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ID PMID Title PublicationDate abstract
11817593 Association of baseline levels of urinary glucosyl-galactosyl-pyridinoline and type II col 2002 Jan OBJECTIVE: To evaluate whether measurements of urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II), 2 new markers of destruction of the synovium and cartilage collagen breakdown, respectively, are associated with the progression of joint damage in patients with early rheumatoid arthritis (RA), and to compare this association with that with serum matrix metalloproteinase 3 (MMP-3), a proteinase expressed by synovial tissue and chondrocytes, and that with serum C-reactive protein (CRP), an index of systemic inflammation. METHODS: The prospective study cohort comprised 116 patients with early RA who were part of a large, double-blind, randomized study comparing the efficacy of etanercept and methotrexate. The relationship between baseline levels of urinary Glc-Gal-PYD, urinary CTX-II, and serum MMP-3 and the progression of joint destruction, as measured by changes in the modified Sharp score (average findings of 2 independent readers) over 1 year, was investigated. RESULTS: Levels of urinary Glc-Gal-PYD (+70%), urinary CTX-II (+104%), and serum MMP-3 (+219%) were elevated compared with the levels in 76 healthy controls. The baseline levels of Glc-Gal-PYD (r = 0.30), CTX-II (r = 0.25), and MMP-3 (r = 0.29) correlated with the changes over 1 year in the total Sharp score (joint space narrowing and bone erosion). Patients with baseline levels of Glc-Gal-PYD, CTX-II, and MMP-3 that were higher than the mean + 2 SD in healthy controls had a significantly greater progression of joint damage, with an increase in the total Sharp score over 1 year that was from 3- to 8-fold higher than that in patients with low baseline levels of these markers. Moreover, patients with these higher levels of Glc-Gal-PYD, CTX-II, and MMP-3 had a higher risk of progression of the disease (increase in total Sharp score > or =0.5 units) than did the other patients (relative risks and 95% confidence intervals [95% CI] 3.3 [95% CI 1.5-7.4], 2.5 [95% CI 1.1-5.7], and 2.5 [95% CI 1.1-5.6], respectively). The baseline serum level of CRP was not significantly associated with the progression of joint damage. Adjustment of the levels of Glc-Gal-PYD, CTX-II, and MMP-3 according to radiologic damage at baseline did not alter their association with progression. After adjustment for serum CRP, the relative risk slightly decreased, but remained significant, for Glc-Gal-PYD (2.6 [95% CI 1.1-6.3]). Patients with both increased levels of the molecular markers and radiologic damage at baseline had a higher risk of progression of joint damage than did those with either high molecular marker levels or radiologic damage. CONCLUSION: High baseline levels of Glc-Gal-PYD, CTX-II, and MMP-3 are associated with increased risk of progression of joint destruction over 1 year in early RA. The association between baseline levels of urinary Glc-Gal-PYD and progression of joint erosion was independent of the severity of radiologic damage and inflammation at baseline. Combining the measurements of these molecular markers with radiologic assessment of joint damage may be useful for identifying patients with RA who are at high risk of rapid progression and for whom early aggressive treatment would be beneficial.
12421995 Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthri 2002 Nov OBJECTIVE: Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients. METHODS: Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-kappaB ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption. RESULTS: Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the relative proportion of circulating osteoclast precursors between RA patients and normal controls. Osteoclast precursors in RA patients were not more sensitive to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF or RANKL. Dexamethasone, but not interleukin (IL) 1beta, tumour necrosis factor alpha and IL-6, increased osteoclast formation and lacunar resorption. CONCLUSION: There is an increase in the extent of lacunar resorption carried out by osteoclasts formed from circulating precursors in RA patients. This is not due to an increase in the number of circulating precursors or increased sensitivity to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF, RANKL or inflammatory cytokines. Our findings suggest that increased osteoclast functional activity rather than osteoclast formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteoclast formation and resorption.
