Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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12649699 | [Arthroscopic synovectomy in chronic inflammatory rheumatism: clinical and functional aspe | 2003 | By now many authors regard arthroscopic synovectomy an integral part of therapeutic treatment of many rheumatic diseases with favourable results on post operating course and clinical picture in the long term. The pathologic synovial tissue during articular inflammatory rheumatism is well known to have a damaging effect responsible of early cartilage injury, as well as symptomatic action (e.g. articular stiffness, effusion, pain, functional limitation). Therefore to value the removal of such a tissue you should think of the secondary prevention of cartilage injury, besides the symptomatic point of view. Since 1996 we performed 190 arthroscopic synovectomy, the adopted criteria of judgement were: pain (spontaneous, during active and passive movements), effusion or swelling presence, articular range and cartilage state (evaluated during arthroscopy according to Outerbridg's classification). 70% of the cases showed good results and six years later the beginning of this activity we retain arthroscopic synovectomy as a valid help in articular inflammatory rheumatism treatment. | |
14703600 | Sjögren's syndrome. | 2003 Dec 30 | Sjogren's syndrome (SS) describes xeropthalmia and xerostomia due to lymphocytic infiltrates of lacrimal and salivary glands. SS may occur alone (primary SS) or in association with several other autoimmune diseases (secondary SS). The clinical features involve a wide variety of organs, including skin, eyes, oral cavity and salivary glands, and systems, including nervous, musculoskeletal, genitourinary and vascular. Sicca symptoms can be found in a number of other disorders including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis, and other rheumatic disorders. | |
12539940 | Results of simultaneous bilateral total knee replacement: a study of 1208 knees in 604 pat | 2002 Fall | Bilateral symptomatic knee arthritis is a common clinical problem. There are conflicting opinions as to the advisability of simultaneous sequential bilateral total knee replacement. Complication rates of primary unilateral knee replacement are well documented and there are several small series that compare the two techniques. The objective of this study was to identify the complication rate of simultaneous sequential bilateral total knee replacement in a large patient population. Over a 13-year period, 604 primary bilateral sequential simultaneous total knee replacements (1208 knees) were performed. Office notes and hospital charts were retrospectively reviewed to obtain age, sex, diagnosis, knee alignment, associated comorbidities, operative protocol, transfusions, and complications. The study results showed 5.1% local and 15.3% systemic complications and 0.7% mortality rate (none in the past 9 years). With appropriate patient selection and operative technique, patients who present with bilateral symptomatic knee arthritis can enjoy the benefits of simultaneous sequential bilateral total knee replacement without increasing their risks of complications. | |
12837047 | Effects of orally administered undenatured type II collagen against arthritic inflammatory | 2002 | Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA. | |
15328423 | Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheum | 2004 Nov | OBJECTIVES: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. METHODS: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking. RESULTS: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l. CONCLUSIONS: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity. | |
16137006 | [Effect of ubiquitin-proteasome pathway on TRAIL inducing apoptosis]. | 2004 Feb | OBJECTIVE: To determine the influence of ubiquitin-proteasome in regulating the TRAIL-mediated apoptosis. METHODS: RASF cells and SCID mice were divided into 4 groups treated with PBS,anti-DR5, lactacystin, and anti-DR5 plus lactacystin. The apoptosis of cells was detected with Hoechst 33342 and TUNEL. The effect of caspase inhibitor on cell apoptosis was analysed with Hoechst 33342 and Luminescent ATP Lite. RESULTS: Block ubiquitin-proteasome with lactacystin, a highly specific and irreversible proteasome inhibitor, induced 95% cell apoptosis both in vitro and in vivo. In contrast, there was no apoptosis of cells after the treatment with anti-DR5 antibody or lactacystin alone. CONCLUSION: The inhibition of ubiquitin-proteasome pathway can sensitize rheumatoid arthritis synovial fibroblast cells to TRAIL- induced apoptosis, and the activation of caspase 8 and caspase 4 is necessary in this process. | |
15729864 | A case of rheumatoid nodulosis successfully treated with surgery. | 2004 Nov | We report the case of a 76 year-old male with multiple subcutaneous nodules, but without joint symptoms or deformities, who was diagnosed histopathologically with rheumatoid nodulosis after resection of the nodules. Rheumatoid nodulosis is a disease characterized by multiple subcutaneous nodules that are histopathologically similar to rheumatoid nodules, a high titer of rheumatoid factor, and radiologically detectable cystic bone lesions, but with none or few of the systemic manifestations orjoint activity of rheumatoid arthritis (RA). It is considered to be a benign variant of RA. This rare disease must be considered when a case of multiple subcutaneous nodules is encountered, even in aged males withoutjoint symptoms or deformities. | |
