Browse

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

ID PMID Title PublicationDate abstract
17965425 Influence of age and gender on the 28-joint Disease Activity Score (DAS28) in rheumatoid a 2008 Aug OBJECTIVES: To investigate the influence of age and gender on the components of the 28-joint Disease Activity Score (DAS28) in patients with rheumatoid arthritis (RA), and to clarify whether a high DAS28 can be equally interpreted in all age groups, independent of gender. METHODS: A prospective cohort of 553 patients with RA was studied for approximately 20 years after diagnosis. The single measures of disease activity and the share of different components of the DAS28 (eg, erythrocyte sedimentation rate; ESR) were analysed and compared between three age groups (<45, 45-65 and >65 years) and per gender, using analysis of variance (ANOVA). The performance of the DAS28 and its components was explored in moderate to high and low DAS28 categories. Linear mixed model analysis was used to design the models best predicting ESR and the share of ESR. RESULTS: ESR significantly increased with age, independent of other variables of disease activity. This increase was more pronounced in male than in female patients. Nevertheless, the share of ESR increased with age only in male patients with a low DAS28 (<3.2). If the DAS28 score was >3.2, age and gender did not have a significant effect on any components of the DAS28. C-reactive protein (CRP) and DAS28(CRP) were not influenced by age. CONCLUSIONS: A high DAS28 was found to perform equally in all age groups, in men and women, despite the elevating effect of age on ESR. In elderly men with low disease activity, remission rate could be underestimated by an elevated ESR.
17183621 The economic burden of rheumatoid arthritis in a developing nation: results from a one-yea 2007 Jan OBJECTIVE: To assess annual direct and indirect costs in a prospective cohort of patients with rheumatoid arthritis (RA) in Thailand from the societal perspective. METHODS: Data on costs and intangible losses were prospectively collected at regular intervals over a one-year period from 158 RA patients who attended a major tertiary care facility in Bangkok, Thailand. Direct medical, direct nonmedical, indirect, and total costs were estimated according to patients' respective health insurance conditions and converted to 2001 US dollars using published purchasing power parity estimates. Sensitivity analyses were performed and the predictors of costs and intangible losses were investigated. RESULTS: The average societal cost of RA was estimated to be 2682 US dollars, 41.4% of patients' average annual income. Average direct and indirect costs were estimated to amount to 2135 US dollars and 547 US dollars per patient per year, respectively. Seventy-three patients (46.2%) experienced at least one event of intangible losses and 46 patients (29.1%) had decreased earnings ability because of RA. Poor physical function, joint deformity, high number of disease modifying antirheumatic drugs, and steroid use contributed to higher costs and presence of intangible losses. CONCLUSION: RA consumes a significant proportion of patients' annual average incomes and poses a significant economic burden to society. Since RA mainly affects a working-age population, early and timely treatment of this disease can improve both the suffering and the economic productivity of patients in Thailand.
17064872 Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patie 2006 Dec Lymphadenopathy, which may be associated with systemic symptoms, is frequently associated with rheumatoid arthritis (RA). Reactive non-neoplastic tissue comprises the majority of the lymph node lesions. However, several cohort studies have demonstrated that RA has an increased risk of non-Hodgkin's lymphomas (NHLs). Since the early 1990s, an atypical or malignant lymphoproliferative disorders (LPD) in patients immunosupressed with methtorexate (MTX) therapy for RA has been emphasized, namely MTX-associated LPDs. Epstein-Barr virus (EBV) has received attention in connection with the etiology of RA. The present review describes the clinicopathologic and immunohistochemical findings of reactive, atypical and malignant LPDs associated with RA along with the presence or absence of EBV in LPDs using the in situ hybridization (ISH) method. The majority of reactive lymph node lesions exhibit reactive follicular hyperplasia with interfollicular polyclonal plasmacytosis. Atypical LPDs rarely appears in RA patients. However, these cases occasionally pose difficult problems in the differential diagnosis from malignant lymphomas associated with RA or atypical and malignant LPDs showing RA-like clinicopathological findings. Clinicopathologically, three types of atypical LPDs have delineated, i.e. (i) resembling multicentric Castleman's disease (MCD); (ii) atypical paracortical hyperplasia with lymphoid follicles (APHLF) and; (iii) atypical lymphoplasmacytic immunoblastic proliferation. Malignant lymphoma associated with RA is characterized by; (i) predominance of elderly cases; (ii) usually female predominance, reflecting the sex ratio of RA; (iii) longstanding history of RA; (iv) relatively frequent advanced stage of disease; (v) majority of the patients had the B-cell phenotype; and (vi) an increased frequency of diffuse large B-cell lymphoma (DLBCL) in RA. It is unlikely that EBV is the causative agent of either reactive or atypical LPD. Among malignant lymphomas, EBV-associated lymphoma comprised only a small fraction of all NHLs in the general RA patient population.
