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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16194697 | The need for tighter rheumatoid arthritis control in a South African public health care ce | 2005 Oct | OBJECTIVE: Medical facilities are restricted in public health care centers in South Africa and patients that enroll in these centers are socioeconomically deprived. We investigated the impact of rheumatoid arthritis (RA) on disability in both a public health care and a private care center. METHODS: The disability index of the Health Assessment Questionnaire (HAQ-DI) and an extensive range of disease and non-disease-related patient characteristics were recorded in 359 RA subjects, 196 public care and 163 private care patients. We compared the data between both patient groups and identified potential predictors of the HAQ-DI by univariate and multivariable logistic regression analysis. RESULTS: The median (range) HAQ-DI was 1.625 (0 to 3) in the public care patients and 0.500 (0 to 3) in the private care patients (P < 0.0001). As compared with private care patients, public care patients were more often African (P < 0.0001) and of mixed ancestry (P < 0.01) and less often White (P < 0.0001). Public care patients also had higher current disease activity scores (P < 0.0001) (except for tender joint counts and the erythrocyte sedimentation rate), higher cumulative disease activity or disease severity scores (joint deformities) (P < 0.0001), a higher frequency of tuberculosis (P < 0.01), and were more often treated with prednisone (P < 0.0001). In multivariable logistic regression models, a HAQ-DI of >1 was independently predicted by current disease activity (swollen joint count) (P < 0.004), cumulative disease activity (joint deformities) (P < 0.005), being under public care (P < 0.008), and prednisone use (P < 0.04). Racial differences were not independently predictive of disability. CONCLUSION: Results of disease outcome measurements were poorer in our public care patients than in our private care patients. Facilities that allow for tighter disease activity control of RA are needed in South African public care centers. | |
16687338 | Long term results of arthrodesis of the wrist: a 6-15 year follow up of 35 patients. | 2006 | A total of 40 wrists in 35 patients were investigated 10.5 (range 6-15) years after arthrodesis. The most common diagnosis was rheumatoid disease. There were 21 Mannerfelt, and 21 plate, arthrodeses. The patients were assessed clinically and up-to-date radiographs obtained. Two Mannerfelt arthrodeses had failed to fuse. Pain during the last week before review and total satisfaction with the operation were excellent in 28 and 30 wrists, respectively. The mean score on the "Disability of arm, shoulder and hand" (DASH) questionnaire was 38 (range 2-75). Plate arthrodeses gave better results than Mannerfelt arthrodeses for all variables studied. Wrists plated in dorsal extension gave the best scores for function and strength. We conclude that either method gives good long term results. Although few of the individual differences were statistically significant, we think that fusion with plates, and in particular plates with dorsal extension, is preferable. | |
17216012 | [Does magnetic resonance represent the future in the follow-up of arthritis?]. | 2006 Oct | Several studies suggest that MRI is between 2 and 10 times superior to conventional radiology in the visualization of erosions. This higher sensibility is dependent on the specific joint assessed, the precocity of the disease, and the timing of follow-up. In addition, MRI can depict bone oedema, which is an early and reversible bone lesion, and evaluate the degree of inflammation of the synovial membrane. A single examination could therefore evaluate disease activity and damage. The sensitivity to change of articular MRI is good, as demonstrated by a number of follow-up studies. In view of these advantages, it may be surprising that MRI has not yet become the gold standard of imaging of the arthritic joint. The three main reasons are low availability of high field machines, examination's costs, and lack of standardization of the technique. Low field extremity-dedicated MRI machines are probably the answer to the first two concerns. They have been shown to obtain reliable results for the clinician, and to be relatively cheap and patient-friendly, allowing repeated follow-up examinations. As far as standardization is concerned, there are many studies addressing the problem, with OMERACT as the driving force. MRI is likely to represent the future of the follow up of arthritis for the evaluation of its pace of progression and the effect of treatment. The advent of new and potent biologic therapies has incremented the need for more sensible imaging methods and will probably drive their diffusion in clinical practice. | |
