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Biomedical subjects

P G Conaghan

Publications and source records attributed to P G Conaghan.

At least 37 records · Page 2Linked to original sources
PubMed2003

FcgammaRIIIA-158V and rheumatoid arthritis: a confirmation study.

OBJECTIVES: To develop a robust assay for genotyping the FcgammaRIIIA-158V/F polymorphism and to confirm the putative association between the FcgammaRIIIA-158V allele and rheumatoid arthritis (RA). METHODS: This allelic association study examined the FcgammaRIIIA-158V/F polymorphism for association with RA. A novel single-stranded conformational polymorphism assay was used to genotype 828 RA patients and 581 controls from the UK. RESULTS: The FcgammaRIIIA-158V allele was associated with both RA (P=0.02) and nodules (P=0.04). Individuals homozygous for this higher affinity allele had a significantly increased risk of RA (OR 1.53, 95% CI 1.08-2.18) and the development of nodules (OR 2.20, 95% CI 1.20-4.01). There was no evidence of an interaction with the shared epitope. CONCLUSIONS: We have developed a novel assay to genotype the FcgammaRIIIA-158F/V polymorphism and confirmed that homozygosity for the FcgammaRIIIA-158V allele is associated with UK Caucasian RA, particularly in those individuals with nodules, suggesting FcgammaRIIIA may play a role in determining disease severity or in the development of nodules per se.

Adolescent↗
PubMed2002

Update on osteoarthritis part 1: current concepts and the relation to exercise.

There appears to be an increased risk of lower limb osteoarthritis in participants of repetitive, high impact sports, and this is strongly associated with joint injury. There seems to be little risk associated with recreational running. Assessment of risk for osteoarthritis should take into account the nature of the sport, intensity of training, presence of previous injury, body mass index, and occupation.

Athletic Injuries↗
PubMed2001

Predictors of outcome in patients with oligoarthritis: results of a protocol of intraarticular corticosteroids to all clinically active joints.

OBJECTIVE: To determine the outcome and the factors that predict the persistence of synovitis following intraarticular corticosteroid injections in patients with recent-onset oligoarthritis. METHODS: Fifty-one patients with < or =5 joints with synovitis (disease duration < or =12 months) were treated with intraarticular injections of methylprednisolone into all joints with clinical synovitis. Predictors of outcome were sought, with the primary end point a complete response (no synovitis on clinical examination) at 12 weeks. RESULTS: Patient's and physician's assessments of disease activity, the swollen joint count, and function (by Health Assessment Questionnaire) were all significantly improved at 12 weeks (P < 0.001). Twenty-nine patients (57%) were judged to have had a complete response at 2 weeks. The best predictor of response at 12 and 26 weeks was the presence or absence of synovitis at 2 weeks (P = 0.002 and P = 0.004, respectively). At 52 weeks of followup, nearly 50% of the patients still had evidence of synovitis. CONCLUSION: Intraarticular corticosteroids are an effective treatment for early oligoarthritis, but there is still a high level of long-term morbidity. Failure to respond by 2 weeks indicates a high likelihood of persistent disease, and this is relevant when producing management guidelines and selecting patients for studies focusing on early intervention.

Adult↗
PubMed2001

Imaging the joints in early rheumatoid arthritis.

Radiography is the most widely utilized imaging modality for early rheumatoid arthritis, determination of radiographic progression remaining a crucial part of the evaluation of therapy. Conventional radiography is, however, insensitive for showing bone damage in early disease and is totally unsuitable for assessing synovial inflammation. The recognition of these limitations has led to intense interest in the multiplanar imaging capabilities of magnetic resonance imaging in rheumatoid arthritis and to an increasing use of ultrasonography for assessing synovitis and bone damage. This chapter discusses the role of radiography in early rheumatoid arthritis and the emerging use and role of magnetic resonance imaging and ultrasonography in evaluating synovitis and bone damage. The relationship between synovitis and bone damage is also addressed in the light of recent magnetic resonance imaging observations.

Arthritis, Rheumatoid↗
PubMed2001

The therapeutic approach of early intervention for rheumatoid arthritis: what is the evidence?

