Living with Behçet's disease. An insight into the impact of the illness on people's lives.
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Adaptation, Psychological↗
Biomedical subjects
A Silman
Publications and source records attributed to A Silman.
Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis.
The aim of the study was to investigate whether polymorphisms of macrophage migration inhibitory factor (MIF) determine susceptibility to or severity of inflammatory polyarthritis (IP). Genotypes for a single-nucleotide polymorphism (MIF-173*G/C) and a tetranucleotide (CATT)(n) repeat mapping to the promoter region of the MIF gene were compared between UK Caucasian IP cases (n=438) and controls (n=343). Both polymorphisms were also investigated for association with features of disease activity and severity at baseline and by 5 years. The MIF-173*C allele (OR 1.7, 95% CI 1.3-2.4, P=1.8 x 10(-4)) and the CATT(7) allele (OR 1.5, 95% CI 1.0-2.1, P=0.02) were found to be associated with increased susceptibility to IP. Furthermore, presence of the haplotype containing both associated polymorphisms was associated with a three-fold increase risk of developing IP. No association with disease severity or activity either at baseline or by 5 years was detected for either of the promoter polymorphisms studied. In conclusion, MIF is a susceptibility gene for the development of IP. The same alleles previously reported to be associated with susceptibility to juvenile idiopathic arthritis account for the increased risk. The promoter polymorphisms of MIF, investigated in this study, do not influence the severity of disease outcome by 5 years.
Adult↗
Contribution of patient related differences to multidrug resistance in rheumatoid arthritis.
BACKGROUND: There is a wide variation in responses to standard disease modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Whether multidrug resistance, failure to respond to several DMARDs, is a specific entity over and above that expected by chance alone is unclear. OBJECTIVE: To identify patients with RA who demonstrate a multidrug resistant phenotype and to determine what proportion of the variance in drug responses is due to patient related factors. METHODS: Patients with RA (1987 American College of Rheumatology criteria) were identified from clinics at Manchester Royal Infirmary and through the Arthritis Research Campaign National RA Repository. The clinic records were reviewed and multidrug resistance was defined as stopping three or more DMARDs owing to lack of efficacy after an adequate trial of the drug. Logistic regression measured by a random effects model was used to determine the relative contribution of the drug and subject related differences to the multidrug resistance. RESULTS: 265 patients (210 (79.3%) female) were studied. The mean (SD) age and disease duration were 52.2 (12.9) and 10.7 (8.8) years, respectively. Patients had a median (range) of 2 (1-8) DMARD courses. Failure of at least one DMARD due to inefficacy occurred in 105 (40%) and 13 (5%) were multidrug resistant. Overall, 35% of the variance in drug responses was due to between-subject differences (p=0.02). Rheumatoid factor (RF) status contributed significantly to this (OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained only 3% of the total variance in drug inefficacy. CONCLUSION: Multidrug resistance occurs in an uncommon (5%) but important subgroup of patients with RA. The between-subject variance is not fully explained by demographics and RF status. Understanding the biological mechanisms that contribute to multidrug resistance may suggest new therapeutic approaches and targets in RA.
Adult↗
Syndrome of symptomatic adult acetabular dysplasia (SAAD syndrome).
OBJECTIVES: To determine the prevalence of acetabular dysplasia in subjects presenting with hip pain to primary care and its relationship with radiographic osteoarthritis (OA) of the hip. DESIGN: Cross sectional analysis of a prospective cohort. SETTING: 35 general practices across the UK. SUBJECTS: 195 patients (63 male, 132 female) aged 40 years and over presenting with a new episode of hip pain RESULTS: The prevalence of acetabular dysplasia in this study of new presenters with hip pain was high (32%). There was no significant relationship between acetabular dysplasia and radiographic OA overall. CONCLUSIONS: The high prevalence of acetabular dysplasia across all grades of OA severity suggests that dysplasia itself may be an important cause of hip pain ("symptomatic adult acetabular dysplasia").