14579251 | PAD, a growing family of citrullinating enzymes: genes, features and involvement in diseas | 2003 Nov | Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of protein-bound arginine to citrulline. This post-translational modification may have a big impact on the structure and function of the target protein. In this review, we will discuss the effects of citrullination and its involvement in several human diseases, including rheumatoid arthritis and multiple sclerosis. So far, four isotypes of PAD have been described in mammals. We describe the existence of PAD in non-mammalian vertebrates and the existence of a fifth mammalian PAD. In addition, tissue-specific expression, genomic organization and evolutionary conservation of the different PAD isotypes will be discussed in detail. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2003/25/v25.1106.html. | |
12493014 | Variations in immune response genes and their associations with multifactorial immune diso | 2002 Dec | There are three genetic methods often used for detecting genes contributing to susceptibility or resistance to multifactorial diseases: nonparametric linkage analysis, case-control association analysis, and transmission disequilibrium test. In this review, we present the theoretical basis that the case-control association study has the highest power of detecting disease genes if there is no population stratification between patients and controls. Taking advantage of the high power, we have carried out extensive case-control association analyses of candidate genes for the search of susceptibility genes to rheumatic diseases in the Japanese as well as in some other populations. Several new associations have been disclosed, including those of TNFR2, FCGR2B, and CD19 gene polymorphisms with systemic lupus erythematosus, in addition to some unexpected findings such as the common occurrence of NKG2-C null allele in the healthy population. Genome-wide association studies using single nucleotide polymorphisms (SNPs) or microsatellite polymorphisms have become realistic, and development of new high-throughput and cost-effective SNP typing technologies is urgently needed. At the same time, our observations may indicate that the 'classical' candidate gene approach will remain a strong alternative, even in the age of 'post genome-sequence'. | |
11995351 | [Vital capacity rapid inhalation induction (VCRII) technique with sevoflurane for a rheuma | 2002 Apr | Successful airway management in an adult female patient with limited cervical extension and a subluxation of bilateral jaw joints caused by rheumatoid arthritis was reported. We planned to reduce the intensity of pain in her right hand through neurolysis of the ulnar nerve in her right elbow joint. Right axillary nerve blockade with 1% lidocaine 10 ml and 0.25% bupivacaine 10 ml, was employed unsuccessfully to achieve adequate anesthetic effect. Anesthesia was administered using a vital capacity rapid inhalation induction (VCRII) technique with 5% sevoflurane in the oxygen. When the patient lost consciousness, a size 3 laryngeal mask airway (LMA) was inserted under spontaneous breathing on the first trial. There was very little hemodynamic change during the insertion of the LMA. Anesthesia was maintained with sevoflurane 1.5-2.0% in oxygen under spontaneous breathing. Emergence from anesthesia was rapid and no signs of upper airway obstruction were observed after the removal of the LMA. The use of the LMA with VCRII technique and anesthetic maintenance using sevoflurane, are likely to be an optional technique of airway management in patients with problematic airway. | |
15174542 | Wear of the cup in the Charnley LFA in the young patient. | 2004 May | Since wear and loosening of the ultra-high-molecular-weight polyethylene cup are factors which limit the life of an arthroplasty we have attempted to identify factors associated with either low wear (0.02 mm/year or less) or high wear (0.2 mm/year or more). In a series of 1434 Charnley low-friction arthroplasties (1092 patients) 190 (13.2%) showed low wear while 149 (10.4%) showed high wear. We used chi-squared test to assess the significance of various factors. The significant factors of the low-wear group were female gender (p = 0.042), rheumatoid arthritis (p = 0.014), Charnley grade C (p = 0.03) and varus position of the stem (p = 0.003). The use of acetabular cement pressurisation (p = 0.07) and medialisation of the cup (p = 0.07) approached significance. In the high-wear group there was a predominance of men (p = 0.042) with osteoarthritis (p = 0.006) as the underlying hip pathology, and the stem in a valgus position (p = 0.023). Support of the cup by the rim of the acetabulum approached significance (p = 0.07). There was no statistical significance between the two groups for revision for aseptic loosening of the stem or fracture of the stem (p = 0.49). There was a highly significant difference (p < 0.0001) between the two groups for revision for wear and aseptic loosening of the cup, 5.3% compared with 39%. Changes in the cup geometry are probably sufficient to explain the increasing incidence of loosening and revisions with the increasing depth of penetration of the cup. There is much to be gained from the use of a low-wearing ceramic-ultra-high-molecular-weight combination. Tissue reaction to the polyethylene particles cannot be the cause of aseptic loosening of the stem. | |
