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ID PMID Title PublicationDate abstract
18468425 [Antibodies to Klebsiella O-antigens in patients with seronegative spondyloarthropaties]. 2006 Mar OBJECTIVES: The pathogenesis of seronegative spondyloarthropathies is still unknown. A microbial etiology has been suggested. The aim of the study was to analyze the antibodies against Klebsiella O-antigens in serum of patients with seronegative spondyloarthropathies. METHODS: 30 patients with seronegative spondyloarthropathies, 20 with rheumatoid arthritis and 20 healthy volunteers were included in the study. The serum antibodies against Klebsiella O1 and O3 antigens were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In serum of patients with seronegative spondyloarthropaties the antibodies against Klebsiella antigen O1 and O3 occur less frequently (6.67%) than in serum of patients with rheumatoid arthritis (35%) and that in serum of healthy subjects (40%). CONCLUSIONS: The results do not confirm the role of LPS in the pathogenesis of seronegative spondyloarthropthies, but on the other hand we could not exclude the concept that it may play an important role.
16163582 [Brachial plexitis and myelitis and herpes-zoster lumbar plexus disorder in patient treate 2005 Sep Infliximab, a chimeric monoclonal antibody, is a TNF-a inhibitor approved for use in refractory rheumatoid arthritis and Crohn s disease. We present the case of a patient affected by severe rheumatoid arthritis who was successfully treated with infliximab. She suffered diverse neurological complications: brachial plexitis, asymptomatic thoracic myelitis with extensive lesions in MRI study, and herpes zoster lumbar plexitis. We review the neurological adverse effects of infliximab (aseptic meningitis, opportunistic germs infections, disseminated herpes zoster) and focus in their potential adverse effect to induce central and peripheral nervous system demyelination.
17057043 Abatacept. 2006 Nov 1 PURPOSE: The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosing, and administration of abatacept are discussed. SUMMARY: Abatacept is the first drug in a new class of agents known as selective costimulator modulators. Abatacept has been shown to decrease tumor necrosis factor (TNF)-alpha, which is important to the inflammatory response. Abatacept inhibits T-cell function but does not deplete T cells. Activated T cells are important in the inflammatory cascade, ultimately leading to joint inflammation and irreversible structural damage. In patients with rheumatoid arthritis, there is chronic inflammation of the synovial tissue lining the joint capsule. Abatacept is indicated for reducing the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients who have had an inadequate response to at least one disease-modifying antirheumatic drug. Studies in adult patients with rheumatoid arthritis have evaluated abatacept in patients with an inadequate response to either methotrexate or TNF-alpha blocking agents. One trial showed that abatacept produced a favorable six-month clinical response in patients who had previously failed to respond to anti-TNF-alpha therapy. In a study of concurrent abatacept and methotrexate therapy, the addition of abatacept produced favorable outcomes in patients who were not adequately responding to methotrexate alone. CONCLUSION: Abatacept, a newly approved agent for the treatment of rheumatoid arthritis, has shown promising results in patients who have had an inadequate response to other treatment modalities. Abatacept therapy should be reserved for patients who have failed other time-tested treatment modalities, including TNF-alpha antagonists. Results from ongoing postmarketing studies will help determine abatacept's place in therapy.
17456462 Psychosocial and reported inflammatory disease correlates of self-reported heart disease i 2006 BACKGROUND: Past and recent research suggests that psychological and biological factors may increase women's risk of coronary heart disease (CHD). This study examined the prevalence and correlates of self-reported heart disease among Jewish women from the Negev, a socio-economically and culturally unique region in south of Israel. METHOD: A cross-sectional design was used. We interviewed over the phone 526 randomly-selected women (mean age: 44.3+/-14.2 years) about background variables (e.g., education), biomedical risk factors (e.g., body mass index or BMI), self-reported inflammatory diseases (rheumatoid arthritis or RA, urinary infections), psychosocial factors (depression, hopelessness, self-esteem, social-support) and self-rated health and heart disease. RESULTS: Prior physician diagnosis of heart disease was reported by 8.2% of women. Age, economic difficulties, diabetes, hypertension, BMI, physical exercise, RA and urinary infections were significantly associated with reported heart disease. Of all psychosocial factors considered, hopelessness and self-esteem significantly distinguished heart disease cases from non-cases. In a multiple logistic regression, poor self-esteem, RA and hypertension were significant independent correlates of self-reported heart disease. CONCLUSIONS: Pending replication with objective measures of heart disease and a prospective design, poor self-esteem and RA may prove to be new CHD risk factors in women.