11961170 Polymorphism in the immunoglobulin VH gene V1-69 affects susceptibility to rheumatoid arth 2002 Apr OBJECTIVE: To investigate the contribution of polymorphism in the immunoglobulin heavy chain variable region V1-69 gene set to genetic susceptibility to rheumatoid arthritis (RA) in Czech and British patients. METHODS: We used V1-69 gene sequence-specific polymerase chain reaction (PCR) and restriction enzyme digestion to study polymorphism in the V1-69 gene set in germline DNA of 109 Czech and 159 British RA patients and 164 ethnically matched controls. Polymorphism was further studied by nucleotide sequencing of the V1-69 gene locus in germline DNA. RESULTS: We found that all patients and controls had at least one V1-69 gene copy. In the Czech RA cohort, the dimorphic nucleotide in codon 73 of V1-69 (GAA or AAA) was present in the homozygous form 73(A/A) in 31 of 109 (28.4%) RA patients vs 12 of 79 (15.2%) controls [odds ratio (OR)=2.22, P<0.001]. When the RA patients and controls were classified according to HLA shared epitope (SE) status, 73(A/A) was found in 18 of 76 (23.7%) SE(+) patients compared with 13 of 38 (34.2%) SE(-) patients, four of 12 (18.2) SE(+) controls and eight of 57 (14%) SE(-) controls. This suggests that homozygosity for the dimorphic sequence 73(A) contributed to susceptibility to RA in SE(-) Czech individuals (OR=3.2, P<0.001). The most striking observation was that none of the 38 SE(-) Czech patients, compared with 11 of 76 (14.5%) SE(+) RA patients, three of 22 (13.6%) SE(+) and 11 of 57 (19.3%) SE(-) ethnically matched controls, were homozygous for the alternative dimorphic sequence 73(G/G) (OR=9.1, P<0.05). These data, however, were not replicated in a Caucasoid British RA population. CONCLUSION: The dimorphic sequence at codon 73 (73(A/A)) of the V1-69 gene contributes to genetic susceptibility in SE(-) Czech RA patients.
11838838 CD4 coating, but not CD4 depletion, is a predictor of efficacy with primatized monoclonal 2002 Feb OBJECTIVE: Double blind studies were conducted with the anti-CD4 monoclonal antibody (Mab) keliximab in patients with active, stable rheumatoid arthritis (RA), to confirm preliminary evidence of efficacy and safety from open. uncontrolled studies. METHODS: We enrolled 136 and 186 patients into 2 consecutive, randomized, double blind trials, with similar populations [apart from inclusion of disease modifying antirheumatic drug (DMARD)-naïve patients in Study 2]. Patients received 4 weeks intravenous placebo or keliximab [40, 80, 120, or 140 mg twice weekly (bw), or 240 mg once weekly (ow)]. The primary endpoint was the American College of Rheumatology (ACR) 20 response criteria, one week after the end of treatment. RESULTS: ACR 20 response rates in Study I were 19%, 42%, 51%*, and 69%* (*p < 0.05 compared to placebo), with placebo, 40, 80, or 140 mg keliximab bw, respectively. The response rates in Study 2 were 30%, 39%, 46% and 47% with placebo, 80 or 120 mg bw, or 240 mg keliximab ow, respectively. In the 2 studies, there was a dose dependent increase in peripheral blood CD4+ T cell coating with keliximab, but a different pattern of CD4 depletion was seen. While only 12% of keliximab treated patients in Study I had CD4 counts below 250 cells/mm3 at the end of the treatment period, 47% fell below this level in Study 2. Clinical response was not correlated with CD4 depletion, but was correlated with CD4+ T cell coating with keliximab. CONCLUSION: Coating of peripheral blood CD4+ T cells with keliximab, but not CD4 depletion, is a determinant of clinical response.