15880602 | Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a su | 2005 May | OBJECTIVE: To identify rheumatoid arthritis (RA) susceptibility genes in a Japanese population by conducting a large-scale case-control association analysis and linkage disequilibrium (LD) mapping on chromosome 7q31-34, a candidate susceptibility locus identified in a preliminary genome-wide scan in 53 Japanese families, using single-nucleotide polymorphisms (SNPs). METHODS: We prepared 728 dense, evenly spaced SNPs with a minor allele frequency >0.15 in each gene locus on chromosome 7q31-34. Using these SNPs, a 2-stage case-control analysis was performed on 760 RA patients (157 men and 603 women) and 806 non-RA controls (189 men and 617 women). Haplotypes and LD mapping results were assessed based on SNP genotypes in 380 controls. RESULTS: Forty-eight SNPs showed allele associations (P < 0.05) in the first set of DNA samples (380 RA cases and 380 non-RA controls; first-stage analysis). For 4 of the SNPs in the SEC8L1 gene, the association was replicated (P < 0.05) in the second, independent set of DNA samples (an additional 380 RA cases and 380 non-RA controls; second-stage analysis). When data from the 2 groups were combined, the most significant allele association was observed with SNP 441, an intronic SNP of the SEC8L1 gene (P = 0.000059). The SEC8L1 SNPs with significant allele associations were all located in a single conserved LD block (block 4). Haplotype analysis revealed the disease-risk (P = 0.0015) and disease-protective (P = 0.0000062) haplotypes. Resequencing of coding exons within block 4 did not identify any nonsynonymous SNPs. Real-time quantitative polymerase chain reaction revealed that SEC8L1 was expressed ubiquitously in human tissues, including fibroblast-like synoviocytes from RA patients. CONCLUSION: Our locus-wide association and LD analyses identified intronic SNPs and haplotypes in the SEC8L1 gene that are strongly associated with RA. We propose that SEC8L1, which encodes a component of the exocyst complex, is a candidate susceptibility gene for RA in the Japanese population. | |
16164225 | [OPG, anti-rANKL antibody]. | 2005 Sep | Identification of RANKL/ODF (receptor activator of NF-kappaB ligand/osteoclast differentiation factor), RANK(receptor activator of NF-kappaB) and OPG/OCIF(osteoprotegerin/ osteoclastogenesis inhibitory factor) revealed the mechanisms regulating osteoclast differentiation and function. RANKL-RANK signaling is essential for the physiological osteoclast development and plays a major role in the pathological bone destruction. OPG and anti-RANKL antibody act as a specific inhibitor of RANKL and are useful and applicable to osteoporosis and rheumatoid arthritis. | |
16960930 | Comparison of tacrolimus and mizoribine in a randomized, double-blind controlled study in | 2006 Nov | OBJECTIVE: To compare the efficacy and safety of tacrolimus and mizoribine in patients with rheumatoid arthritis (RA). METHODS: Adult patients with RA with an insufficient response to at least one disease modifying antirheumatic drug (DMARD) were randomized to receive 28 weeks of double-blind treatment with tacrolimus 3 mg once daily or mizoribine 50 mg three times daily. The primary efficacy endpoint was the American College of Rheumatology 20% (ACR20) response. Safety was evaluated by adverse events. RESULTS: A total of 204 patients were enrolled for study (103 in the tacrolimus group, 101 in the mizoribine group). Significantly more patients receiving tacrolimus achieved an ACR20 response compared with mizoribine (48.5 vs 10.0%, respectively; p = 0.001). Tacrolimus was also superior to mizoribine in ACR50 and ACR70 response rate, tender and painful joint counts, swollen joint counts and patient and physician assessments of pain, disease activity, and patient's physical function assessment based on the Modified Health Assessment Questionnaire (p < 0.001). Adverse events were more frequent in the tacrolimus group than the mizoribine group (65.0 vs 59.4%); however, there were no statistically significant differences between treatment groups. CONCLUSION: Tacrolimus improves RA symptoms to a significantly greater extent than mizoribine in patients with RA inadequately controlled with at least one prior DMARD. Tacrolimus has the potential to be a useful and highly effective treatment for RA. | |