16513505 Metatarsal head resection in the rheumatoid foot: 5-year follow-up with and without resect 2006 Mar Twenty-nine patients (45 feet) who underwent metatarsal head resections for rheumatoid forefoot deformities were reviewed retrospectively at a mean follow-up of 6.57 years (range, 5-9.3 years). Resections were confined to the lesser metatarsal heads in 16 feet because of a lack of involvement in the first metatarsal head. In the remaining 29 feet, all metatarsal heads were resected. A questionnaire was provided to assess subjective outcomes. Thirty-three feet (73.3%) had no pain or only mild pain, 5 feet (11%) had moderate pain, and 7 (15.5%) had severe pain. Among the 29 feet with panmetatarsal head resections, 5 (17%) required revision of metatarsal stumps at an average follow-up of 55.2 months (range, 17-84 months; standard deviation, 26.88). Among the 16 feet with only lesser metatarsal head resections, 7 (43.75%) required subsequent first metatarsal head resections at an average follow-up period of 33.14 months (range, 13-56 months; standard deviation, 16.54). In conclusion, metatarsal head resection is a simple procedure that gives long-term pain relief in over two thirds of the patients who have rheumatoid forefoot deformities. A high rate of recurrence of pain and subsequent resection of first metatarsal head is noted if it is not resected primarily. We recommend a low threshold for the inclusion of some form of primary reconstruction of the first metatarsophalangeal joint when resection arthroplasty is performed on the lesser toes.
16802343 Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-s 2006 Jul OBJECTIVE: To determine whether interleukin-6 (IL-6) trans-signaling directs the expression of pre-B cell colony-enhancing factor (PBEF) in vitro and in vivo. METHODS: Complementary DNA from rheumatoid arthritis (RA) synovial fibroblasts treated with IL-6 and soluble IL-6 receptor (sIL-6R) was used to probe a cytokine microarray. PBEF regulation by the IL-6-related cytokines, IL-6, sIL-6R, oncostatin M (OSM), IL-11, and leukemia inhibitory factor (LIF) was determined by reverse transcription-polymerase chain reaction analysis. IL-6-mediated STAT-3 regulation of PBEF was determined using a cell-permeable STAT-3 inhibitor peptide. Antigen-induced arthritis (AIA) was induced in wild-type (IL-6(+/+)) and IL-6-deficient (IL-6(-/-)) mice. PBEF and STAT were detected by immunohistochemistry, immunoblotting, and electrophoretic mobility shift assay. Synovial levels of PBEF were quantified by enzyme immunoassay. RESULTS: IL-6 trans-signaling regulated PBEF in a STAT-3-dependent manner. In addition, PBEF was regulated by the IL-6-related cytokine OSM, but not IL-11 or LIF. Flow cytometric analysis of the IL-6-related cognate receptors suggested that OSM regulates PBEF via its OSM receptor beta and not its LIF receptor. The involvement of PBEF in arthritis progression was confirmed in vivo, where induction of AIA resulted in a 4-fold increase in the synovial expression of PBEF. In contrast, little or no change was observed in IL-6(-/-) mice, in which the inflammatory infiltrate was markedly reduced and synovial STAT-1/3 activity was also impaired. Analysis of human RA synovial tissue confirmed that PBEF immunolocalized in apical synovial membrane cells, endothelial cells, adipocytes, and lymphoid aggregates. Synovial fluid levels of PBEF were significantly higher in RA patients than in osteoarthritis patients. CONCLUSION: Experiments presented herein demonstrate that PBEF is regulated via IL-6 trans-signaling and the IL-6-related cytokine OSM. PBEF is also actively expressed during arthritis. Although these data confirm an involvement of PBEF in disease progression, the consequence of its action remains to be determined.
