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Biomedical subjects

J R Ward

Publications and source records attributed to J R Ward.

At least 37 records · Page 2Linked to original sources
PubMed1993

Radiographic assessment of disease progression in rheumatoid arthritis patients enrolled in the cooperative systematic studies of the rheumatic diseases program randomized clinical trial of methotrexate, auranofin, or a combination of the two.

OBJECTIVE: To determine the radiographic progression of disease in rheumatoid arthritis (RA) patients from the Cooperative Systematic Studies of the Rheumatic Diseases clinical trial of auranofin (AUR) versus methotrexate (MTX) versus a combination of the two. METHODS: Baseline (week-0) and study-end (week-48) hand/wrist radiographs in 200 of the 211 patients who completed this multicenter trial (95%) were scored blindly by 2 readers for the presence of erosions and joint space narrowing (JSN). Both intraobserver reliability and interobserver reliability were 0.80 for erosions (P < or = 0.001); intraobserver reliability and interobserver reliability were both 0.75 for JSN (P < or = 0.001). RESULTS: Worsening erosion and JSN scores occurred in all 3 treatment groups, but the difference from baseline reached significance only in the AUR group. CONCLUSION: Clinical improvement has been clearly documented in all 3 treatment groups in this trial. Radiographic deterioration occurs in RA even when clinical features improve, but progression of disease as determined radiographically may be slowed by treatment with MTX.

Adult↗
PubMed1993

The effect of long-term methotrexate therapy on hepatic fibrosis in rheumatoid arthritis.

OBJECTIVE: To evaluate the progression of hepatic fibrosis in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). METHODS: Fifteen patients receiving MTX for RA were prospectively studied by electron microscopic analysis of biopsy specimens. RESULTS: Five of the 15 patients had evidence of increased hepatic collagen after 2 years of MTX therapy. CONCLUSION: Hepatic fibrosis may progress in a subgroup of RA patients treated with MTX.

Arthritis, Rheumatoid↗
PubMed1993

A long-range restriction map of human chromosome 5q21-q23.

A long-range restriction map encompassing the APC (adenomatous polyposis coli) gene has been constructed. The map includes 35 DNA markers and consists of two segments of 10 and 2.5 Mb. Published genetic markers have been connected using additional, nonpolymorphic DNA probes. The map clarifies marker order and allows comparison of physical and genetic data.

Adenomatous Polyposis Coli↗
PubMed1993

Effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis in rats.

The prophylactic and therapeutic effects of gold sodium thiomalate, cyclosporin A, cyclophosphamide, and placebo on collagen-induced arthritis (CIA) were evaluated in DA rats. Prophylactic treatment with cyclosporin A and cyclophosphamide suppressed the arthritis incidence, clinical inflammation, destructive bone changes, and development of anti-collagen antibody in DA rats subsequently injected with porcine type-II collagen. Therapeutic treatment with cyclosporin A and cyclophosphamide had a definite suppression on established CIA when started 21 days after the initial collagen injection, but the suppression was less marked than that of prophylactic treatment. Gold had no impact on CIA in DA rats when administered either prophylactically or therapeutically.

Animals↗
PubMed1992

Yeast artificial chromosomes for the molecular analysis of the familial polyposis APC gene region.

Two yeast artificial chromosomes (YACs) spanning a total distance of 1.1 megabase pairs of DNA around the MCC (for mutated in colorectal carcinoma) and APC (for adenomatous polyposis coli) genes at 5q21 have been isolated and characterized. Starting from the MCC gene, a strategy was undertaken to identify constitutional submicroscopic deletions in familial adenomatous polyposis patients that might considerably narrow down the position of the APC gene. To this end, YACs identified by the MCC gene were screened across a chromosome 5-specific cosmid library to provide a source of DNA probes for genomic scanning. The cosmids isolated from these experiments were used to screen a panel of somatic cell hybrids containing chromosome 5 segregated from patients suspected to carry putative interstitial deletions. This screening approach led to the confirmation of a small heterozygous deletion in a polyposis patient that overlaps one of the two isolated YACs. This YAC has been shown to contain the entire APC gene, in addition to a significant portion of DNA flanking the 5' end of the gene, and should therefore prove a valuable resource for functional studies by transfer to colorectal tumor-derived cell lines.

Adenomatous Polyposis Coli↗
PubMed1992

Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.

OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study.

Adolescent↗
PubMed1992

Serum hormone and metabolite concentrations in fasted young bulls and steers.