16378106 | [Relationship between HLA-DR4/1 subtypes and T cell responses to type II collagen or anti- | 2005 Dec 18 | OBJECTIVE: To investigate the relationship between HLA-DR4/1 subtypes and T cell responses to type II collagen or anti-CII 263-272 antibodies. METHODS: Peripheral blood mononuclear cells and sera were obtained from 70 rheumatoid arthritis (RA) patients. T cell proliferative responses to CII 263-272 were evaluated by [(3)H] thymidine incorporation assay. Antibodies specific to CII 263-272 were determined by ELISA. HLA-DR4/1 subtypes were analyzed by PCR-SSP. RESULTS: In HLA-DR4/1 positive group, T cell proliferative responses to CII 263-272 were observed in 55.6% RA patients and anti-CII 263-272 antibodies were present in 66.7% RA patients. In HLA-DR4/1 negative group, T cell proliferative responses to CII 263-272 were observed in 30.3% RA patients and anti-C II 263-272 antibodies were present in 34.8% RA patients. The number of positive antibodies to CII 263-272 or T cell proliferative responses to CII 263-272 in HLA-DR4/1 positive group were higher than in negative group. CONCLUSION: There is a relationship between HLA-DR4/1 subtypes and T cell responses to CII 263-272 or anti-CII 263-272 antibodies. | |
15818671 | Reduced p53 in peripheral blood mononuclear cells from patients with rheumatoid arthritis | 2005 Apr | OBJECTIVE: Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. This profile includes, at least in part, a collection of underexpressed genes that encode proteins that inhibit cell cycle progression and stimulate apoptosis. We aimed to determine whether this gene expression profile confers functional liability on lymphocytes from patients with rheumatoid arthritis (RA). METHODS: Viability studies in response to a panel of proapoptotic stimuli revealed that T lymphocytes from patients with RA were resistant to gamma radiation-induced apoptosis, a process known to be dependent on p53. To assess p53 function in RA peripheral blood mononuclear cells, baseline levels of p53 protein and TP53 transcript were measured in patients with RA and controls. The cellular p53 response to gamma radiation was also assessed by immunoblotting. RESULTS: Lymphocytes from patients with RA had lower baseline levels of TP53 messenger RNA (mRNA) and p53 protein than did those from control subjects and were deficient in their ability to increase p53 after exposure to gamma radiation. A subgroup of patients with RA had a second biochemical defect characterized by expression of very low baseline levels of checkpoint kinase 2 mRNA and protein. CONCLUSION: We conclude that defects in the expression of TP53 mRNA and, in a subgroup, defects in expression of CHK2 mRNA, lead to severe defects in apoptosis in patients with RA. We hypothesize that this liability may contribute to autoimmunity. | |
16029612 | [Identification of biomarkers in serum of early rheumatoid arthritis by proteomic methods] | 2005 May 18 | OBJECTIVE: To discover the biomarkers of early rheumatoid arthritis (RA) patients and healthy person were analyzed by proteomic methods to discover serum biomarkers. METHODS: Samples of peripheral blood were collected form 10 newly diagnosed active RA patients, 5 males and 5 females, aged 54.3 +/- 12.78, with a disease course of 4.08 +/- 1.9 months, and 10 age and sex matched healthy persons. The samples were divided into 10 groups containing 1 sample of patient serum and 1 sample of healthy serum to undergo. High-molecular-weight protein (HMWP) was enriched by depletion of albumin with HiTrap Blue column and depletion of immunoglobulin G with HiTrap rProtein A column. Low-molecular-weight protein (LMWP) was enriched by C18 absorbent binding and elution. After comparative proteomic analysis, the different protein spots were identified using matrix-assisted laser desorption ionization-time of flight-ionization-mass spectrometry. (MALDI-TOF-MS). RESULTS: Marrow-related protein (MRP) 14, a protein of the S100 family was 100% positive in the RA patient sera and 100% negative in the sera of the healthy controls. MRP8, another protein of the S100 family, was 100% positive in the RA patient sera and 50% positive in the sera of the healthy controls. Ubiquitin was 90% positive in the RA patient sera and 10% positive in the sera of the healthy controls. The levels of apolipoprotein A-I (ApoA-I), serum amyloid A1 and A2 (SAA1/SAA2), and transthyretin of the RA patients were all significantly higher than those of the healthy controls. CONCLUSION: MRP14/MRP8, SAA1/SAA2 and ubiquitin may play important roles in development of RA and their determination may benefit early diagnosis, evaluation of disease activity and investigation of new therapy targets. | |