16288073 Dose intensification with infliximab in patients with rheumatoid arthritis. 2005 Dec BACKGROUND: Infliximab, in combination with methotrexate, is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA). While there is anecdotal evidence that many patients beginning infliximab therapy have their dose and/or frequency of infusions increased over time ("dose intensification"), relatively little is known about actual patterns of use in clinical practice. OBJECTIVE: To examine patterns of infliximab use in patients with RA. METHODS: Using a large US healthcare claims database, all patients with RA who initiated infliximab therapy between January 1, 2000, and September 30, 2001, were identified. The date of each patient's first claim for infliximab was identified and designated as the index date; attention was limited to patients who received infliximab for at least one year. Patterns of infliximab use were then examined over the 12-month period following the index date, based on information on paid claims. RESULTS: Fifty-three patients met all entry criteria; the mean age was 61 years, and 81% were women. Twenty-eight percent of patients received >8 infusions over 12 months. The mean dose of infliximab at initial infusion was 296.2 mg; at final infusion, it was 401.9 mg (36% increase). One-half of study subjects had their dose of infliximab increased by > or =30% between the initial and final infusions; one-third had their dose increased by > or =50%. CONCLUSIONS: Many patients with RA beginning treatment with infliximab have their frequency of infusions and/or medication dose increased within the first 12 months.
16249238 Effects of loss of metatarsophalangeal joint mobility on gait in rheumatoid arthritis pati 2006 Apr OBJECTIVE: To evaluate the effects of loss of range of motion (ROM) of the metatarsophalangeal (MTP) joint on the kinematic parameters of walking in rheumatoid arthritis (RA) patients. METHODS: Inclusion of RA patients with inactive disease, no synovitis of the inferior limb and reduced ROM of the MTP joints. Evaluation of the ROM of the MTP dorsal and plantar flexion, and gait analysis using a three-dimensional computerized movement analysis. Calculation of gait parameters and maximal flexion and extension of the hips and knees during walking. Analysis 1 compared the ROM of dorsal and plantar flexion in patients with or without walking pain; 2 compared the gait parameters between patients and controls; 3 investigated a relationship between gait parameters and (i) the ROM of the MTP dorsal and plantar flexion and (ii) the pain at walking; 4 investigated the relationship between the ROM of the MTP dorsal and plantar flexion and maximal flexion and extension of the hip and knee joints during walking. RESULTS: Nine patients and seven controls were included. The MTP ROM was no different in patients presenting with or without pain at walking. The walking velocity was lower and the stride length shorter in patients than in controls. The walking velocity and the stride length were positively related to the MTP dorsal flexion ROM (r(2)=0.75 and 0.67). There was a negative relationship between maximal flexion of the knee and hips during walking and the underlying MTP dorsal flexion ROM (r(2)=0.67 and 0.54). CONCLUSION: In RA patients, reduced MTP dorsal flexion mobility induces changes in the walking parameters, including the kinematics of the overlying lower limb joints. Treatment of an RA-impaired forefoot should focus on MTP mobility as well as on pain.