The effect of dietary energy restriction on serum insulin, insulin-like growth factor I (IGF-I), growth hormone, (GH), cortisol, plasma urea nitrogen (PUN) and nonesterified fatty acid (NEFA) concentrations was examined. Angus bulls and steers (10 mo) were allotted to two groups of 12 animals and assigned a treatment order. In a switchback design, animals in order 1 were fed a high grain diet, then fasted, while order 2 animals were fasted, and then fed. Animals were allowed 60 hr to acclimate between treatments. Serum and plasma were obtained at 20 min intervals and 60 min, respectively, for 6 hr after feeding and for the last 6 hr of a 30 hr fast. Serum was assayed for insulin, IGF-I, GH, and cortisol (total and free). Plasma was assayed for PUN and NEFA. Mean insulin (ng/ml) differed between fed (.95 +/- .08) and fasted (.26 +/- .08) animals (P less than 01). Both mean total and free cortisol (ng/ml) were lower in fed (11.48 +/- .99) (1.06 +/- .12) than in fasted (17.10 +/- .93) (1.62 +/- .12) animals, respectively (P less than .01). Animals in order 1 differed in mean IGF-I (ng/ml) between fed (199.0 +/- 8.0) and fasted (116.5 +/- 7.2) treatments (P less than .01). Mean IGF-I for animals in order 2 was 146.7 +/- 7.2 in fed and 213.9 +/- 7.2 in fasted animals (P less than .01). Mean GH did not differ between treatments. Mean PUN and NEFA were higher in fasted than in fed animals (P less than .01). Except for % free cortisol (P less than .05), the hormones did not differ between bulls and steers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. The Cooperative Systematic Studies of Rheumatic Diseases Group.

A composite index for estimating improvement in individual rheumatoid arthritis (RA) patients during trials of slow-acting, disease-modifying antirheumatic drugs (DMARDs) was developed by analyzing the responses of 130 placebo-treated participants in Cooperative Systematic Studies of Rheumatic Diseases studies. If responses in 4 of 6 selected measures were required for improvement (by greater than or equal to 20% for morning stiffness, Westergren erythrocyte sedimentation rate, joint pain/tenderness score, and joint swelling score, and by greater than or equal to 2 grades on a 5-grade scale, or from grade 2 to grade 1 for patient's and physician's overall assessments of current disease severity), few placebo-treated patients qualified as improved, whereas significantly more DMARD-treated patients demonstrated improvement. The proposed index appears to be useful in estimating the probability that an RA patient will improve if taking a placebo during a DMARD trial, and may be a useful tool for analysis of DMARD studies.

Anti-Inflammatory Agents↗
PubMed1990

Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression.

Suppression of rheumatoid factor (RF) production in rheumatoid arthritis (RA) has been variably attributed to the use of remittive agents per se or to clinical improvement associated with their use. There have been conflicting reports with regard to the influence of methotrexate (MTX) on serum RF levels in RA. We determined IgM-RF and IgA-RF levels in paired serum samples (obtained at study entry and completion) from RA patients enrolled in multicenter trials with the Cooperative Systematic Studies of Rheumatic Diseases program. After exclusion of the 14 IgM-RF-negative sera, there were samples from 30 MTX-treated patients and 52 placebo-treated patients. Changes in IgM-RF and IgA-RF levels were weakly associated with each other. Significant decreases in IgM-RF levels were observed in the MTX-treated patients, but not in the placebo group. These changes were most significant in the MTX-treated patients who improved clinically. There were significant decreases in IgA-RF levels at study completion among MTX-treated patients who had improved clinically and those who had not improved clinically, but not in the placebo group. The contributions of clinical improvement and MTX treatment to changes in serum IgM-RF and IgA-RF levels were examined using a logistic regression model. Changes in IgM-RF were strongly related to MTX treatment and, to a lesser extent, to clinical improvement; changes in IgA-RF were related only to MTX treatment. These results indicate that MTX treatment per se decreases both IgM-RF and IgA-RF levels, whereas clinical improvement correlates with decreased IgM-RF levels only.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1990

Effects of indomethacin, cyclosporin, cyclophosphamide, and placebo on collagen-induced arthritis of mice.

The long term effects of indomethacin, cyclosporin, cyclophosphamide, and placebo on collagen-induced arthritis in mice were tested under two different treatment protocols. A prophylactic experiment examined the effects of the daily drug administration for 180 days beginning one day before the first collagen injection. Under this dosage schedule, cyclophosphamide and cyclosporin decreased the severity of arthritis, while indomethacin did not. A therapeutic protocol examined the effects of these same drugs when daily administration was delayed until the animals had active disease at 78 days after the first collagen injection. Under this protocol, all three drugs reduced the progression of disease. In both protocols, the most significant suppression of arthritis was seen in animals receiving cyclophosphamide which was associated with a decrease in anti-collagen antibody levels. Collagen-induced arthritis in mice should be further investigated as a model to study the long term effects of "slow-acting" anti-rheumatic drugs.

Animals↗
PubMed1990

Helplessness and depression in rheumatoid arthritis.

Depression is common in rheumatoid arthritis (RA) populations and has been hypothesized to result from patients' belief that they cannot control their disease or its impact. In a sample of 106 patients with RA, we found that scores on a measure of helplessness mediated the relationship between severe, disabling RA and depression. Further, this association was independent of the previously demonstrated correlation between cognitive distortion and depression in RA patients. Thus, both helplessness and cognitive distortion may be important factors in the development and treatment of depression among RA patients.