17043867 | The complex role of Fcgamma receptors in the pathology of arthritis. | 2006 Dec | Autoantibodies of the IgG class and the immune complexes they form are central players in the pathology of rheumatoid arthritis (RA). Receptors for the Fc part of IgG, FcgammaR constitute one of the main effector mechanisms through which IgG immune complexes exert their action. The different members of the FcgammaR family exhibit extensive structural homology leading to redundancy in ligand specificity and signal transduction. Moreover, the initiation of effector mechanisms by IgG immune complexes can also be mediated by the complement system. This strong redundancy and high degree of complexity hampers a direct in vivo analysis of antibody effector pathways. Over the last decade, mice deficient for different combinations of FcgammaR have been generated by gene targeting. These knockout mice provide excellent tools to define the specific contribution of the different FcgammaR to IgG effector pathways in well-established in vivo mouse models for arthritis. This review will discuss the results of the studies that analyze the role of the different members of the FcgammaR family in murine arthritis models and their implications for our understanding of the human disease. | |
16903811 | Spondyloarthropathy: an independent risk factor for kidney stones. | 2006 Aug | PURPOSE: To better stratify risk and to verify previous prevalence reports, we conducted a retrospective cohort study comparing the lifetime incidence of nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA). PATIENTS AND METHODS: Patients with SpA or rheumatoid factor-positive RA were identified from the rheumatology clinics of two Veterans Affairs hospitals and the University of Minnesota. Among them, 168 were confirmed to meet the American College of Rheumatology criteria and gave informed consent to participation. They were sent a survey regarding their rheumatologic diagnosis, coexistent conditions, medications, and history of kidney stones. Of the total, 143 patients responded and met the criteria for analysis. Rheumatoid arthritis patients were age and sex matched with SpA patients as controls. RESULTS: Populations were similar in all categories except that RA patients were more likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) = 5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85 patients was found to be reliable on imaging review (sensitivity 82%; specificity 100%). CONCLUSIONS: Self-reporting of kidney stones by patients is a reliable measure. Despite adjusting for medication use and matching two similar arthritic populations, patients with SpA had a higher incidence of kidney stones than those with RA. This finding suggests that SpA is an independent risk factor for nephrolithiasis. Future studies will evaluate urinary risk factors and polymorphisms in the ANKH gene that may predispose to stone formation in this high-risk group. | |
16380915 | Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 sa | 2005 Dec | Candidate-gene association studies in rheumatoid arthritis (RA) have lead to encouraging yet apparently inconsistent results. One explanation for the inconsistency is insufficient power to detect modest effects in the context of a low prior probability of a true effect. To overcome this limitation, we selected alleles with an increased probability of a disease association, on the basis of a review of the literature on RA and other autoimmune diseases, and tested them for association with RA susceptibility in a sample collection powered to detect modest genetic effects. We tested 17 alleles from 14 genes in 2,370 RA cases and 1,757 controls from the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) collections. We found strong evidence of an association of PTPN22 with the development of anti-citrulline antibody-positive RA (odds ratio [OR] 1.49; P=.00002), using previously untested EIRA samples. We provide support for an association of CTLA4 (CT60 allele, OR 1.23; P=.001) and PADI4 (PADI4_94, OR 1.24; P=.001) with the development of RA, but only in the NARAC cohort. The CTLA4 association is stronger in patients with RA from both cohorts who are seropositive for anti-citrulline antibodies (P=.0006). Exploration of our data set with clinically relevant subsets of RA reveals that PTPN22 is associated with an earlier age at disease onset (P=.004) and that PTPN22 has a stronger effect in males than in females (P=.03). A meta-analysis failed to demonstrate an association of the remaining alleles with RA susceptibility, suggesting that the previously published associations may represent false-positive results. Given the strong statistical power to replicate a true-positive association in this study, our results provide support for PTPN22, CTLA4, and PADI4 as RA susceptibility genes and demonstrate novel associations with clinically relevant subsets of RA. | |