12634229 | Number needed to treat (NNT): implication in rheumatology clinical practice. | 2003 Apr | OBJECTIVE: To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews. METHODS: The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment. RESULTS: The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite. CONCLUSIONS: The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk. | |
12027526 | Monocyte/macrophage initiation of organ-specific autoimmunity: the ultimate 'bystander' hy | 2002 Apr | It is postulated that organ-specific autoimmune diseases could be initiated by dysregulated peripherally activated monocytes/macrophages penetrating into target organs nonspecifically. Failure of regulation of pro-inflammatory monocytes/macrophages might then result in autoimmune disease if secondary over-expansion of pre-existing autoantigen-specific T cell populations occurs in genetically predisposed individuals. | |
12749017 | Complete recovery from refractory immune thrombocytopenic purpura in three patients treate | 2003 Jun | Management of patients with immune thrombocytopenic purpura (ITP) who have persistent, severe, and symptomatic thrombocytopenia following splenectomy is difficult and empirical. No single agent or regimen provides long-term success for most patients, and for most treatments it is difficult to assess whether benefits outweigh risks. We report three consecutive patients with critical chronic refractory ITP, who responded promptly and completely following treatment with etanercept, an inhibitor of tumor necrosis factor-alpha. These patients had failed 6-11 previous treatments. In the first patient, etanercept was given for its approved indication: a flare of co-existing rheumatoid arthritis. The next two patients were treated with etanercept because of successful outcomes in the previous patients. Although etanercept appeared to be effective treatment for ITP in these 3 patients, the experimental nature of this treatment and the potential risks must be emphasized. On the basis of these case reports, a clinical trial has been initiated to systematically evaluate the efficacy and risks of etanercept in the management of children and adults with chronic ITP. | |
12782016 | The role of COX-2 in angiogenesis and rheumatoid arthritis. | 2003 Jun | Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA. | |
12562402 | T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant r | 2003 Feb | During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-gamma was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease. | |
14558079 | Direct medical costs and their predictors in patients with rheumatoid arthritis: a three-y | 2003 Oct | OBJECTIVE: To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs. METHODS: Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy. RESULTS: The mean total annual direct medical care cost in 2001 for a patient with RA was 9,519 US dollars. Drug costs were 6,324 US dollars (66% of the total), while hospitalization costs were only 1,573 US dollars (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was 19,016 US dollars per year, while the cost for those not receiving biologic therapy was 6,164 US dollars. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were 5,022 US dollars more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years. CONCLUSION: Estimates of direct medical costs for patients with RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs. | |
15297282 | First clinical evaluation of sagittal laser optical tomography for detection of synovitis | 2005 Feb | OBJECTIVE: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. METHODS: 78 SLOT images of proximal interphalangeal joints II-IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. RESULTS: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. CONCLUSION: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE. | |
12021152 | Class II MHC alleles in rheumatoid arthritis in Tamilnadu, India: is there an association? | 2002 Apr | Rheumatoid arthritis (RA) was reported to be associated with class II MHC alleles in different ethnic populations. A similar study was undertaken to determine the association of class II MHC with RA patients of Tamilnadu (Tamil-speaking Hindus), India. Thirty patients with RA and 39 healthy controls were included. Polymorphic second exons of the DRB1, DQA1, and DQB1 genes were amplified and subjected to SSOP typing. No allele was found to be significantly associated with RA. However DRB1*11 (P = 0.01) and DQB1*0302 (P = 0.02) were significantly associated with rheumatoid factor-positive RA patients. (All the DRB1*11-positive RA patients had either *04 or *10 allele as their second allele. This study is first of its kind in this population. | |
11892711 | The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium. | 2002 Jan | OBJECTIVE: Reactive oxygen intermediates play an important role in the inflammatory processes of rheumatoid arthritis. Cyclooxygenase-2 is an inducible form of an enzyme involved in prostanoid biosynthesis. This study linked peroxynitrite (ONOO-) to the signaling pathways that induce COX-2. RESULTS: Exposure of rheumatoid synovial cells to peroxynitrite resulted in COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in peroxynitrite-treated rheumatoid synovial cells. Dexamethasone markedly inhibited this peroxynitrite-mediated COX-2 expression at therapeutic concentrations. CONCLUSION: This study demonstrates that oxidant stress is an important inducer of COX-2 in rheumatoid synovium. This induction may contribute to the amplification of prostanoids in the rheumatoid inflammatory process. |