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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12858438 Increased risk of tuberculosis in patients with rheumatoid arthritis. 2003 Jul OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.
11886963 The presence of the HLA-DRB1 shared epitope correlates with erosive disease in Chilean pat 2002 Feb OBJECTIVE: To assess the contribution of the HLA-DRB1 shared epitope (SE) to the radiological outcome of rheumatoid arthritis (RA) after 6 yr of follow-up in a reported series of 129 Chilean patients with established disease. METHODS: A prospective study was conducted between 1992 and 1998 using hand radiographs to assess disease outcome in a published series of patients in whom two doses of the SE were present in 20%, one dose was present in 34% and the SE was absent in 46%. At study entry, 29 of the 92 patients with hand radiographs were at Steinbrocker stages I or II (non-erosive), with a median disease duration of 2.8 yr (0.4-17). RESULTS: In 1998, 113 (87%) of the patients were alive. One hundred and eight patients underwent complete clinical evaluation. Their median age was 57 yr (range 30-81) and the median disease duration was 15 yr (6-50). We were able to study 25 of the 29 patients who had non-erosive disease at study entry in 1992. We found that 10 of 11 patients having one or two doses of the SE developed erosive disease compared with three of 14 without the SE (Yates' corrected P=0.0023, relative risk 4.24, 95% confidence interval 1.53-11.77). CONCLUSIONS: These observations support and extend the notion that the presence of the SE in one or two doses can predict the development of erosions even in RA populations in whom the SE is not as prevalent as in Caucasians.
15291772 Development of web-based qualitative and quantitative data collection systems: study on da 2004 Sep With the sharp rise in Internet access in recent years, the Internet is increasingly being used for research. We have developed two new systems using the Internet for both quantitative and qualitative data collection. One is a dynamic system for creating questionnaires and collecting responses and the other is an individual patient support follow-up system. These systems do not depend on the capacity of computers or servers and enable researchers to interact with participants privately and asynchronously. We have used these systems to collect data on daily symptoms and journal entries from 12 community-dwelling women with rheumatoid arthritis (RA) for a minimum of 1 month. The mean number of data submissions per month was 14.2 +/- 7.8, with the majority recording entries every day, and some submitting several times a day. The combination of two types of data elucidated the changes in coping and coping strategies in conjunction with changes in symptoms, even in a single day, and the coexistence of positive and negative coping. Research participants benefited from web-based symptom management and counseling resulting from 1 month of frequent interactions with the researcher. The use of the Internet for nursing research and interventions thus seems to show promising results.
11880907 Successful hip arthroplasty using cementless titanium implants in rheumatoid arthritis. 2002 Mar Over a period of eight years, we implanted a total of 76 cementless hip prostheses in patients with rheumatoid arthritis. The clinical results of 47 patients (70 hips) increased from a mean Harris Hip Score of 33 to 85 after an average of 49 months (range 1-11 years). One threaded cup has had to be revised because of loosening, and one stem because of femoral fracture. At the latest follow-up, 88% of Hofer-Imhof threaded cups had complete bone ingrowth (Type 0); 10% had near-complete bone ingrowth with minimal radiolucency in one third of the bone contact area (Type 1), and 2% had radiolucency in two thirds of the bone contact area (Type 2). Hemispherical push-in cups showed significantly more radiolucency around the cup. For the stems (Uni, Zweymüller SL), 83% showed no radiolucency (Type 0); 17% had radiolucency only very proximally (Type 1). Minor remodelling (Type 1) occurred in 60% of the femoral shafts; 30% had moderate femoral density loss (Type 2), and 10% had severe bone loss and cortical thinning (Type 3). There was no correlation between marked shaft atrophy and clinical symptoms. With regard to radiolucency and remodelling, there was no significant difference between the two types of stem used. Cementless hip arthroplasty using titanium implants has an excellent outcome in the medium term.