15866254 Infliximab therapy in established rheumatoid arthritis: an observational study. 2005 May PURPOSE: To investigate the efficacy, toxicity and drug discontinuation rate in an observational study of patients with established rheumatoid arthritis treated with infliximab. SUBJECTS AND METHODS: Between September 1999 and June 2003, we enrolled 84 patients with rheumatoid arthritis who were being treated with infliximab. All patients met the American College of Rheumatology criteria for rheumatoid arthritis and had been refractory to (or did not tolerate) at least two disease-modifying antirheumatic drugs. Patients entering the study had a negative purified protein derivative skin test, were fully informed about the treatment regimen, and were followed up at predefined times according to a standardized protocol. Data concerning infliximab dosage, tolerability, adverse events, concomitant therapy, dosage interval, and drug discontinuation were all recorded. In addition, the clinical and laboratory variables according to the American College of Rheumatology 20% and 50% response criteria and the disease activity score for the 28 joint indices were also recorded. RESULTS: There were 61 women and 23 men with a mean age of 59 +/- 8 years and mean disease duration of 11 +/- 6 years. Seventy-five percent (63/84) were seropositive for IgM rheumatoid factor. After the first year of treatment, 84.5% of patients continued to be treated with infliximab, whereas this percentage was 73% after the second year and 59% after the third year of treatment. The American College of Rheumatology 20% response criteria was met by 59/84 (70%) of patients, and 38/84 (45%) of the patients achieved the 50% response criteria in the first year of treatment. At the second year of therapy, the American College of Rheumatology 20% response criteria were reached by 35/84 (42%) of the patients and the 50% response criteria by 27/84 (32%). At the third year of treatment with infliximab, the American College of Rheumatology 20% and 50% response criteria were achieved by 13/84 (15.5%) and 10/84 (12%) of the patients, respectively. Twenty-eight of eighty-four (33%) patients discontinued infliximab therapy. The risk of drug discontinuation decreased with the concomitant use of methotrexate. The main reasons for drug discontinuation were adverse drug reactions (16/84, 19%), followed by lack of efficacy (9/84, 11%). The main reasons for drug discontinuation due to side effects were immediate hypersensitivity reactions (9/84, 11%) and infections (6/84, 7%). CONCLUSION: Infliximab was found to be an alternative treatment with a relatively acceptable toxicity profile, despite the fact that two patients developed pulmonary tuberculosis. After the third year of therapy, 59% of patients continued to be treated with infliximab. The concomitant use of methotrexate was associated with the continuation of infliximab therapy.
15831771 Clinical pharmacokinetics of etanercept: a fully humanized soluble recombinant tumor necro 2005 May Etanercept, a fully humanized soluble recombinant tumor necrosis factor receptor fusion protein, is an approved treatment for rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. Etanercept is absorbed slowly from the site of subcutaneous injection, with time to peak concentration at approximately 48 to 60 hours, and is cleared slowly from the body with a t(1/2) of 70 to 100 hours. The absolute bioavailability of etanercept was 58% in healthy subjects following subcutaneous administration. The 25-mg twice-weekly dosage regimen generates systemic exposures comparable to 50 mg once weekly, as predicted by pharmacokinetic modeling and simulation and later confirmed by clinical studies. The pharmacokinetics of etanercept in patients with rheumatoid arthritis are comparable to those in healthy individuals and patients with ankylosing spondylitis, congestive heart failure, and psoriasis. In children with polyarticular-course juvenile rheumatoid arthritis, after subcutaneous doses of 0.4 mg/kg twice weekly, the clearance of etanercept may be slightly reduced in children aged 4 to 8 years. Pharmacokinetic simulation predicts that a dose of 0.8 mg/kg once weekly generates comparable systemic exposure as 0.4 mg/kg twice weekly. No requirement for etanercept dosage adjustment is needed when etanercept is coadministered with warfarin, digoxin, or methotrexate.
16447238 Risk genotypes in folate-dependent enzymes and their association with methotrexate-related 2006 Feb OBJECTIVE: Methotrexate (MTX) is an antifolate agent that is often associated with toxicity. This study investigated whether risk genotypes for folate-dependent enzymes are associated with the toxicity of MTX in patients with rheumatoid arthritis (RA). METHODS: Blood was collected for analysis in a muticenter, cross-sectional study of RA patients who had been receiving MTX for at least 1 month prior to enrollment, and side effects occurring at the time of a single study visit were recorded. Low-penetrance risk genotypes in methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide transformylase (ATIC) 347GG, and serine hydroxymethyltransferase (SHMT1) 1420CC were measured and summed to constitute the toxicogenetic index specific to each patient. Statistical analyses consisted of logistic regression models with clustered-center effects, and associations with risk genotypes were expressed as adjusted odds ratios (ORs). RESULTS: Among 214 patients enrolled at 4 study sites, a total of 67 patients (31%) presented with a side effect (gastrointestinal event, headache, lethargy, alopecia, cough, or dyspnea). Risk genotypes associated with side effects in the central nervous system were MTHFR 677TT (OR 3.3, P < 0.01) and SHMT1 1420CC (OR 2.4, P < 0.05). ATIC 347GG was associated with gastrointestinal side effects (OR 3.0, P < 0.01), while TSER*2/*2 (OR 5.4, P < 0.01) and SHMT1 1420CC (OR 3.2, P < 0.01) were associated with alopecia. The toxicogenetic index ranged from 0 to 3 (median 1). An index of 3 was associated with an approximately 7-fold higher likelihood of having a side effect compared with an index of 0 (P < 0.01). CONCLUSION: These data suggest that a composite index of the cumulative risk genotypes in folate-dependent enzymes may be an effective means of profiling RA patients who develop side effects to MTX.