Adaptation, Psychological↗
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

Clinical and laboratory outcomes during the treatment of rheumatoid arthritis with methotrexate.

Ten clinical and three laboratory outcomes were evaluated in 86 patients completing a double-blind placebo-controlled trial of methotrexate in rheumatoid arthritis. The improvement in all measured outcomes was statistically significantly better in patients receiving methotrexate than in patients receiving placebo. The correlations of the changes in outcome measures were calculated to determine if improvement in one parameter was associated with improvement in other clinical parameters. Associations between different clinical outcomes were often statistically significant. Associations between laboratory outcomes were also often statistically significant. However, the association between clinical outcomes and laboratory outcomes was generally poor.

Arthritis, Rheumatoid↗
PubMed1990

Challenging the pyramid. A new look at therapeutic approaches for rheumatoid arthritis. Earlier intervention with second line therapies.

It is clear that nonsteroidal antiinflammatory drugs (NSAID) may help control the pain and swelling of rheumatoid arthritis (RA) but do not retard joint destruction. Similarly, prednisone is effective in controlling pain and swelling but it cannot be established that it prevents or delays joint damage. When added to NSAID and prednisone, second line drugs (DMARD) have the potential to provide additional control of synovitis and improve function. Each second line drug has a unique tolerability and safety profile. Patients who are more likely to have a progressive course should be evaluated for second line drugs rather than risk irreversible damage.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: a post hoc analysis of three controlled trials.

This study assessed the relative efficacy and toxicity of second-line antirheumatic drugs in patients 65 years of age or older compared to younger counterparts. The results of three prospective, double-blind, parallel, randomized, multicenter trials were reanalyzed, stratifying outcomes by intervention and patient age. Efficacy was assessed by categorizing patient responses as follows: important improvement, no meaningful change, or progressive disease. Toxicity was analyzed by comparing withdrawal rates due to adverse effects. The three trials compared the following treatments: (1) D-penicillamine 10-12 mg/day versus azathioprine 1.25-1.5 mg/kg/day; (2) gold sodium thiomalate 50 mg intramuscularly weekly versus auranofin 6 mg/day versus placebo; and (3) pulse oral methotrexate 7.5-15.0 mg weekly versus placebo. At baseline, 103 patients age 65 or older were similar to 485 patients less than 65 years of age, with the exception of disease duration in all studies and erythrocyte sedimentation rate in one study. For patients completing each study, efficacy outcomes based on age were not significantly different. Withdrawal rates due to adverse drug reactions were also not significantly different.

Administration, Oral↗
PubMed1990

In vivo administration of interferon-gamma to patients with rheumatoid arthritis decreases numbers of circulating B cells.

We evaluated the expression of leukocyte cell surface antigens in patients with rheumatoid arthritis (RA) and healthy individuals using monoclonal antibodies and flow cytometry. Both 1 and 2-color analyses were performed. Markers evaluated included markers of T and B cell subsets, activation antigens, and antigens expressed on additional cell types. No major differences were seen between healthy persons and patients. The effects of in vivo administration of interferon-gamma (IFN-gamma) were studied in a clinical trial of the efficacy of this agent in the treatment of RA. Numbers of circulating B cells fell with administration of IFN-gamma. Expression of HLA-DR antigens on monocytes may have increased slightly with IFN therapy. There was no correlation between clinical response to IFN-gamma and change in any immune variables. Because of the observed alterations in B cell numbers, serum immunoglobulins were measured by radial immunodiffusion. There was no alteration of levels of most immunoglobulin isotypes as a result of therapy. There was a modest increase in serum IgA. There was no change in either rheumatoid factor or antinuclear antibody titers during IFN-gamma therapy.

Antibodies, Monoclonal↗
PubMed1989

Disability and depression in rheumatoid arthritis. A multi-trait, multi-method investigation.

In a sample of 107 patients with classic or definite rheumatoid arthritis (RA), we examined the convergent and divergent validity of measures of disability and depression. Scores on the self-report Disability index of the Health Assessment Questionnaire were highly correlated with physical therapist and spouse ratings of disability. Although Health Assessment Questionnaire disability scores were significantly correlated with self-reported and interviewer-assessed ratings of depression, these correlations were significantly smaller. Factor analyses of the Beck Depression Inventory (BDI) and rheumatologist ratings of BDI items indicated that this measure is highly contaminated by the inclusion of items reflecting RA disease severity. A dysphoric mood subcomponent of the BDI may be a more valid measure of depression in RA populations. Although depression and disability are clearly positively correlated in RA patients, depression scales that include somatic items are likely to yield an overestimate of the association. Finally, self-reported pain intensity was more clearly related to disability and reported recent disease activity than to depression.

Adult↗