12215862 Activated factor XII in rheumatoid arthritis. 2002 Sep Rheumatoid arthritis (RA) is associated with premature mortality, with approximately 50% of deaths being due to cardiovascular disease. It has been shown that the increased incidence of cardiovascular disease is independent of traditional risk factors. Previous studies have shown an increased risk of coronary heart disease with increased levels of activated factor XII (FXIIa). The aim of this study was to investigate levels of FXIIa in patients with RA. We studied 32 patients with RA and 30 age- and sex-matched control subjects. We found FXIIa levels significantly increased in the patient group, with 56% of the patients and 6.7% of controls having levels greater than or equal to 2 ng/ml. A previous study has shown that individuals with levels of 2 ng/ml or more have an increased risk of coronary heart disease. Measurement of FXIIa could perhaps help to identify an 'at risk' group of patients, allowing early intervention therapy.
12231027 Family functioning in the context of chronic illness in women: a Korean study. 2002 Sep The aims of this study were to clarify the concept of family functioning in the context of a female family member's chronic illness, and to describe the processes by which the housewife copes with the situation. The study applied the hybrid model of concept development, which consists of three phases: theoretical, empirical, and analytic. In the theoretical phase, a working definition of family functioning was established and the dimensions of family functioning and subconcepts were identified through an extensive review of the literature. In the empirical phase, in-depth interviews with members of six normal families and seven families in which the housewife had a long-term diagnosis of rheumatoid arthritis were carried out in order to gain descriptions of family functioning in both contexts, and to assess how the housewife coped with her illness in relation to family functioning. The final analytic phase identified the differences and similarities in family functioning between the normal family and family with a chronically ill housewife. A refined definition of family functioning emerged that identified the concept in terms of a complex set of functional dimensions comprising affective, structural, control, cognitive, and external relationships. The data revealed that family functioning is dynamically changed when the housewife becomes ill with a chronic disease. Three types of adaptation process were identified by which the housewives adapted to family functioning in the context of their chronic illnesses: negotiated, self-accommodating, and separated-enduring. The implications of these findings for research and nursing practice are discussed.
12510360 [Clinical implication of cyclosporin for rheumatoid arthritis]. 2002 Dec Cyclosporin is a non-cytotoxic immunomodulating drug which inhibits NF-AT-dependent IL-2 transcription in lymphocytes. Cyclosporin is, therefore, beneficial as a monotherapy or as a combined therapy with methotrexate for refractory rheumatoid arthritis (RA). We also document that cyclosporin recovers the low concentration of intracellular multidrugs in lymphocytes by competitively binding to P-glycoprotein, a product of multidrug resistance gene-1, in vitro. Thus, cyclosporin could be used for the reversal of multidrug resistance, experienced in patients with longterm treated RA.
15383812 The Kudo total elbow arthroplasty in patients with rheumatoid arthritis. 2004 Sep A Kudo total elbow arthroplasty (TEA) was performed in 36 elbows in 35 patients with rheumatoid arthritis. Of those 35, 4 died, 6 prostheses were revised, and 2 were lost to follow-up. Twenty-four elbows with a mean follow-up of 58 months were radiologically and clinically reviewed. Sixteen were scored as excellent by use of the Mayo score and Hospital for Special Surgery 2 score. The mean increase in active motion was 25 degrees. Two humeral and four ulnar radiologic loosenings were noted. Two early dislocations were successfully treated with closed reduction and cast immobilization, two patients used an elbow brace after the closed reduction, and one patient underwent a resection arthroplasty for instability and deep wound infection. Four aseptic loosenings, of which three had an intraoperative fracture at the index operation and one had instability, were revised. Despite initially excellent results, longer follow-up of TEA in rheumatoid patients demonstrated deterioration of the outcome and increased loosening.
12087909 [Current approaches to assessment of rheumatoid arthritis activity]. 2002 AIM: To compare domestic criteria of RA activity and the disease activity scores (DAS). MATERIAL AND METHODS: Russian criteria of RA activity and DAS were used in 99 RA patients. RESULTS: It is shown that RA activity by DAS is higher than when it is assessed by criteria practiced in Russia. CONCLUSION: Further studies are necessary to examine clinical value of DAS criteria.