OBJECTIVE: The concepts of early intervention and early arthritis clinics for the management of rheumatoid arthritis (RA) were introduced almost a decade ago. The evidence for these is diverse and the best therapeutic approach remains vehemently debated. This review addresses these issues. METHODS: The MEDLINE database was searched to identify relevant papers satisfying inclusion criteria for disease duration and no previous use of disease-modifying anti-rheumatic drugs (DMARDs). Where possible, evidence was obtained from randomized controlled trials. We selected the most relevant topics to best justify early therapeutic intervention in RA. RESULTS: The benefit of DMARDs over placebo and delayed therapy is unquestionable from the studies presented, with reduction in bone damage and preservation of function. Through prevention of disability, early treatment should be the most cost-effective approach. The evidence presented supports the use of DMARDs when the diagnosis of RA is first made. Delay in treatment may result in irreversible damage. There is insufficient evidence to recommend combination therapy for all patients at disease onset. Further research into newer therapies is required before their routine first-line use is recommended. CONCLUSIONS: Early therapeutic intervention in RA reduces long-term disability and joint damage. Optimal management appears to be the early identification of non-responders and targeted combination therapy. Biological therapies have the potential to revolutionize the treatment of early RA.

Adrenal Cortex Hormones↗
PubMed2000

Treatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone.

OBJECTIVE: To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ). METHODS: Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n = 40) or SSZ alone (n = 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks. RESULTS: After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (approximately 10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P = 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P = 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm. CONCLUSION: In poor-prognosis RA patients, "aggressive" combination therapy led to more rapid disease suppression but did not result in significantly better ACR response or remission rates. This suggests that in poor-prognosis disease, an approach based on identifying patients with poor treatment responses before extra therapy is added ("step-up" approach) may be more appropriate than the use of combination therapy in all patients from the outset.

Adrenal Cortex Hormones↗
PubMed2000

The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography.

OBJECTIVE: The ability to make an early, accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important with the availability of new, expensive, and targeted therapies. However, plain radiography, the traditional method of detecting the characteristic bone erosions and an important adjunct in establishing a diagnosis of RA, is known to be insensitive. This study compared sonography, a modern imaging technique, with conventional radiography for the detection of erosions in the metacarpophalangeal (MCP) joints of patients with RA. METHODS: One hundred RA patients (including 40 with early disease) underwent posteroanterior radiography and sonography of the MCP joints of the dominant hand. Twenty asymptomatic control subjects also underwent sonography. Erosion sites were recorded and subsequently compared using each modality. Magnetic resonance imaging (MRI) was performed on the second MCP joint in 25 patients with early RA to confirm the pathologic specificity of sonographic erosions. Intraobserver reliability of sonography readings was assessed using video recordings of 55 MCP joint scans of RA patients, and interobserver reliability was assessed by comparing 160 MCP joint scans performed sequentially by 2 independent observers. RESULTS: Sonography detected 127 definite erosions in 56 of 100 RA patients, compared with radiographic detection of 32 erosions (26 [81%] of which coincided with sonographic erosions) in 17 of 100 patients (P < 0.0001). In early disease, sonography detected 6.5-fold more erosions than did radiography, in 7.5-fold the number of patients. In late disease, these differences were 3.4-fold and 2.7-fold, respectively. On MRI, all sonographic erosions not visible on radiography (n = 12) corresponded by site to MRI abnormalities. The Cohen-kappa values for intra- and interobserver reliability of sonography were 0.75 and 0.76, respectively. CONCLUSION: Sonography is a reliable technique that detects more erosions than radiography, especially in early RA. Sonographic erosions not seen on radiography corresponded to MRI bone abnormalities. This technology has potential in the management of patients with early RA/inflammatory arthritis and is likely to have major implications for the future practice of rheumatology.

Adult↗
PubMed1999

The relationship between synovitis and bone changes in early untreated rheumatoid arthritis: a controlled magnetic resonance imaging study.