12228160 Prospective two year follow up study comparing novel and conventional imaging procedures i 2002 Oct OBJECTIVE: To carry out a prospective two year follow up study comparing conventional radiography, three-phase bone scintigraphy, ultrasonography (US), and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examination in detecting early arthritis. The aim of the follow up study was to monitor the course of erosions during treatment with disease modifying antirheumatic drugs by different modalities and to determine whether the radiographically occult changes like erosive bone lesions of the finger joints detected by MRI and US in the initial study would show up on conventional radiographs two years later. Additionally, to study the course of soft tissue lesions depicted in the initial study in comparison with the clinical findings. METHODS: The metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (14 joints) of the clinically more severely affected hand (soft tissue swelling and joint tenderness) as determined in the initial study of 49 patients with various forms of arthritis were examined twice. The patients had initially been divided into two groups. The follow up group I included 28 subjects (392 joints) without radiographic signs of destructive arthritis (Larsen grades 0-1) of the investigated hand and wrist, and group II (control group) included 21 patients (294 joints) with radiographs showing erosions (Larsen grade 2) of the investigated hand or wrist, or both, at the initial examination. RESULTS: (1) Radiography at the two year follow up detected only two erosions (two patients) in group I and 10 (nine patients) additional erosions in group II. Initial MRI had already detected both erosions in group I and seven (seven patients) of the 10 erosions in group II. Initial US had depicted one erosion in group I and four of the 10 erosions in group II. (2) In contrast with conventional radiography, 3D MRI and US demonstrated an increase in erosions in comparison with the initial investigation. (3) The abnormal findings detected by scintigraphy were decreased at the two year follow up. (4) Both groups showed a marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI and US. (5) There was a striking discrepancy between the decrease in the soft tissue lesions as demonstrated by clinical findings, MRI, and US, and the significant increase in erosive bone lesions, which were primarily evident at MRI and US. CONCLUSIONS: Despite clinical improvement and a regression of inflammatory soft tissue lesions, erosive bone lesions were increased at the two year follow up, which were more pronounced with 3D MRI and less pronounced with US. The results of our study suggest that owing to the inadequate depiction of erosions and soft tissue lesions, conventional radiography alone has limitations in the intermediate term follow up of treatment. US has a high sensitivity for depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive in differentiating minute erosions.
14979058 [Role of TNF-alpha and cytokines in the physiopathology of rheumatoid arthritis. Therapeut 2003 Rheumatoid arthritis inflammation process is characterised by the production of soluble mediators with final alteration of cartilage and bone erosions. Etiological factors of RA remain obscure, however intermediate mechanisms are better understood: proinflammatory cytokines belonging to innate as well as adeptive immunity are principal effectors. TNF alpha and IL1 beta are major components of the inflammatory process: TNF alpha is an important stimulus of cells producing inflammatory mediators (cytokines, metalloproteinases, NO, PGE2,...) and IL1 beta mediates cartilage and bone destruction (via secretion of metalloproteinases, decrease synthesis of glycosaminoglycans...). Natural inhibitors of proinflammatory cytokines are also present such as IL1-Ra for IL1 or secreted soluble receptors, sIL1-RI, sIL1-RII, sTNF-RI, sTNF-RII. The level of these inhibitors are increased but not enough to sustain an anti-inflammatory effect. Progress in animal models and in clinical practice has driven to market biological drugs targeted to inhibit TNF alpha and recently IL1 beta. Other cytokines taking place in the inflammatory cascade before TNF alpha and IL1 beta are potential future therapeutic targets such as IL18. Cytokines with anti-inflammatory effect (IL4, IL10, IL13...) can also be used for treatment of RA in association with anti-TNF alpha or anti-IL1 beta.
12203077 Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study w 2002 BACKGROUND: Liver disturbance in rheumatoid diseases results not only from liver disease associated with the rheumatoid diseases themselves but also from various other causes. This study aimed to elucidate the clinical features of liver disturbance in rheumatoid diseases, focusing on the cause of this disturbance. METHODS: A clinicopathological study was performed in 306 patients (106 with systemic lupus erythematosus, 71 with Sjögren's syndrome, 59 with rheumatoid arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis nodosa). RESULTS: Liver disturbance occurred in 43% of these patients and resulted from various causes. Its degree and duration varied from one cause to another. Liver disease associated with rheumatoid diseases was the leading cause of the liver disturbance in these patients and was characterized by mild and transient liver disturbance (maximum alanine aminotransferase [ALT] level during the study period, 68 +/- 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410 +/- 31 IU/ml; duration of liver disturbance, 6 +/- 2 months). Most patients with this type of liver disease showed minimal change in liver histology, although two-thirds of those evaluated by the international scoring system for autoimmune hepatitis (AIH) were classified as "probable" or "definite". Eight of 14 patients with histologically proven chronic hepatitis or cirrhosis were infected with hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered from autoimmune liver diseases. CONCLUSIONS: Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases.