15794198 beta2-adrenergic receptor gene single-nucleotide polymorphisms are associated with rheumat 2004 The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein-coupled receptors and is present on skeletal and cardiac muscle cells and on lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population and the distributions of single-nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164 are changed in asthma, obesity, and hypertension and in the autoimmune disease myasthenia gravis. An involvement of the beta2-AR has also been suggested in human rheumatoid arthritis (RA) and its animal model. We describe here an increased prevalence of the alleles Arg16 and Gln27 and a lower prevalence of homozygosis for Gly16 and Glu27 in patients with RA. Patients having the genotype combination GlyGly16-GlnGlu27 had higher levels of rheumatoid factor (RF) and a more active disease than other patients. Patients having the genotype Arg16-Gln27+ had higher levels of RF when compared to those having Arg16+Gln27+, and patients who were carriers of Gln27 had a more active disease than non-carriers of Gln27. Our results show an association of beta2-AR SNPs with RA in a population from the northern part of Sweden. Our study also confirms the strong linkage disequilibrium of genotypes at amino acid positions 16 and 27.
11974491 [Basic principles in rheumatologic patient education. Theoretical principles and didactic 2002 Feb Nowadays, the handling of a chronic disease is seen as a process, influenced by a variety of factors. Case studies, taken from health behavior, help to illustrate the conduct of patients suffering from chronic diseases and develop strategies of how to increase a patient's skills in coping with his illness. The concept of self-efficacy beliefs is of great importance and will be discussed in detail. In addition, possible effects of patient education in the comprehensive treatment of rheumatic diseases will be presented. In teaching methods, equal emphasis is placed on the transmission of information as on the development of practical know-how. They are on a par with emotional support, motivation, assistance in accepting the disease and coping with fear. The special methods and media required will be discussed, along with the framework for training methods and qualification required of the staff in charge of training.
14730598 Prognostic markers of radiographic progression in early rheumatoid arthritis. 2004 Jan OBJECTIVE: To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). METHODS: The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. RESULTS: After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. CONCLUSION: Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.
12379528 The F158V polymorphism in FcgammaRIIIA shows disparate associations with rheumatoid arthri 2002 Nov OBJECTIVES: To investigate the association of the FcgammaRIIIA gene with rheumatoid arthritis (RA) in two genetically distinct groups: a white group from the United Kingdom and a northern Indian group. METHODS: The distributions of the two alleles of the FcgammaRIIIA F158V polymorphism were determined in 398 white patients from the United Kingdom and 63 Indian patients with RA and compared with those from 289 United Kingdom and 93 Indian healthy controls, respectively. RESULTS: Among the Indian patients, the frequency of the rare 158V allele and the proportion of 158VV homozygotes were reduced (relative risk (RR)=0.3, 95% confidence interval (95% CI) 0.1 to 1.1, p<0.06), reaching statistical significance for carrying the 158VV phenotype relative to 158FV or FF (RR=0.2, 95% CI 0.05-0.9, p<0.02). Conversely, no significant deviation in allelic frequencies was noted between the patients and controls from the United Kingdom. CONCLUSIONS: The 158VV phenotype showed a weak protective effect against developing RA in the Indian group. However, this sample was small (resulting in a low power for statistical analysis) and no independent confirmation was found in the larger white United Kingdom group. Thus the FcgammaRIIIA locus is unlikely to be of major importance in causing RA.
14970399 Factors influencing the beliefs of patients with rheumatoid arthritis regarding disease-mo 2004 May OBJECTIVE: To investigate factors influencing the beliefs of patients with rheumatoid arthritis (RA) regarding disease-modifying medication. METHOD: Twenty-nine patients with RA either starting a disease-modifying anti-rheumatic drug (DMARD) for the first time or changing DMARD were recruited. Semi-structured interviews, activity diaries and focus groups were conducted over 9 months. A coding framework was developed and data analysed using the constant comparative method to identify key themes. RESULTS: DMARDs were perceived as central to the management of RA but strong concerns were expressed about potential long-term effects. Beliefs about DMARDs were informed by material from a wide range of sources. Judgements of efficacy were influenced by symptom relief, occurrence of side-effects and perception of alternative treatment options. Perception, reporting and tolerance of side-effects differed widely between individuals. The emotional impact of starting and being withdrawn from medication appeared stronger in people with more experience of DMARD use. CONCLUSIONS: Patients have complex and evolving belief systems relating to DMARDs. Understanding these systems will facilitate the provision of appropriate information and effective support not only in decision-making about treatment but also in relation to discontinuing treatment.