OBJECTIVE: The interrelationship between synovitis and bone damage in rheumatoid arthritis (RA) is a subject of controversy. Using magnetic resonance imaging (MRI), this study followed the bone changes in early RA and determined their relationship to synovitis. METHODS: Thirty-one patients with early RA who had swelling of the metacarpophalangeal (MCP) joints and 31 healthy control subjects with no clinical evidence of arthritis underwent MRI of the second through fifth MCP joints of the dominant hand by use of a 1.5T scanner. Coronal T1-weighted and T2-fat suppressed (FS) sequences were performed to evaluate bone edema, and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) pulse sequences were obtained to evaluate synovitis. Bony abnormalities were described as bone edema (low signal on T1-weighted sequences and intermediate/high signal on T2 FS sequences adjacent to the bone cortex) or as bone cysts (circular juxtacortical abnormalities with low signal on T1-weighted images and with very high signal on T2 FS sequences). Contrast and noncontrast MRI films were scored in a blinded manner, and Fisher's exact probability test was used to determine differences between groups. RESULTS: Twenty-one of the 31 RA patients (68%) had bone edema, which was seen in 43 of 124 joints (35% of joints) and 3 of the 31 control subjects had bone edema seen in 3 of 124 joints (2% of joints) (P < 0.0001). Thirty RA patients (97%) had Gd-DTPA-confirmed MCP joint synovitis, and bone edema was seen in 40 of the 75 joints with Gd-DTPA-proven synovitis (53%), but in only 3 of 49 without (6%) (P < 0.0001). CONCLUSION: MCP joint bone edema is present in the majority of patients with RA at presentation, but is seen only occasionally in normal control subjects. The fact that bone edema occurred rarely in the absence of synovitis in patients with RA suggests that bony changes in RA are secondary to synovitis.

Adult↗
PubMed1999

The relationship between pityriasis rubra pilaris and inflammatory arthritis: case report and response of the arthritis to anti-tumor necrosis factor immunotherapy.

Pityriasis rubra pilaris (PRP) refers to a group of erythematous, scaling dermatologic conditions that have been associated with seronegative arthritis. We report a case of polyarthritis in a young man with PRP in which magnetic resonance imaging suggested an entheseal-based pathology for the joint disease. The arthritis, but not the skin condition, demonstrated dramatic response to anti-tumor necrosis factor immunotherapy.

Adolescent↗
PubMed1999

Established rheumatoid arthritis.

Currently the diagnosis of rheumatoid arthritis (RA) may be difficult; the ACR criteria appear most sensitive and specific in long-standing disease. Without clear definition or diagnostic criteria for early disease it is difficult to define late or established RA. The distinction between early and established RA has been further blurred by recent imaging studies that suggest even in what is currently termed early disease, there is evidence of joint damage. The natural history of RA suggests that most patients with clinic-diagnosed RA have a progressively disabling course, but evidence is growing that modern therapeutic strategies result in better long-term outcomes, especially when applied early in the disease course. In established disease, quantitative markers such as C-reactive protein (CRP) give prognostic information, but in the pre-erosive, early phase of the disease the qualitative markers such as rheumatoid factor (RF) and shared epitope are crucial. As rheumatologists, our major aims must remain: (1) to diagnose the disease as early as possible; (2) to identify those patients with poor prognosis who will benefit most from targeted therapy; and (3) to aim for more intensive disease control irrespective of disease duration.

Arthritis, Rheumatoid↗
PubMed1998

Disease-modifying antirheumatic drugs.

Disease-modifying antirheumatic drug (DMARD) therapy is now clearly accepted as the primary treatment for rheumatoid arthritis, with an increasing emphasis on use of combination therapy. Data on combination therapy have highlighted the difficulties in performing these studies and the large number of patients required to produce meaningful results. Combination studies have focused on use of rapidly decreasing high-dose steroids as a part of the combination and emphasize the importance of using patients with early rheumatoid arthritis. Even with relatively aggressive use of DMARDs, the majority of patients develop erosions. Adverse reactions to DMARDs continue to concern clinicians, although evaluation of the frequency of these events has led to a reappraisal of previously accepted monitoring strategies in some cases. For example, it may not be cost-effective to subject patients on antimalarials to regular review by an ophthalmologist because of the low frequency of serious eye defects. Studies have also identified risk factors for the development of pulmonary toxicity in association with methotrexate. That DMARDs are effective in treating rheumatoid arthritis is beyond question-just how effective they are and what combinations of DMARDs will show improved efficacy will provide data for the next annual review.

Antimalarials↗
PubMed1998

Increased expression of human type IIa secretory phospholipase A2 antigen in arthritic synovium.