18178691 Orthopaedic surgery in patients with rheumatoid arthritis over 20 years: prevalence and pr 2008 Oct OBJECTIVE: To study the prevalence of orthopaedic surgery and to evaluate possible predictive factors for large joint replacements in patients with early rheumatoid arthritis (RA). PATIENTS AND METHODS: A cohort of 183 patients (116 (63.4%) female) with early RA was monitored for 16-20 years after recruitment during 1985-9. Mean (SD) age of patients 51.4 (12.4) years; mean (SD) duration of symptoms before inclusion 12 (7) months and mean (SD) duration of follow-up 16 (4) years. Occurrence of orthopaedic surgery was recorded continuously. A first prosthesis of a large joint (shoulder, elbow, wrist, hip, knee or ankle) was used as outcome variable in the predictive analyses. RESULTS: In total, 386 orthopaedic interventions were performed in 106/183 (58%) patients during follow-up and a large joint replacement was performed in 44/183 (24%) patients. Using a Cox regression model, it was shown that Health Assessment Questionnaire, C-reactive protein and erythrocyte sedimentation rate at inclusion, and radiographic changes in small joints after 1 year, were associated with an increased risk of receiving prosthesis of large joints. CONCLUSION: In this cohort of patients with RA monitored from early disease stage, orthopaedic surgical procedures were performed in more than half of the patients. This included first large joint replacements in 24% of the cases. Easily available measures were identified as predictors of such joint replacements. This study could serve as a reference for comparison with cohorts of patients with RA recruited today, in which new more efficacious treatments are used.
17445440 [Membrane and cytoplasmic expression of urokinase-type plasminogen activator receptor in s 2007 Feb OBJECTIVE: To investigate the production of membrane-expressed urokinase-type plasminogen activator receptor (muPAR) and cytoplasmic-expressed uPAR (cuPAR) in synovial tissue from patients with rheumatoid arthritis (RA) and analyze their relationship with the severity of synovial inflammation in RA. METHODS: MuPAR and cuPAR were measured with indirect immunofluorescence (IIF) and immunoperoxidase histochemical analysis of the synovial tissue sections from 18 patients with RA, 10 patients with osteoarthritis (OA) and 4 healthy subjects. The association of uPAR expression with the severity of synovitis in RA was then analyzed. RESULTS: MuPAR positive cells were detected in approximately (66.0+/-9.4)% of the RA synovial cells, distributed predominantly in vascular endothelial cells and fibroblast cells. While cuPAR positive cells were found in about (61.0+/-5.8)% of the RA synovial cells, including subsynovial and interstitial macrophage-like cells, mononuclear leukocytes and fibroblast cells. Both the muPAR and cuPAR expression were much more increased in RA synovial tissue than those in OA synovial tissue. Furthermore, the number of muPAR (r=0.672, P<0.01) and cuPAR (r=0.649, P<0.01) positive cells in synovial tissue was also found to be correlated significantly with the severity of synovial inflammation in RA patients. CONCLUSION: The up-regulated expression of muPAR in synovial vascular endothelial cells suggests an important role of this molecule in angiogenesis in RA and the increased production of cuPAR in synovial inflammatory cells indicates the involvement of cuPAR in the inflammatory process in RA.