11925920 [Successful use of immunosuppressive agents for the treatment of progressive rheumatoid in 2002 Jan Interstitial pneumonia (IP) is sometimes a fatal complication of rheumatoid arthritis (RA). We describe a patient with progressive rheumatoid interstitial pneumonia, who responded to intravenous intermittent cyclophosphamide (IV-CY) and cyclosporine (CsA). A 62-year-old man with rheumatoid arthritis was admitted to this hospital because of dyspnea. Examinations on admission revealed that he had active RA with vasculitis and IP Initially, he responded to high-dose corticosteroid therapy. A lung biopsy performed after initial corticosteroid therapy revealed diffuse interstitial pneumonia with marked infiltrations of macrophages into the air spaces. On corticosteroid therapy with prednisolone 30 mg/day, the IP became exacerbated and was refractory to the current high-dose steroid treatment. He responded to intravenous cyclophosphamide, but his IP remained unstable. After CsA treatment was started, a clinical remission was obtained. In this case, CsA was the most effective agent tried. Clinical and pathological considerations led us to speculate that activated alveolar macrophages played a crucial role in the pathogenesis of steroid-resistant IP in this patient, and that the clinical remission induced by CsA may have been due to its inhibitory effect on alveolar macrophages.
12419286 Autoantibodies to C-reactive protein is a common finding in SLE, but not in primary Sjögr 2002 Nov The occurrence of antibodies to human C-reactive protein (CRP) was analysed by enzyme-linked immunosorbent assay (ELISA) in 56 patient sera known to contain antibodies to double-stranded DNA (dsDNA) and in 16 sera from patients with primary Sjögren's syndrome (SS), 15 rheumatoid arthritis, 31 Crohn's disease, and 37 ulcerative colitis. Eighty-seven per cent of the patients with anti-dsDNA antibodies had systemic lupus erythematosus (SLE) and the remaining had autoimmune hepatitis. The cut-off for positive anti-CRP test was set at the 95th percentile of 100 healthy blood donors. Twenty of 56 anti-dsDNA sera (36%) and two of 16 SS sera (13%) had antibodies reactive with human CRP, whereas all other samples were negative. Thirteen of 27 SLE patients (48%) were positive on at least one occasion. The sera containing anti-CRP antibodies only reacted with surface-bound antigen, but not with native CRP in solution. In conclusion, we found that autoantibodies to CRP are common in sera from patients with anti-dsDNA antibodies. It is not likely that this explains the relative failure of CRP response in patients with active SLE. However, it cannot be excluded that anti-CRP autoantibodies have other biological potentials of pathophysiological interest in SLE, for instance by binding to CRP deposited on cell and tissue surfaces.
12137712 Infliximab for the treatment of rheumatoid arthritis. 2002 BACKGROUND: Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA. OBJECTIVES: To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis. SEARCH STRATEGY: Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below. SELECTION CRITERIA: All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks. MAIN RESULTS: Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX), 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.9 to 3.3 for ACR 20, 3.6 to 4.8 for ACR 50 and 5.9 to 12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. REVIEWER'S CONCLUSIONS: Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.
15278730 Cavitating pneumonia after treatment with infliximab and prednisone. 2004 Aug Tumor necrosis factor (TNF)-alpha antagonists constitute a novel class of immunomodulating drugs that are used for the treatment of an increasing number of inflammatory disorders. These agents are associated with an increased risk of tuberculosis, but the risk of other infections is less clear. Reported here is the case of a patient who developed cavitary pneumonia after treatment with infliximab (monoclonal TNF-alpha antibodies) and corticosteroids for rheumatoid arthritis. Cryptococcus neoformans was the only pathogen isolated from bronchoalveolar lavage fluid. The patient responded well to fluconazole. The risk of infection after treatment with TNF-alpha antagonists and the possible causative microorganisms are discussed.