Adult↗
British Society for Rheumatology Biologics Register.
The British Society for Rheumatology (BSR) established a register of patients newly treated with biological agents, the BSR Biologics Register (BSRBR), which became active in January 2002. The goal is to register all patients in the United Kingdom with rheumatic diseases, newly starting treatment with these agents and to follow them up to determine the incidence of any short and long term hazards to health. The Register is also recruiting a comparison cohort of patients with rheumatoid arthritis treated with standard disease modifying antirheumatic drugs to determine the relative contributions of disease factors and other treatments apart from biological agents on any risks observed.
Antirheumatic Agents↗
A new approach to the development of assessment guidelines for osteoporosis.
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Absorptiometry, Photon↗
The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century.
BACKGROUND: It is 40 yr since the last age- and sex-specific estimates of the prevalence of rheumatoid arthritis (RA) for the UK were published. Since then the classification criteria for RA have been revised and there has been evidence of a fall in the incidence of RA, especially in women. OBJECTIVES: To estimate the age- and sex-specific point prevalence of RA (defined as fulfilment of a modification of the 1987 ACR classification criteria for RA on the day of assessment). The estimate was made in the primary care setting in Norfolk, UK. METHODS: A stratified random sample was drawn from seven age and gender bands. The 7050 individuals selected were mailed a screening questionnaire. Positive responders were invited to attend for a clinical examination. The sample was matched against the names in the Norfolk Arthritis Register (NOAR), a register of incident cases of inflammatory polyarthritis which has been in existence since 1990. RESULTS: The overall response rate was 82%. Sixty-six cases of RA were identified. Extrapolated to the population of the UK, the overall minimum prevalence of RA is 1.16% in women and 0.44% in men. A number of incident cases of RA previously notified to NOAR were not identified as cases in the survey because they had entered into treatment-induced remission. In addition, some cases who failed to attend for examination had significant disability. These prevalence figures are therefore an underestimate. CONCLUSIONS: The prevalence of RA in women, but not in men, in the UK may have fallen since the 1950s.
Adolescent↗
High resolution linkage and association mapping identifies a novel rheumatoid arthritis susceptibility locus homologous to one linked to two rat models of inflammatory arthritis.
Rheumatoid arthritis (RA) is an oligogenic autoimmune disease but, to date, linkage and association to major histocompatibility complex (MHC) has been the only consistent finding in genetic studies. However, MHC is estimated to contribute only 30-40% of the total genetic component to disease susceptibility. Studies in animal models of inflammatory arthritis have identified a number of putative vulnerability loci but the homologous regions in the human genome have not previously been investigated as candidate RA susceptibility loci. We have investigated linkage to five regions homologous to those identified in animal models of inflammatory arthritis in RA affected sibling pair (ASP) families. Linkage to 17q22 syntenic to a susceptibility locus common to two experimental rat models was detected in 200 RA ASP families and replicated in a further 100 RA ASP families. Linkage to additional markers mapping to the area has refined the extent of linkage to a 4 cM region. Association to one of the markers (D17S807) was demonstrated in this cohort using extensions of the transmission disequilibrium test. Association to two 2-marker haplotypes including this marker was detected in an independent cohort of single-case RA families, thus narrowing the region harbouring the aetiological mutation to approximately 1 cM. This is the first time that an arthritis susceptibility locus mapped in experimental animal models of disease has been used to identify a novel RA susceptibility locus in humans. The difficult task of identifying a disease mutation from a linkage result should, in this case at least, be facilitated by the combined use of animal and human based investigations.
Animals↗
Association between rheumatoid arthritis and polymorphism of tumor necrosis factor receptor II, but not tumor necrosis factor receptor I, in Caucasians.