16716286 Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab th 2006 Oct OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.
18947379 Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid a 2008 Rheumatoid arthritis is a multisystemic auto-inflammatory disease affecting up to 1% of the population and leading to the destruction of the joints. Evidence exists for the involvement of the innate as well as the adaptive immune systems in the pathology of the disease. The success of anti-tumour necrosis factor-alpha indicates the importance of pro-inflammatory mediators produced by innate immune cells in rheumatoid arthritis progression. Therefore, considerable efforts have been made in elucidating the signalling pathways leading to the expression of those mediators. This review will concentrate on the role of signalling pathways in innate immune cells in the context of rheumatoid arthritis.
17468978 Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rhe 2007 Aug Apoptosis is reduced in the synovial tissue of patients with rheumatoid arthritis (RA), possibly due to decreased expression of pro-apoptotic genes. Programmed Cell Death 5 (PDCD5) has been recently identified as a protein that mediates apoptosis. Although PDCD5 is down-regulated in many human tumors, the role of PDCD5 in RA has not been investigated. Here we report that reduced levels of PDCD5 mRNA and protein are detected in RA synovial tissue (ST) and fibroblast-like synoviocytes (FLS) than in tissue and cells from patients with osteoarthritis (OA). We also report differences in the PDCD5 expression pattern in tissues from patients with these two types of arthritis. PDCD5 showed a scattered pattern in rheumatoid synovium compared with OA, in which the protein labeling was stronger in the synovial lining layer than in the sublining. We also observed increased expression and nuclear translocation of PDCD5 in RA patient-derived FLS undergoing apoptosis. Finally, overexpression of PDCD5 led to enhanced apoptosis and activation of caspase-3 in triptolide-treated FLS. We propose that PDCD5 may be involved in the pathogenesis of RA. These data also suggest that PDCD5 may serve as a therapeutic target to enhance sensitivity to antirheumatic drug-induced apoptosis in RA.
16763464 Osteoclasts, rheumatoid arthritis, and osteoimmunology. 2006 Jul PURPOSE OF REVIEW: Osteoclasts are terminally differentiated cells of the monocyte/macrophage lineage that resorb bone matrix. Bone destruction in rheumatoid arthritis is mainly attributable to the abnormal activation of osteoclasts, and studies on activation of osteoclasts by the immune system have led to the new research field called osteoimmunology. This interdisciplinary field is very important to biologic research and to the treatment of diseases associated with the bone and immune systems. RECENT FINDINGS: The T-cell-mediated regulation of osteoclast differentiation is dependent on cytokines and membrane-bound factors expressed by T cells. The cross-talk between receptor activator of nuclear factor-kappaB ligand and interferon-gamma has been shown to be crucial for the regulation of osteoclast formation in arthritic joints. Recent studies indicate that an increasing number of immunomodulatory factors are associated with the regulation of bone metabolism: nuclear factor of activated T cells c1 has been shown to be the key transcription factor for osteoclastogenesis, the activation of which requires calcium signaling induced by the immunoglobulin-like receptors. SUMMARY: New findings in osteoimmunology will be instrumental in the development of strategies for research into the treatment of various diseases afflicting the skeletal and immune systems.