12814326 Approaches to identifying genetic predictors of clinical outcome in rheumatoid arthritis. 2003 Predicting which patients with rheumatoid arthritis (RA), at presentation, are likely to suffer a severe disease course based on genotype data would be a major clinical advance. It would ensure that patients at highest risk of a severe outcome could be targeted with early aggressive therapies. With a better understanding of interactions between genotype and drug response it would be possible to prescribe treatments most likely to be efficacious and safe for specific patient subgroups. While a clear genetic component has been demonstrated in RA severity, the identification of genetic factors poses a challenge to researchers in the field. Initiatives such as the SNP Consortium and advances in genotyping technology have facilitated the investigation of genetic factors in both disease susceptibility and severity. However, several other factors, such as the availability of suitable longitudinal cohorts, definition of outcome measures, study design, selection of genetic markers, and statistical power, will all contribute to the likely success of genetic studies. Several strategies that have been applied in the pursuit of genetic predictors of clinical outcome in RA. While some encouraging results have been generated, it has so far been difficult to quantify the predictive value of genetic markers and extrapolate the results from genetic studies to clinic patients. Establishing high quality prospective inception cohorts, a more systemic approach to defining suitable outcome measures, and understanding the effects of treatment, will be critical to the eventual identification of good predictive genetic markers.
11922201 Measuring health related quality of life in patients with rheumatoid arthritis--reliabilit 2002 OBJECTIVE: To adapt the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire for Swedish patients and evaluate psychometric properties in a prospective study. METHODS: Reliability was assessed in 61 patients filling in RAQoL two times with one week's interval. 114 patients completed RAQoL and Nottingham Health Profile (NHP) on 2-3 occasions 6 months apart. Validity was evaluated comparing RAQoL-scores to disease-related variables and NHP subscales. Standardized response mean was applied to calculate responsiveness with the RA-related variables as external indicators of change. RESULTS: Test-retest reliability was high and internal consistency sufficient. RAQoL correlated as expected to NHP section scores. In a multivariate model the Stanford Health Assessment Questionnaire disability index (HAQ) and general health could explain 40% and disease activity measures 13% of the variance of RAQoL. Correlations between change scores of clinical variables and RAQoL and NHP were weak but positive. Standardized response means regarding change of disease activity, HAQ, and general health were small but in the same range for both RAQoL and NHP. CONCLUSION: The Swedish RAQoL had similar measurement properties as the original version. However, responsiveness regarding condition specific measures was not better than for the generic instrument NHP.
12798452 HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis 2003 Jun 1 PURPOSE: To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction. METHODS: Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1. RESULTS: Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01). CONCLUSION: Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.
15547081 Bone mineral density in patients with rheumatoid arthritis: relation between disease sever 2004 Dec OBJECTIVE: To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA). METHODS: We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses. RESULTS: The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients. CONCLUSION: BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.
14604829 Peptidylarginine deiminase type 4: identification of a rheumatoid arthritis-susceptible ge 2003 Nov Recent studies using linkage disequilibrium and SNPs uncovered a rheumatoid arthritis (RA)-susceptible haplotype in the gene encoding peptidylarginine deiminase (PADI) type 4. This gene is one of four known PADI genes that encode enzymes to change arginine into citrulline in proteins. Post-translational modifications of proteins, including peptidyl citrullination, are related to autoimmunity, and peptidyl citrulline is a known target of one of the most RA-specific autoantibodies. Further research on PADI4, its citrullination of native peptides, subsequent breakdown of tolerance, and the role of these peptides in the development of RA, is expected to bring a better understanding of autoimmunity and arthritis, and advancements in the medical care of RA.
12794363 [Anticitrulline antibodies - new marker in rheumatoid arthritis diagnostics]. 2003 The overview provides the knowledge about rheumatoid factor isotypes and their significance in the case of rheumatoid arthritis. New immunological methods have been introduced in the last decade proving their validity in seronegative rheumatoid arthritis. Antikeratin and anticitrulline antibodies were found to be useful diagnostic tools for seronegative and early rheumatoid arthritis. The methods perform well for scientific needs as well as in daily clinical practice.