15971425 | Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern of invasiv | 2005 May | OBJECTIVE: In rheumatoid arthritis (RA) the synovial membrane proliferates and invades the underlying tissues. The cell-associated fibrinolytic system (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation. For this reason, the expression and the role of such enzymatic system was investigated in synovial fibroblasts (SF) of normal and RA patients. METHODS: In SF obtained from RA patients and control subjects, uPA, uPAR and PAI-1 were measured by ELISA of cell lysates and culture medium and by RT-PCR of mRNAs. uPA was also studied by zymography. Proliferation was measured by cell counting and cell invasion with the Boyden chamber. RESULTS: RA-SF over-express uPAR and PAI-1 and are more prone than the normal counterpart to spontaneous and uPA-challenged invasion and proliferation, which are counteracted by antagonists of the fibrinolytic system. CONCLUSIONS: RA-SF display the fibrinolytic pattern and behaviour of invasive tumor-like cells. Antagonists of the fibrinolytic system are able to revert growth and invasion of both normal and RA-SF. | |
17075826 | Investigation of the MHC2TA gene, associated with rheumatoid arthritis in a Swedish popula | 2006 Nov | OBJECTIVE: A recent study of rheumatoid arthritis (RA) showed an association with a functional single-nucleotide polymorphism (SNP) mapping to the promoter region of the MHC2TA gene on chromosome 16p13 in a Swedish population. Interestingly, evidence for linkage to this region has been detected previously in a subgroup of UK RA families carrying 2 copies of shared epitope (SE) alleles. Therefore, we undertook this study to investigate the association of the MHC2TA gene promoter with RA in a UK Caucasian population. METHODS: Association with 5 SNPs spanning the promoter region of the MHC2TA gene was investigated in 813 UK RA patients and 532 population controls. Association with a functional putative RA-causal polymorphism (-168*G/A [rs3087456]) was tested in a total of 1,401 UK RA patients and 2,475 controls. Genotyping was performed using a Sequenom MassArray platform. Estimated haplotype frequencies were generated using the expectation-maximization algorithm and compared between patients and controls. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. No evidence for association was found, either with the putative RA-causal polymorphism (-168*G/A) or with the other SNPs tested. Haplotype analysis revealed extensive linkage disequilibrium across the promoter region but no evidence for association. Stratifying the data set by carriage of SE alleles did not alter the conclusions. CONCLUSION: A functional polymorphism of the MHC2TA gene locus previously associated with RA in a European population has not been associated with RA in a UK population. These findings do not provide support for the notion that this gene plays a major role in the etiology of RA. | |
16893535 | Growth hormone, VEGF and FGF: involvement in rheumatoid arthritis. | 2007 Jan | Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown etiology, is characterized by dysfunctional cellular and humoral immunity, enhanced migration and attachment of peripheral macrophages and pro-inflammatory leukocytes to the synovium and articular cartilage of diarthrodial joints. The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression, synovial neovascularization, proteinase-mediated dissolution of articular cartilage matrix and osteoclast-mediated subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with manifestations similar to adult RA that occurs in childhood. JCA usually causes precocious joint destruction and often also presents with evidence of growth plate anomalies and reduced stature. Three proteins play an integral role in both adult RA and JCA. These are somatotropin (also called pituitary growth hormone (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). GH is responsible for regulating long bone growth and skeletal maturation through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis by hepatocytes. Mechanisms responsible for growth plate disturbances and short stature in children with JCA include deficient GH production, GH-insensitivity resulting from defects in the GH receptor, suppressed IGF-1 synthesis or neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition, GH has also been implicated in perpetuating inflammation and pain in adult RA. VEGF has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis resistance in adult RA. | |
16906016 | HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. | 2006 Sep | OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells from healthy individuals and non-MTX-treated RA patients were activated with different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10 production was investigated by specific immunoenzymatic assay. HLA-G 14-bp polymorphism genotyping was performed in healthy individuals and RA patients, defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G1 concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients has confirmed an increase of the -14/-14 bp genotype in the responder group (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26-4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that the MTX induces the production of the anti-inflammatory sHLA-G molecules that concur with the therapy response. Furthermore, the association between -14/-14 bp genotype and MTX clinical outcome proposes this polymorphism as a therapy marker in the early phases of the disease. | |