18087762 Evaluation of lateral instability of the atlanto-axial joint in rheumatoid arthritis using 2008 Jul Upper cervical involvement is common in patients with rheumatoid arthritis (RA). Anterior atlanto-axial subluxation (aAAS) sometimes occurs at an early stage of the disease. We hypothesized that not only antero-posterior instability but lateral instability may occur with atlanto-axial involvement in RA. To prove this hypothesis, we evaluated the lateral instability of the atlanto-axial joint in RA, using dynamic open-mouth view radiographs. Thirty RA patients and a control group of 22 non-RA outpatients were enrolled in this study. The patients underwent lateral view radiographs of the cervical spine during flexion and extension, and antero-posterior (AP) open-mouth views during maximum right and left bending of the neck. The anterior atlanto-dental interval (AADI) was measured to evaluate antero-posterior instability of the atlanto-axial joint, and atlanto-dental lateral shift (ADLS) was defined to evaluate dynamic lateral instability. In the RA group, AADI averaged 3.2 mm in flexion, and in eight patients, it exceeded 3 mm in flexion (aAAS). In the control group, the AADI averaged 1.0 mm in flexion. The ADLS in the RA group averaged 14.8%, and this was significantly greater than in the control group, in which it averaged 6.1%. The ADLS averaged 20.6% in the RA subgroup with aAAS, and 12.7% in the RA subgroup without aAAS. In both subgroups, the ADLS was significantly greater than that of the control group. In this study, dynamic lateral instability of the atlanto-axial joint in RA was demonstrated. The results suggest that an evaluation of the dynamic lateral instability of the atlanto-axial joint can be useful for early diagnosis of atlanto-axial lesions in RA.
16465613 Rheumatoid arthritis: links with cardiovascular disease and the receptor for advanced glyc 2006 Jan Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), altered coagulation, and cyclooxygenase (COX)-2 inhibitors will be covered in brief. The receptor for advanced glycation end products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA. As has been the case with many novel molecules, functional polymorphisms are thought to alter disease expression and assist us in coming to terms with the biological activities of the parent molecule. The review will conclude with a discussion of the potential role of the RAGE Glycine 82 Serine polymorphism.
16249825 The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoi 2006 Jul The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.
16504992 Are American College of Rheumatology 50% response criteria superior to 20% criteria in dis 2006 Dec OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.
16837491 Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan. 2006 Dec OBJECTIVE: To determine the risk for tuberculosis infection in patients with rheumatoid arthritis before the anti-cytokine era in Japan. PATIENTS AND METHODS: A database of a single-institute-based large observational cohort study for rheumatoid arthritis at the Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan, was analysed. Information on the history of tuberculosis infection was collected by patient self-reporting during April and October 2003. The age-adjusted incidence rate and relative risk for tuberculosis infection were investigated. RESULTS: Among 5044 patients with rheumatoid arthritis, 483 (9.6%) patients claimed to have a history of tuberculosis infection before October 2002. The frequency of history of tuberculosis increased according to the age of the patient. Four cases of new-onset tuberculosis were identified among 5544 patients with rheumatoid arthritis during 1 year. The age-adjusted incidence of tuberculosis was 42.4/100,000 patients. The relative risk for tuberculosis was 3.21 (95% confidence interval (CI) 1.21 to 8.55), and that of men and women was 10.59 (95% CI 3.42 to 32.78) and 1.41 (95% CI 0.2 to 10), respectively. CONCLUSION: There was an increased risk of tuberculosis infection in Japanese patients with rheumatoid arthritis, especially in male patients before the introduction of anti-tumour necrosis factor treatment. These data should form the basis for the risk management of anti-cytokine treatment in Japan.
17704927 [International classification of functioning, disability and health and its significance f 2007 Nov The international classification of functioning, disability and health (ICF) has been developed by the World Health Organization (WHO) to describe health and handicaps in more detail in order to allow better classification and registration. The ICF comprises the disease, structure, functioning, activity and participation as well as corresponding factors related to the individual and the environment. By this means an integrated concept and assessment of biologic, individual and social aspects of health is attained. The ICF represents an essential addition to the international classification of diagnoses (ICD) and procedures (OPS). The ICF consists of two interelated parts. The first part that describes functioning and disability contains two components: one related to the body (functioning and structure) and one related to activity and participation. The second part describes the context factors (related to the environment and the individual). Body functions are the physical and mental functions of the organism. Body structures are the anatomically defined parts of the body. Activity describes how a task is solved or how an action can be performed and participation is the way in which an individual is involved in the environment and society. The ICF categories make the classification of all aspects of functioning and health in individuals easier and independent of diseases or specific assessment instruments. However, since there are more than 1,400 categories, the ICF cannot be used in daily practice in this form. Therefore, attempts are made to identify those parts of the ICF that are relevant for specific patients, situations and disease states or activities. These are the so-called ICF core sets. This article attempts to give an overview on the ICF, to provide an insight into recent work on the ICF related to musculoskeletal and rheumatic diseases and, finally, to describe how an ICF core set for patients with acute arthritis was made possible by means of a successful multicenter cooperative effort.