OBJECTIVE: Tumor necrosis factor (TNF) is a powerful mediator of inflammation in rheumatoid arthritis (RA). In vivo, its acute effects are limited by binding to soluble receptors (TNFR), suggesting that TNFR genes could be important candidate risk factors. The present study was undertaken to investigate association of polymorphisms of TNFRI and TNFRII with RA in subjects in the UK. METHODS: Unrelated Caucasian RA patients (n = 291) and healthy Caucasian controls (n = 143) were genotyped for A/G polymorphism in exon 1 of TNFRI. From this sample, 240 of the patients and 137 controls were also typed for a single-nucleotide polymorphism (SNP) in exon 6 of the TNFRII gene. In followup studies, DNA samples from UK Caucasian RA patients with a positive family history (n = 149) and UK Caucasian patients with sporadic RA (n = 208) were also typed for the exon 6 TNFRII polymorphism. RESULTS: TNFRI polymorphism was not associated with RA (odds ratio [OR] for GG genotype 0.93, 95% confidence interval [95% CI] 0.54-1.60). For TNFRII, in the initial study group, patients with RA were significantly more likely to be positive for both the G allele and GG genotype than were controls (OR for GG genotype 2.55, 95% CI 1.11-5.86). The association appeared to be confined to those with a family history of RA. This finding was replicated in an independent cohort of patients with familial RA. CONCLUSION: The results of this study provide evidence of association between an SNP in the TNFRII gene and RA, the strongest association being observed in patients with a family history. No evidence of association between RA and TNFRI was demonstrated.
Arthritis, Rheumatoid↗
Predicting radiographic hip osteoarthritis from range of movement.
OBJECTIVES: The primary objective was to test the hypothesis that new attenders in primary care with hip pain and radiographic osteoarthritis (OA) have a decreased range of movement compared with those without OA. The secondary objective was to define the planes of movement and thresholds that were the most discriminatory for OA. METHODS: Men and women aged 40 yr and over presenting with a new episode of hip pain were recruited from 36 general practices across the UK. A standardized radiographic and clinical examination was performed. The discriminating ability of the range of movement for each plane to identify those with radiographic OA was assessed using receiver operating characteristic curves. RESULTS: New hip pain attenders with radiographic OA had restricted movement at the hip compared with those without radiographic change. Restriction in internal rotation was the most predictive and flexion the least predictive of radiographic OA. At this cut-off, restriction in any single plane had a sensitivity of 86% for moderate and 100% for severe OA (specificity was 54 and 42% respectively). Restriction in all three planes had greater discrimination (sensitivity was 33% for mild to moderate OA and 54% for severe OA; specificity was 93 and 88% respectively). CONCLUSIONS: Restriction in range of movement was predictive of the presence of OA in these new presenters to primary care with hip pain, and the results of this examination could be used to inform decisions regarding radiography.
Adult↗
Health and exposures of United Kingdom Gulf war veterans. Part I: The pattern and extent of ill health.
OBJECTIVES: To assess the health of United Kingdom Gulf war veterans, to compare their health to that of similar personnel not deployed, to describe patterns of ill health in both groups, and to estimate their extent. METHODS: Main Gulf (n=4795) and validation Gulf (n=4793) cohorts were randomly selected within strata from the population deployed to the Gulf and a non-Gulf cohort (n=4790) from those who were not sent. Seven years after the war subjects completed a questionnaire about their health in the past month, including 95 symptom questions and two manikins on which to shade areas of pain or numbness and tingling. Responses were subjected to a principal component analysis with rotation and to a cluster analysis within each cohort. Mean symptom score was used as a measure of severity. Areas shaded on the manikins were coded to indicate widespread pain and possible toxic neuropathy. RESULTS: A response of 85.5% was achieved. Those who had been to the Gulf were more troubled by every symptom with a mean severity score (3.0) substantially greater than in the non-Gulf cohort (1.7). Seven factors were extracted accounting for 48% of the variance. The scores on five factors (labelled psychological, peripheral, respiratory, gastrointestinal, and concentration) were significantly worse in those who had been to the Gulf. Symptoms suggestive of peripheral neuropathy were found more often (12.5%) in the Gulf than the non-Gulf (6.8%) cohorts. Widespread pain was also found more often (12.2% Gulf; 6.5% non-Gulf). Those who had been to the Gulf were found disproportionately (23.8%) in three clusters with high mean severity scores; only 9.8% of non-Gulf respondents were in these clusters. There was no evidence of an important excess in the use of alcohol, tobacco, or referral to hospital specialists by those who had been to the Gulf. For the same level of reported ill health those who had been to the Gulf were less likely to be referred to specialists than non-Gulf veterans. CONCLUSION: 7 Years after the war, the Gulf war veterans were more troubled about their health than those who had not been sent, with a substantial subgroup reporting a pattern of symptoms suggestive of a significant decline in health.