16320848 | [Clinical application of omega-3-fatty acids (cod-liver oil)]. | 2005 | A range of prospective studies have proven high efficacy of omega3-polyunsaturated fatty acids (omega3-FA, cod-liver oil (CLO)) in secondary prophylaxis of atherosclerosis and its complications. Monotherapy with CLO or its combination with statines in natients with hypertriglyceridemia substantially lowers triglyceride level. Due to their anti-inflammatory properties, including the capability of prostaglandin production reduction, clinical application of omega3-FA is indicated in high risk of preterm delivery, and in patients with rheumatoid arthritis. In the latter CLO application allows reduction of the dose of nonsteroidal anti-inflammatory drugs, and improves chief clinical symptoms (reduces pain and morning joint stiffness.) | |
16521366 | Biologic therapies in autoimmune diseases. | 2006 Jan | Over the past decade, the treatment of rheumatoid arthritis has been revolutionised by the development of therapies targeted at molecules involved in driving the inflammatory response. This review briefly summarises the established uses of biologic therapies in rheumatoid disease, and outlines other diseases in rheumatology and other fields where biologic agents are finding a role. | |
16555468 | Intravenous application of omega-3 fatty acids in patients with active rheumatoid arthriti | 2006 Jan | The objective of this work was to assess the therapeutic efficacy and tolerability of intravenously applied n-3-PUFA in patients with active rheumatoid arthritis (RA). Thirty-four patients with active RA [identified as having a DAS28 (disease activity score including a 28 joint count) > 4.0] were enrolled into this 5-wk open pilot study (one group design). From the time of screening (visit 0, or V0), background therapy had to remain unchanged. Patients received 2 mL/kg (= 0.1-0.2 g fish oil/kg) fish oil emulsion intravenously on 7 consecutive days (Visit 1-Visit 2, or V1-V2) in addition to their background therapy. A decrease of the DAS28 > 0.6 at day 8 (Visit 2) was the primary efficacy measure. Moreover, the DAS28 at day 35 (Visit 3, or V3), the modified Health Assessment Questionnaire, the American College of Rheumatology (ACR) response criteria (V2, V3) and the Short Form-36 (V3) were assessed. Thirty-three patients completed the trial. The mean DAS28 at V1 was 5.45;at V2, 4.51 (P < .001 V1-V2) and at V3, 4.73 (P < .001 V1-V3; V2-V3, not significantly different). Of the 34 patients, 56% achieved a reduction of the DAS28 > 0.6 at V2 (mean 1.52); 27% > 1.2. At V3, 41% of the patients showed a DAS28 reduction > 0.6 (mean 1.06), and 36% > 1.2. ACR 20 and 50% responses at V2 were seen in 29 and 12% of patients, respectively; at V3, the comparable values were 18 and 9%, respectively. Overall tolerability was excellent. Intravenous application of n-3-PUFA (as an add-on therapy) was considerably well tolerated and led to improvement of the disease activity status in a reasonable number of RA patients. Future trials are warranted to answer whether the intravenous application of n-3-PUFA constitutes a therapeutic option in RA patients. | |
15641964 | Salivary gland and temporomandibular joint involvement in rheumatoid arthritis: relation t | 2005 Jan | OBJECTIVES: To study temporomandibular joint (TMJ) involvement, salivary gland dysfunction and oral mucosal lesions in rheumatoid arthritis (RA), and to investigate the relationship to general disease activity. SUBJECTS AND METHODS: The TMJ dysfunction index (D(i)), mean salivary flow and disease activity score (DAS28), were calculated for 50 RA-patients, and 23 non-RA patients (controls). RESULTS: Median D(i) was 5.5 (range: 0-21) for the RA-patients compared with 2.0 (range: 0-9) for the controls (P < 0.0001). Pain on movement of the TMJ (P = 0.015), muscular pain (P = 0.006), TMJ pain (P = 0.019) and D(i) as a total (P = 0.009), significantly correlated with DAS28. Mean resting whole saliva (RWS) flow was 2.6 (s.d. 2.4) ml per 15 min for the RA-patients and 4.5 (s.d. 3.0) for the controls (P = 0.003). RWS correlated positively with haemoglobin (P = 0.021) and negatively with Westergren erythrocyte sedimentation rate (ESR) (P = 0.029). No major differences in frequency of oral mucosal lesions were seen between RA-patients and controls. CONCLUSIONS: Higher frequency of TMJ and salivary gland dysfunction in RA-patients compared with controls has been demonstrated. RA disease activity is associated with hyposalivation and TMJ dysfunction. |