Arthritis, Rheumatoid↗

PubMed1985

Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

Adult↗

PubMed1985

Uses and abuses of analysis of covariance in clinical trials.

Measurement of improvement in clinical trials in chronic diseases commonly compares baseline data to endpoint values by performing t-tests or analysis of variance (ANOVA) on raw gains or percentage changes. This procedure can be misleading and the use of an analysis of covariance (ANCOVA) should be considered. Properly used, ANCOVA increases statistical power in a clinical trial. However, its advantage over t-tests can be nullified by small numbers of patients, violations of assumptions, and incorrect application of the techniques. An evaluation of ANCOVA in chronic disease studies is given, with examples of its strengths and weaknesses as seen in several drug trials in the rheumatic diseases. Recommendations on its use and a decision tree for the nonstatistician are provided.

Analysis of Variance↗

PubMed1985

Circulating immune complexes containing secretory IgA in jejunoileal bypass disease.

Thirteen patients were studied after jejunoileal bypass (JIB) surgery. Seven developed arthritis and six did not. Circulating immune complexes containing IgG and IgA were detected in the sera of patients with and without arthritis. IgA complexes were shown to contain secretory component, a protein predominantly associated with intraluminal IgA, in significantly higher levels in patients with arthritis. Analytical ultracentrifugation showed complexes of approximately 10 X 8S, consistent with the size of secretory IgA. Arthritis after JIB appears to be associated with circulating immune complexes containing secretory IgA.

Acute Disease↗

PubMed1985

Methotrexate and the liver.

The findings of liver studies in 29 patients who were treated with low dose pulse methotrexate for rheumatoid arthritis (RA) are described. The biopsy specimens of 22 patients (76%) showed liver abnormalities, but cirrhosis did not develop in any patient. There were no statistically significant differences in age, duration of treatment, or cumulative dose between patients in whom abnormal liver histology developed and those in whom it did not. Our findings showed that isolated elevations of the aminotransferase enzymes or alkaline phosphatase levels did not predict liver disease, nor did the absence of elevation of these enzymes assure the absence of liver disease. Serial elevations of the aminotransferase and/or alkaline phosphatase enzyme levels and the development of hypoalbuminemia during treatment were specific indicators of the development of liver disease. In the patients studied, significant liver disease did not develop before 2 years of therapy or with a cumulative dose of methotrexate of less than 1500 mg.

Adult↗

PubMed1985

Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis.

Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis. By 1972, low dose pulse methotrexate was observed to be useful in RA, but it was not until 1980 that additional beneficial effects of methotrexate in the treatment of patients with refractory RA appeared in the literature. Subsequently, both uncontrolled experience and double blind prospective trials have demonstrated efficacy and acceptable tolerability and safety of methotrexate in the treatment of patients with RA. Guidelines for its use in patients with RA still need to be developed.

Adult↗

PubMed1985

Arthrocentesis.

Aspiration of the synovial joints is an important part of the diagnostic and therapeutic armamentarium of the physician and may provide vital information that can be obtained in no other way. As with any other technique in medicine, skill and safety in the aspiration of joints can be acquired only through careful study and continued practice in arthrocentesis. When appropriate preparations and precautions are observed, obtaining fluid from synovial joints is safe, relatively pain free, inexpensive, and extremely beneficial to the patient.

Ankle Joint↗

PubMed1985

'Pseudoseptic' arthritis in patients with rheumatoid arthritis.

It is generally recognized that patients with rheumatoid arthritis are at greater risk than the general population for the development of bacterial joint infection. It is not usually appreciated, however, that such patients may present with a clinical syndrome that mimics septic arthritis in most respects except that all cultures are consistently negative and antibiotics are not essential for treatment. We report our experience with five cases of "pseudoseptic" arthritis in patients with rheumatoid arthritis and suggest an approach for management.

Adult↗

PubMed1984

Update on ibuprofen for rheumatoid arthritis.

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

Anti-Inflammatory Agents↗

PubMed1984

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↗

PubMed1984

Susceptibility and resistance to 6-sulfanilamidoindazole-induced arthritis among inbred strains of rats.

Inflammation induced by 6- sulfanilamidoindazole (6-SAI) in aged, outbred rats is predictably produced, but the pathogenesis is not understood. We demonstrate the variable resistance of 15 inbred rat strains to 6-SAI arthritis. Susceptibility to 6-SAI arthritis is not directly linked to the major histocompatibility complex, although resistance is related to the major histocompatibility complex in other experimental forms of rat arthritis. The genetic background of these inbred rat strains appears to have a major role in 6-SAI arthritis susceptibility.

Animals↗

PubMed1984

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↗

PubMed1984

Auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. Cooperative systematic studies of rheumatic diseases.

Two hundred eight patients were studied in a prospective, controlled, double-blind multicenter trial comparing auranofin (AUR), gold sodium thiomalate (GST), and placebo. One hundred sixty-one patients completed at least 20 weeks of therapy. Response to a variety of measures of efficacy was generally modest for both gold treatment groups although improvement was continuing in both groups at the end of the study. There was statistically significant improvement with both gold preparations compared to placebo for the number of tender joints, the joint tenderness score, and physician assessment of disease severity. GST was also significantly better than placebo for the joint swelling score. GST demonstrated more improvement in patients with anemia and thrombocytosis compared to the other treatment groups and both gold preparations were superior to placebo in improvement of an elevated erythrocyte sedimentation rate. Twenty-seven percent of patients on GST were withdrawn from the study for adverse drug reaction with rash and stomatitis being the predominant cause. Only 6% of patients on AUR were withdrawn for untoward drug effect. The time of onset of the adverse reactions is discussed. The two gold preparations were similar in efficacy although AUR was better tolerated.

Anti-Inflammatory Agents↗