OBJECTIVE: To determine the localisation and level of expression of human type IIa secretory phospholipase A2 (sPLA2) in the synovium of rheumatoid arthritis (RA), osteoarthritis (OA), and non-arthritic (NA) patients and to examine the relation between sPLA2 and histological features of inflammation. METHODS: Immunoperoxidase staining using the anti-sPLA2 monoclonal antibody 9C1 was performed on frozen sections of knee synovium of 10 RA, 10 OA, and 10 NA patients. sPLA2 positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double labelling immunofluorescence confocal microscopy with antibodies to CD14 or CD45 and 9C1 was used to determine cell type specificity. Inflammation was assessed by semiquantitative scoring of lining layer thickness and mononuclear cell infiltrates (MC) and a cumulative inflammation score, generated by summing the two parameters. Scores in each group were compared using non-parametric statistical analysis. RESULTS: sPLA2 was localised to endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in all tissue sections. In RA and OA sections, staining was seen in both macrophage-like and fibroblast-like cells in the synovial lining layer (LL) and subsynovial lining layer (SLL). Perineural cells stained positively. Subintimal lymphoid aggregates (LA) were negative in all sections. The RA group showed significantly greater staining in extravascular synovial tissue (median 3.6, range 1.5-6.0) than the OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups (p < 0.05). LL staining was significantly higher in RA than both OA and NA sections (p < 0.05). The OA group showed a trend to higher staining scores than the NA group that did not reach significance. There was a significant correlation between the sPLA2 staining score and inflammation score within the RA patient group (p < 0.05). CONCLUSIONS: The synovium is a site of increased expression of sPLA2 antigen in both RA and OA relative to NA. Its presence in both fibroblast and macrophage-like cells in the LL and SLL of synovial tissue in RA and OA, but not NA, indicates that the enzyme is specifically induced in these regions in both conditions with expression in the LL being particularly characteristic of RA. The widespread expression of sPLA2 in synovium suggests it is likely to play a significant part in synovial pathology.

Adult↗
PubMed1997

Are rheumatoid arthritis patients more willing to accept non-steroidal anti-inflammatory drug treatment risks than osteoarthritis patients?

One hundred and thirty-four patients with either osteoarthritis or rheumatoid arthritis, and with a history of current or past non-steroidal anti-inflammatory drug (NSAID) treatment, were interviewed regarding the benefits, expectations and side-effects of NSAID therapy. Their willingness to accept risks in medical treatment was also evaluated. Both groups experienced positive effects of the NSAID treatment corresponding to their expectations. However, rheumatoid arthritis patients were significantly more willing to accept gastrointestinal side-effects when given an effective NSAID than the osteoarthritis patients, and they were also more willing to take risks in trying a hypothetical new NSAID that had been shown to be effective in clinical trials.

Adult↗
PubMed1997

Anti-rheumatic drug-prescribing behaviour of Australasian rheumatologists 1984-1994.

The prescribing behaviour of Australian and New Zealand rheumatologists was studied in 1994 using a questionnaire, and the results compared with a similar questionnaire administered in 1984. Perceived differences in efficacy and toxicity for disease-modifying anti-rheumatic drugs (DMARDs) and cytotoxics were reported. Over the decade, methotrexate and sulphasalazine have become the most commonly used anti-rheumatic agents, and methotrexate is clearly seen as the most effective drug. Wide variations in monitoring practices for DMARDs were reported, highlighting the need for cost-effectiveness studies on monitoring. There was low usage of functional outcome measurements in assessing patients.

Australia↗
PubMed1997

Disease-modifying antirheumatic drugs.

The case for early intervention with disease-modifying antirheumatic drugs is strengthened by published reports during the past year. These drugs include methotrexate, gold sulfasalazine, and antimalarial agents. The American College of Rheumatology issued guidelines for the management of rheumatoid arthritis and for monitoring the toxicity of antirheumatic drugs. Studies on the mechanisms of action of disease-modifying antirheumatic drugs focused on their effects on cytokines and their receptors. The toxic effects of disease-modifying antirheumatic drugs remained an important issue, especially the adverse pulmonary effects of methotrexate. An important trial demonstrated a beneficial effect of triple disease-modifying antirheumatic drug therapy (methotrexate, sulfasalazine, and hydroxychloroquine) over individual agents.

Antimalarials↗