14613268 Tumor necrosis factor alpha, its soluble receptor I, and -308 gene promoter polymorphism i 2003 Nov OBJECTIVE: To study tumor necrosis factor alpha (TNFalpha) -308 gene promoter polymorphism and circulating levels of TNFalpha and soluble TNF receptor type I (sTNFRI) in rheumatoid arthritis (RA) patients with and without reactive amyloidosis. METHODS: In a retrospective study, we examined 55 RA patients with biopsy-proven reactive amyloidosis and 55 control RA patients without amyloidosis (matched for age, sex, rheumatoid factor titer, and RA duration). Inflammatory activity was assessed by measuring the erythrocyte sedimentation rate and C-reactive protein level. TNFalpha gene promoter polymorphism was studied using polymerase chain reaction-restriction fragment length polymorphism assay. Cytokine and receptor levels were measured by enzyme-linked immunoassays. RESULTS: Patients with RA and amyloidosis had significantly higher TNFalpha and sTNFRI levels than did the control RA patients. The increased circulating levels of TNFalpha correlated with interleukin-18 levels, but not with the serum amyloid A protein levels or with TNFalpha -308 gene promoter polymorphism (reported to be associated with high TNFalpha levels and certain disease susceptibilities). In the patients with RA and amyloidosis, those with anemia had significantly higher TNFalpha and sTNFRI levels than did those without anemia, and circulating TNFalpha and sTNFRI levels correlated negatively with hemoglobin concentrations. In the patients with RA and amyloidosis, those with nephropathy had significantly higher TNFalpha and sTNFRI levels than did those without nephropathy; in patients with isolated proteinuria (but no creatinine elevation) the TNFalpha level was also significantly increased, indicating that the TNFalpha elevation was not merely a consequence of impaired renal function. CONCLUSION: This study shows that circulating levels of TNFalpha and sTNFRI are significantly increased in RA patients with amyloidosis as compared with control RA patients without amyloidosis and that the increased levels may be implicated in the pathogenesis of certain disease manifestations, including anemia of chronic disease and renal pathology in reactive amyloidosis.
12571631 Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene 2003 Feb Matrix metalloproteinases (MMPs) are believed to be pivotal enzymes in the invasion of articular cartilage by synovial tissue in rheumatoid arthritis (RA). Here, we investigated the effects of gene transfer of tissue inhibitors of metalloproteinases (TIMPs) on the invasiveness of RA synovial fibroblasts (RASF) in vitro and in vivo. Adenoviral vectors (Ad) were used for gene transfer. The effects of AdTIMP-1 and AdTIMP-3 gene transfer on matrix invasion were investigated in vitro in a transwell system. Cartilage invasion in vivo was studied in the SCID mouse co-implantation model for 60 days. In addition, the effects of AdTIMP-1 and AdTIMP-3 on cell proliferation were investigated. A significant reduction in invasiveness was demonstrated in vitro as well as in vivo in both the AdTIMP-1- and AdTIMP-3-transduced RASF compared with untransduced SF or SF that were transduced with control vectors. in vitro, the number of invading cells was reduced to 25% (P<0.001) in the AdTIMP-1-transduced cells and to 13% (P<0.0001) in the AdTIMP-3-transduced cells (% of untransduced cells). Cell proliferation was significantly inhibited by AdTIMP-3 and, less, by AdTIMP-1. In conclusion, overexpression of TIMP-1 and TIMP-3 by Ad gene transfer results in a marked reduction of the invasiveness of RASF in vitro and in the SCID mouse model. Apart from the inhibition of MMPs, a reduction in proliferation rate may contribute to this effect. These results suggest that overexpression of TIMPs, particularly TIMP-3 at the invasive front of pannus tissue, may provide a novel therapeutic strategy for inhibiting joint destruction in RA.