16846535 Differential expression, function and response to inflammatory stimuli of 11beta-hydroxyst 2006 Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Expression, activity and function of 11beta-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11beta-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-alpha or IL-1beta (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-gamma was without effect, and there was no difference in 11beta-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production--a characteristic feature of synovial derived fibroblasts--was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11beta-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11beta-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation.
16014681 Up regulated expression of tumour necrosis factor {alpha} converting enzyme in peripheral 2005 Aug BACKGROUND: Systemic sclerosis (SSc) is accompanied by abnormalities in humoral and cellular immune systems. OBJECTIVE: To determine the genes specifically expressed in the immune system in SSc by analysis of the gene expression profile of peripheral blood mononuclear cells (PBMC) from patients with SSc, including those treated with haematopoietic stem cell transplantation (HSCT). Additionally, to investigate the clinical significance of the up regulation of tumour necrosis factor alpha (TNFalpha) converting enzyme (TACE). METHODS: PBMC from patients with SSc (n = 23) and other autoimmune diseases (systemic lupus erythematosus (SLE, n = 16), rheumatoid arthritis (RA, n = 29)), and from disease-free controls (n = 36) were examined. Complementary DNA arrays were used to evaluate gene expression of PBMC, in combination with real time quantitative polymerase chain reactions. TACE protein expression in PBMC was examined by fluorescence activated cell sorter (FACS). RESULTS: In patients with SSc 118 genes were down regulated after HSCT. Subsequent comparative analysis of SSc without HSCT and healthy controls indicated SSc-specific up regulation for three genes: monocyte chemoattractant protein-3 (p = 0.0015), macrophage inflammatory protein 3alpha (p = 0.0339), and TACE (p = 0.0251). In the FACS analysis, TACE protein was mainly expressed on CD14(+) monocytes both in patients with SSc and controls. TACE expression on CD14(+) cells was significantly increased in patients with early SSc (p = 0.0096), but not in those with chronic SSc, SLE, or RA. TACE protein levels in SSc monocytes correlated with the intracellular CD68 levels (p = 0.0016). CONCLUSIONS: Up regulation of TACE expression was a unique profile in early SSc, and may affect the function of TNFalpha and other immunoregulatory molecules.
17075835 Glycan analysis of monoclonal antibodies secreted in deposition disorders indicates that s 2006 Nov OBJECTIVE: To compare the glycosylation of polyclonal serum IgG heavy chains in a patient with rheumatoid arthritis (RA) with that of monoclonal serum IgG heavy chains in the same patient during an episode of heavy-chain deposition disease (HCDD), to establish whether glycosylation processing is specific for subsets of B cells. METHODS: Serum IgG was purified using a HiTrap protein G column. Immunoglobulins were run on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels, and IgG glycans were isolated from gel bands and fluorescently labeled. Glycans were analyzed by normal-phase high-performance liquid chromatography and by liquid chromatography-electrospray ionization-mass spectrometry. RESULTS: The glycosylation of serum immunoglobulins from a patient with seronegative RA and HCDD was analyzed. The predominant immunoglobulin was a truncated glycosylated gamma3 heavy chain, and a small amount of polyclonal IgG was also present. The glycan profile showed that the monoclonal gamma3 heavy chain contained fully galactosylated biantennary glycans with significantly less fucose but more sialic acid than in IgG3 from healthy controls. In contrast, the polyclonal IgG showed an RA-like profile, with a predominance of fucosylated biantennary glycans and low levels of galactosylation. The glycan profile of serum IgG obtained from the same patient during disease remission resembled a typical RA profile. CONCLUSION: These data indicate that different types of B cells process a particular set of IgG glycoforms.