Adult↗
Health and exposures of United Kingdom Gulf war veterans. Part II: The relation of health to exposure.
OBJECTIVES: To investigate whether, in personnel who served with the United Kingdom forces in the Gulf war, self reported exposures were related to symptoms in a way that was consistent, specific, and credible. METHODS: Responses to symptom and exposure questionnaires, completed 7 or more years after the war, were collected from 7971 subjects deployed in the Gulf, from two exposed cohorts, in a study with an overall response rate of 85.5%. Exposures were considered in three groups, those outside the control of the subjects, the use of prophylaxis, and indicators of susceptibility. Health indices derived from symptom questionnaires were related to reports of 14 exposures in these three groups in a series of multiple regression analyses to allow for confounding. The relation of exposure to complaints of widespread pain and to symptoms suggesting peripheral neuropathy were examined by logistic regression. RESULTS: Consistent but weak correlations between exposures and with health effects were found in independent analyses of the two (main and validation) cohorts. Three exposures outside the control of the subject, the number of inoculations, the number of days handling pesticides, and the days exposed to smoke from oil fires, were consistently and independently related to severity. The number of inoculations was also associated with higher scores on a factor weighted on symptoms associated with skin and musculoskeletal complaints. The number of days handling pesticides related particularly to scores on a neurological factor and to symptoms consistent with toxic neuropathy. CONCLUSION: The relations between exposures and ill health were generally weak. Consistent, specific, and credible relations, warranting further investigation, were found between health indices and two exposures, the reported number of inoculations and days handling pesticides.
Adult↗
Lack of relationship between functional ability and skin score in patients with systemic sclerosis.
OBJECTIVE: To examine the hypothesis that functional ability is related to skin score in patients with systemic sclerosis (SSc). METHODS: In 140 patients with SSc attending clinics in the northwestern region of England, functional ability (measured using a recently developed 11 item functional questionnaire) was correlated with skin score (measured using a modified Rodnan technique--17 sites, maximum score 3 for each site). RESULTS: The median functional score was 6 (range 0-31) and the median skin score 7 (range 0-37). There was no correlation between functional score and total skin score (rS = 0.11, p = 0.19, Spearman). Because most of the questions of the functional score related to upper limb function, separate analyses were undertaken restricting consideration of skin involvement to (1) upper limbs only and (2) digital skin only, versus the overall functional score. Again, no evidence of an association was observed. CONCLUSION: Functional ability in this broad group of patients with SSc cannot be predicted from the skin score. Although skin score is useful prognostically, it is not a major determinant of a patient's ability to perform activities of everyday living.
Adult↗
Linkage and association analysis of candidate genes in rheumatoid arthritis.
OBJECTIVES: To test for linkage and association to rheumatoid arthritis (RA) in multiplex families for polymorphic markers in candidate gene loci. Loci including the cytokine cluster on 5q31.1 and IL10, both previously investigated in RA, were included along with several other genes including ICAM-1, cMYC, the cytokine cluster on 17q11.2 and IL1RA. METHODS: One hundred eighty-five multiplex RA families were genotyped for 11 microsatellite markers close to candidate genes. Markers showing evidence of linkage and/or association to RA were tested in a further cohort of families (n = 99). RESULTS: A single microsatellite marker in the GSTM4 gene showed some evidence of linkage, LOD 1.6 (p = 0.006). However, there was no evidence of excess allele sharing in the second cohort of families tested. There was also evidence of association to RA, using the transmission disequilibrium test for a dinucleotide repeat in the IRF gene in the cytokine cluster on 5q31.1; this was not replicated in a second cohort of families. CONCLUSION: Our results do not provide evidence of a role for these genes in RA susceptibility.