15308530 Relationship between serum hyaluronic acid level and disease activity in early rheumatoid 2004 Sep OBJECTIVES: To measure hyaluronic acid (HA) levels, which are raised in active rheumatoid arthritis (RA), in patients with early RA, and to assess the correlation with clinical and laboratory indices of disease activity and with subsequent radiographic erosive status. PATIENTS AND METHODS: Patients fulfilling ACR criteria were recruited into a prospective cohort within 6 months of disease onset and reviewed every 6 months. An HA binding protein based sandwich ELISA was used to measure HA in 240 sera from 82 patients at regular intervals. RESULTS: Patients had higher HA levels than age matched healthy blood donor controls (median 37.4 v 29.1 ng/ml, respectively, p<0.02), which increased with more prolonged disease. Baseline HA level correlated with measures of disease activity, including swollen and tender joint counts, HAQ, global assessments, ESR, and CRP; was higher in men; and increased with age. There was no relationship with HLA-DRB1 shared epitope or rheumatoid factor status. At 6 and 12 month follow up visits, HA levels were higher in patients who later developed erosions. However, a raised HA level was not a good predictor of erosions. CONCLUSIONS: Serum HA level correlates with clinical and laboratory measures of disease activity in early RA, but is unlikely to be of practical use in clinical practice.
15188325 Latent variable approach to the measurement of physical disability in rheumatoid arthritis 2004 Jun 15 OBJECTIVE: To measure physical disability in rheumatoid arthritis (RA) using a latent variable derived from a generic and a disease-specific self-reported disability instrument and an observer-assessed functional status scale. METHODS: Consecutive patients with RA completed the modified Health Assessment Questionnaire (M-HAQ) and the Short Form 36 (SF-36) physical function scale. An observer assigned a Steinbrocker functional classification. We used principal component factor analysis to extract a latent variable from the 3 scales. We used the Bayesian Information Criterion to compare how well the new latent variable and the 3 primary scales fit the criterion standards of current work status; vital status at 6 years; grip strength; walking velocity; the timed-button test; pain; and joint tenderness, swelling, and deformity. RESULTS: Complete data were available for 776 RA patients. The extracted latent variable explained 75% of the variance in the 3 primary scales. On a scale of 0-100, higher scores representing less disability, its mean +/- SD was 56.4 +/- 22.5. Correlation between the latent variable and the M-HAQ was -0.87; between the latent variable and SF-36 physical function scale was 0.89, and between the latent variable and Steinbrocker class was -0.85. Multivariate models that included the latent variable had superior fit than did models containing the primary scales for the criteria of current working; death by 6 years; pain; joint tenderness, swelling, or deformity; grip strength; walking velocity; and timed button test. CONCLUSION: A latent variable derived from the M-HAQ, the SF-36 physical function scale, and the Steinbrocker functional class provides a parsimonious scale to measure physical disability in RA. The fit of the latent variable to comparison standards is equivalent or superior to that of the primary scales.
12846053 A biologically important single nucleotide polymorphism within the toll-like receptor-4 ge 2003 May BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous condition affecting 1-2% of the population. Genetics account for 30% of disease susceptibility, with one third arising from the Major Histocompatibility Complex. The toll-like receptor 4 (TLR-4) gene which has been mapped to chromosome 9 (9q32-q33) is involved in innate immune recognition with subsequent proinflammatory cytokine release including TNF. A single nucleotide polymorphism (+896A-->G) resulting in the amino acid substitution (Asp299Gly) has been shown to interrupt TLR-4 mediated signalling. OBJECTIVE: We sought to determine if this TLR-4 polymorphism influences susceptibility to rheumatoid arthritis. METHODS: DNA was extracted from 879 healthy controls and 212 rheumatoid arthritis patients recruited from the north of England. Genotyping was performed using a 5' nuclease Taqman allelic discrimination assay. Allele frequencies were compared between the two groups. We also examined whether an association existed in non-carriers of the DRB1 shared epitope alleles. RESULTS: The frequency of the rare allele was 5.9% in the controls and 7% in the patients. Comparison of rare allele carriage between controls and patients revealed no significant difference p = 0.13. This was also the case in shared epitope negative individuals p = 0.92. CONCLUSION: The TLR-4 +896 polymorphism does not appear to influence susceptibility to rheumatoid arthritis.