16447234 Apoptosis of rheumatoid synovial cells by statins through the blocking of protein geranylg 2006 Feb OBJECTIVE: To determine whether statins induce apoptosis in rheumatoid arthritis (RA) synoviocytes. METHODS: The effects of lipophilic and hydrophilic statins (fluvastatin and pravastatin, respectively) on the apoptosis of cultured RA synoviocytes were examined in vitro. Apoptosis was analyzed by flow cytometry after staining with JC-1 (to measure the mitochondrial transmembrane potential), active caspase 3, annexin V, and propidium iodide. Add-back experiments were conducted to determine which downstream products of the mevalonate pathway could suppress apoptosis. Modulation of various signaling pathways induced by statins, including protein prenylation, was also investigated. RESULTS: Fluvastatin, but not pravastatin, induced apoptosis in RA synoviocytes in a concentration-dependent (1-10 microM) and time-dependent (48-96 hours) manner. Another lipophilic statin, pitavastatin, displayed almost the same effects as fluvastatin. In sharp contrast, lipophilic statins did not significantly increase apoptosis in synoviocytes from patients with osteoarthropathy. Apoptosis induced by fluvastatin was mitochondrial- and caspase 3-dependent and was abrogated by mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. In addition, the geranylgeranyl transferase inhibitor GGTI-298 mimicked the effect of fluvastatin on RA synoviocytes. Treatment of RA synoviocytes with the RhoA kinase inhibitor Y-27632 caused apoptosis. Fluvastatin decreased the amount of RhoA protein in the membrane fraction, but increased the amount in the cytosolic fraction. CONCLUSION: Fluvastatin induced apoptosis in RA synoviocytes through a mitochondrial- and caspase 3-dependent pathway and by the blockage of mevalonate pathways, particularly through the inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathways. These findings suggest that lipophilic statins have potential as novel therapeutic agents for RA.
16134725 Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheum 2005 May OBJECTIVES: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease (CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). METHODS: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms (SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. RESULTS: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. CONCLUSIONS: These data suggest that CARD15 variants are not associated with RA susceptibility.
16688934 Matrix metalloproteinases MMP-3 and MMP-1 levels in sera and synovial fluids in patients w 2005 Sep OBJECTIVES: To investigate whether serum levels of matrix metalloproteinases (MMP-3, stromelysin) and (MMP-1, collagenase) are specifically elevated in joint disease as rheumatoid arthritis (RA) compared to osteoarthritis (OA), and to assess how these markers reflect the clinical activity of RA compared to circulating cytokine as tumor necrosis factor-alpha (TNF-alpha) as well as established variables as [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)]. SUBJECTS AND METHODS: This study included 22 patients with RA, 10 patients with OA and 10 healthy control subjects matched for age and sex. Patients with superimposed infection were excluded. Serum levels of MMP-3, MMP-1, TNF-alpha and CRP were assayed. Synovial fluid (SF) levels of MMP-3 and MMP-1 were also assayed. RESULTS: Serum levels of TNF-alpha and CRP in RA patients were significantly higher than normal subjects. Serum MMP-1 was significantly elevated in patients with RA and OA, compared to healthy controls but there were no significant differences between patients with RA and those with OA. Serum MMP-3 levels did not differ between OA patients and normal sera. However, RA patients displayed significantly elevated levels of this enzyme, compared to OA and control sera. Levels of MMP-3 and MMP-1 in the SF of RA patients were significantly higher than in OA fluids. CRP, ESR, TNF-alpha and MMP-3 correlated significantly with the swollen joint count. The strongest positive correlations existed between rheumatoid activity as assessed by the levels of CRP and circulating levels of MMP-3. Similar correlations between TNF-alpha concentration and CRP, MMP-1 and MMP-3 were observed in RA patients. Serum levels of MMP-3 correlated significantly with serum concentrations of MMP-1 in RA patients (r = 0.487, p < 0.05). There was close correlation between serum and SF concentrations of MMP-3 in RA patients (r = 0.619, p < 0.01). In the same patients there was highly significant correlation between SF concentrations of MMP-3 and MMP-1 (r = 0.732, p < 0.001). CONCLUSIONS: Our data suggested that elevated MMP-3 levels reflected disease activity of RA better than cytokine levels. However, MMP-3 levels do not exceed the association of CRP with clinical activity.