Arthritis, Rheumatoid↗
Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis.
OBJECTIVES: To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing prostaglandin analogues versus placebo were eligible if they reported clinical outcomes within the start of therapy, and if the dropout rate was less than 35%. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous, respectively. MAIN RESULTS: Seven randomized trials and 332 patients were included. Five of the seven trials were of parallel design. Five trials compared I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost. Some trials were dose finding trials so various doses of Iloprost were used. Due to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost appears to be effective in the treatment of secondary Raynaud's phenomenon. REVIEWER'S CONCLUSIONS: Intravenous Iloprost is effective in the treatment of Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and severity of attacks and preventing or healing digital ulcers. The effect seems to be prolonged after the intravenous infusion is given. Oral Iloprost may have less efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy when given orally for the treatment of Raynaud's phenomenon secondary to scleroderma.
Humans↗
Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis.
OBJECTIVES: To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systematic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing ketanserin versus placebo were eligible if they reported clinical outcomes of interest. Trials with dropout rates greater than 35% were excluded. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous outcomes, and a weighted mean difference (WMD) was carried out on all continuous outcomes. A fixed effects or random effects model were used if the data was homogeneous or heterogeneous, respectively. MAIN RESULTS: Three trials and 66 patients were included. The proportion improved was significantly better in the group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37). However, when comparing ketanserin to placebo, the decrease in severity of RP attacks favoured placebo but this was not statistically significant. Side effects were significantly more common in the group using active treatment with an OR of 5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration of attacks decreased significantly in the ketanserin group. REVIEWER'S CONCLUSIONS: Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.
Humans↗
Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis.
OBJECTIVES: To assess the effects and toxicity of Cyclofenil versus placebo for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or Vasospasm, Scleroderma or Progressive Systematic Sclerosis or Connective Tissue Disease or Autoimmune Disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized trials comparing cyclofenil versus placebo were eligible if they reported any clinical outcomes within the trial. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratio (OR) was calculated for all dichotomous outcomes, and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous respectively. MAIN RESULTS: One trial with 38 patients was included. There was a trend for Cyclofenil to demonstrate more improvement and more dropouts compared to placebo, but there were no statistically significant differences. REVIEWER'S CONCLUSIONS: Cyclofenil is not effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Cyclofenil↗
Prazosin for Raynaud's phenomenon in progressive systemic sclerosis.
OBJECTIVES: To determine the effects and toxicity of prazosin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to December 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: Randomized controlled trials comparing prazosin versus placebo were eligible if they reported clinical outcomes from the start of therapy. Trials with a greater than 35% dropout were excluded. Trials were included if patients with diffuse or limited scleroderma were the subjects. If patients with other connective tissue diseases or primary Raynaud's were included, the trial was used if the data on the scleroderma patients could be extracted from the paper. DATA COLLECTION AND ANALYSIS: All data were abstracted by two independent and trained reviewers (DF, AT), and verified by a third reviewer (JP). Each trial was assessed independently by the same two reviewers for its quality using a validated quality assessment tool (Jadad 1996). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was carried out on all continuous outcomes. Fixed effects and random effects model were used if the data was homogeneous or heterogeneous, respectively. MAIN RESULTS: Two trials with a total of 40 patients were included. Prazosin has been found in two randomized controlled cross-over trials to be more effective than placebo in the treatment of Raynaud's secondary to scleroderma. However, the positive response is modest and side effects are not rare in those taking prazosin. REVIEWER'S CONCLUSIONS: Prazosin is modestly effective in the treatment of Raynaud's phenomenon secondary to scleroderma.
Adrenergic alpha-Antagonists↗