14768517 Normal pressure hydrocephalus found after anesthesia--a case report. 2003 Dec Normal pressure hydrocephalus (NPH) is characterized by insidious onset and gradual development of the triad of gait disturbance, dementia, and urinary incontinence. Nausea, vomiting, and signs of increased intracranial pressure do not occur. A 71-year-old male patient was scheduled for total knee replacement due to osteoarthritis of right knee joint. No neurological symptoms and signs except mild forgetfulness were detected during physical examination following admission. Due to operational mistakes, the anesthesiologist was informed that the surgery was cancelled just after completion of induction of general anesthesia. The patient was allowed to emerge from anesthesia. Unfortunately, his consciousness became drowsy the next morning. After a series of examinations, he was at last diagnosed as a case of NPH principally by the brain computed tomography scan. So he was scheduled again but this time for vetriculoperitoneal (V-P) shunt. The patient regained consciousness after V-P shunt. From this case, we learned that NPH may remain in concealment in the patients we contacted in our daily practice. A vigilant physician should keep in mind that the presentation of gait disturbance, dementia, and urinary incontinence in a patient may indicate the likelihood of NPH.
12056288 [Early diagnosis of chronic polyarthritis with conventional roentgen imaging]. 2002 Apr Radiographs used to be the gold standard of imaging techniques in rheumatoid arthritis. New imaging techniques allow more detailed examinations of soft tissue changes, the predominant features of early RA. This could change the place of radiography especially in this phase of the disease. The best available radiographic technique is necessary to capture the changes of early RA. Radiographs of both hands and feet are needed for early diagnosis and standardized follow-up. Extent and distribution of indirect signs of arthritis (soft tissue swelling and juxtaarticular osteoporosis) vary with disease activity but can provide important information also for the differential diagnoses. Inter-reader reliability of these changes is low, thus, questioning the validity of these findings. Direct signs of arthritis (erosions and joint space narrowing) are more easy to detect and are used for the quantification of the long-term disease course, in clinical studies, as proof for the disease modifying property of an intervention. Direct signs of arthritis are also found in other diseases, so they are not exclusive signs of RA. Nevertheless a typical radiographic finding in early RA is highly specific and is the most important risk factor for a poor prognosis. Therefore, it serves as the basis for therapeutic decisions, e.g., for an early aggressive treatment. As long as there are no data that the findings with the new imaging techniques are as relevant for prognosis, radiographs cannot be replaced in early RA.
15278756 Alexithymia and anger in patients with fibromyalgia. 2004 Oct Our objective was to delineate the relevance of the personality construct alexithymia and anger-in in patients with fibromyalgia syndrome. Fifty subjects with fibromyalgia syndrome were compared to 20 subjects with rheumatoid arthritis and 42 healthy controls on the measures of anxiety, depression, anger, alexithymia, pain intensity and disability. There was a significant difference on the measures of anxiety and anger between FMS and RA groups, and also between FMS patients and healthy controls. There was a significant difference between FMS patients and healthy controls on the measures of depression, difficulty in identifying feelings subscale of TAS (TAS-dif), and total alexithymia scores. When the severity of pain was controlled for, there was a significant difference on the measures of anger and alexithymia between the FMS and the RA groups. Fibromyalgia patients were more alexithymic than rheumatoid arthritis patients even when the level of depression was controlled for. Anger towards oneself, which is anger-in, was higher in patients with fibromyalgia patients than in the rheumatoid arthritis sample. A stepwise regression model showed that the anger-out scores and the anxiety scores predicted the level of pain severity, and this explained 32% of the variance in the fibromyalgia syndrome group. Although anger-in is consistently higher in fibromyalgia patients, it is the behavioral expression of anger, together with anxiety, that predicts the severity of the pain. The difficulty of identifying feelings, rather than other dimensions of alexithymia, seems to be associated with fibromyalgia.
12107961 [Chloroquine--miscellaneous properties of the antimalarial drug]. 2002 Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.