16173246 Inclusion criteria as widely used for rheumatoid arthritis clinical trials: patient eligib 2005 Sep OBJECTIVE: To identify the proportion of patients fulfilling the inclusion criteria widely used in most clinical trials for rheumatoid arthritis (RA)--including the recent clinical trials of anti-Tumor Necrosis Factor alpha (TNFalpha) agents--in a Turkish cohort. METHODS: 186 consecutive RA patients attending a routine tertiary rheumatology clinic were evaluated in 2 groups: Early RA group (group E): 31 patients with a disease duration of < or = 3 years (mean: 1.9 +/- 0.9 years); late RA group (group L): 155 patients with a disease duration of > 3 years (mean: 13.3 +/- 8.6 years). Patients were evaluated according to 2 different sets of inclusion criteria: (i) The widely used common inclusion criteria for RA clinical studies, as outlined by Sokka and Pincus; (ii) the criteria of two major anti-TNF clinical studies, ERA and ATTRACT. RESULTS: No patients in group E, and 9 (6%) patients in group L fulfilled the common criteria used in clinical studies for RA. In group E, 28 patients had already been started on methotrexate; 2 patients were on sulphasalazine and one patient was on leflunomide. Nevertheless, even if the criterion for previous use of methotrexate was not applied patients did not fulfill the rest of the criteria of ERA study. In group L, 9 out of 155 patients (6%) met the criteria for the ATTRACT study. CONCLUSION: Only few patients met the widely used inclusion criteria for most RA clinical trials and the recent clinical trials of TNFalpha agents in this Turkish cohort. This may be explained by the milder disease activity in this geographical region, which further emphasizes the need to consider development of new criteria for inclusion in clinical trials.
15968151 The role of popliteal lymph nodes in differentiating rheumatoid arthritis from osteoarthri 2005 Apr OBJECTIVE: We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also wanted to investigate the relationship between the popliteal lymph nodes and the inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed, three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. MATERIALS AND METHODS: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73 with OA) was analyzed. A lymph node was defined as being 'observed' if it could be seen in at least two planes of the three orthogonal reformatted planes. The number of observed lymph nodes, the mean of the smallest dimension of each lymph node and the existence of central fatty change were recorded. The OA group was graded according to the ISV calculated by a segmentation method: grade I was < 20 cm(3); grade II ranged from 20 cm(3) to 40 cm(3); and grade III was > 40 cm(3). Statistical analysis of the number and the mean size of the popliteal lymph nodes among the four groups (the RA group and the grade I-III OA groups) was performed. RESULTS: The prevalence of the observed popliteal lymph nodes was significantly different between all the OA groups or between the grade III OA group and the RA group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The number (mean +/- standard deviation) of lymph nodes in the grade I OA group, the grade II OA group, the grade III OA group and the RA group was 1.2 +/- 0.4, 1.2 +/- 0.4, 1.3 +/- 0.5, and 2.7 +/- 1.1, respectively. The mean size (mean +/- standard deviation) of the lymph nodes was 3.8 +/- 1.0 mm, 3.6 +/- 1.1 mm, 4.1 +/- 0.8 mm, and 5.4 +/- 1.3 mm, respectively. The incidence of central fatty changes was significantly lower in the RA group than in all the OA groups and the grade III OA group. When differentiating RA from OA, and when the differentiation was confined to the RA group and grade III OA group, respectively, the criteria of the number of lymph nodes, their size, their central fatty change and a combination of all these three criteria showed statistical significance (Az values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001, respectively). CONCLUSION: The number, size and central fatty changes in the popliteal lymph nodes observed on the MR images might serve as simple and useful markers in differentiating RA disease from OA disease. These markers would be particular helpful in cases of severe synovial enhancement where the ISVs of both RA and OA overlap. The number and mean size of the lymph nodes also correlated well with the ISV.
16487688 A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid 2006 May Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.