15975970 Standardisation of synovial tissue infiltrate analysis: how far have we come? How much fur 2006 Jan Changes in cellular infiltrate and expression of cytokines, chemokines, and cell adhesion molecules as a result of therapeutic interventions in rheumatoid arthritis can be demonstrated in the synovial membrane. However, before synovial tissue analysis can be used as an outcome measure in such studies, standardisation of the site and method of synovial tissue acquisition, methods of tissue processing, and appropriate methods of detection and measurement of cell lineage specific markers and relevant biological proteins is needed.
18026898 Radiological study of joint destruction patterns in rheumatoid flatfoot. 2008 Jun The purpose of this study was to clarify variations in patterns of flattening in rheumatoid hindfoot. Out of 232 outpatients with rheumatoid arthritis treated at our hospital from 2001 to 2003, we studied lateral radiographs of feet of 216 patients (423 weight-bearing views). We measured the medial arch angle (MAA) and talar angle (TA) and compared the alignment of the talonavicular joint-sagittal plane of each foot. We also evaluated the relationship between the severity of flattening and inclination of the talus and performed cluster analysis. Three groups were clustered by MAA and TA. In group I, joints were normal or close to normal. In group II, both talonavicular and subtalar joints were affected. In group III, talonavicular joints were minimally affected, and the subtalar joints were primarily affected. Groups II and III were thought to be a different pattern of flattening. The present results suggest that there are at least two patterns of flattening in rheumatoid hindfoot.
17448247 Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rh 2007 Apr 20 BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. METHODS: Using an enzyme-linked immunosorbent assay (ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. RESULTS: Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score (r = 0.13, p = 0.12). CONCLUSION: In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice.
18447591 Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthriti 2008 May BACKGROUND: In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA. OBJECTIVE: To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects. METHOD: This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition. CONCLUSION: We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.
17214933 [Predictive role of diagnostic information in treatment efficacy of rheumatoid arthritis b 2007 Jan OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven patients were included in the clinical trial from 9 clinical centers. They were randomly divided into Western medicine (WM) treated group, 194 cases; and traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete physical examination and 18 common clinical manifestations were prepared before the randomization and after the treatment. The WM therapy included voltaren extended action tablet, methotrexate and sulfasalazine. The CM therapy included Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment. The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation. All data were analyzed on SAS 8.2 statistical package. The relationships between each variable and efficacy were analyzed, and the variables with P<0.2 were included for the data mining analysis with neural network model. All data were classified into training set (75%) and verification set (25%) for further verification on the data-mining model. RESULTS: Eighteen variables in CM and 24 variables in WM were included in the data-mining model. In CM, morning stiffness, swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint pain were positively related to the efficacy, and disease duration and more urination at night negatively related to the efficacy. In WM, erythrocyte sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint stiffness and swollen joint were positively related to the efficacy, and yellow fur in tongue, red tongue, white blood negatively related to the efficacy. In the analysis with the neural network model in the patients of verification set, the predictive response rates of 20% patients would be 100% and 90% in the treatment with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on the full clinical trial data with collection of both traditional Chinese medicine and modern medicine diagnostic information, shows a good predictive role for the information in the efficacy in rheumatoid arthritis.