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ID PMID Title PublicationDate abstract
16882591 Low-field MRI for assessing synovitis in patients with rheumatoid arthritis. Impact of Gd- 2006 Jul OBJECTIVE: To investigate the impact of a double dose compared to a single dose of contrast material in low-field magnetic resonance imaging (MRI) on semi-quantitative scoring of synovitis in patients with rheumatoid arthritis (RA). METHODS: This prospective study included 38 RA patients (23 women and 15 men, mean age 51 years). All patients underwent low-field MRI of the hand before administration of contrast medium, after intravenous injection of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), and after another dose of 0.1 mmol/kg Gd-DTPA. Two readers (A and B) blinded to dosage independently scored the single dose and double dose image sets for synovitis according to outcome measures in rheumatology (OMERACT) recommendations. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were also calculated for each set. RESULTS: 149 metacarpophalangeal (MCP) joints were evaluated. There was good inter-reader agreement for each of the two sets (intra-class correlation coefficient of 0.75 for the single dose set and 0.83 for the double dose). Median CNR and SNR values were 5.4 and 15.9, respectively, for the single dose set and 8.5 and 16.6, respectively, for the double dose set (p<0.0001). Single dose set mean synovitis scores were 1.7 and 1.6 for readers A and B, respectively. Double dose set scores were 1.9 and 2.0, respectively. Thus, higher synovitis scores were recorded for the double dose sets than the single dose sets (p<0.005). CONCLUSION: In low-field MRI, when evaluating RA, the dose of the contrast material influences synovitis scoring. Therefore, dosage of contrast material should be taken into consideration when using extremity dedicated low-field MRI.
15748099 Efficacy, tolerability and cost effectiveness of disease-modifying antirheumatic drugs and 2005 Over the last decade, several new drugs have become available for the treatment of patients with rheumatoid arthritis. These agents include the new disease-modifying antirheumatic drug (DMARD) leflunomide and the biologic agents, tumor necrosis factor (TNF)-alpha antagonists and an interleukin (IL)-1 receptor antagonist. Methotrexate is commonly used as the first DMARD, has a well documented clinical efficacy and slows radiological deterioration. Sulfasalazine appears to have similar properties, albeit to a lesser extent. Leflunomide has similar efficacy as methotrexate but it is less tolerated than sulfasalazine. The adverse effect profiles of these three drugs makes regular laboratory monitoring mandatory. Several combination therapies with DMARDs were proven to be more effective than mono-DMARD therapy. However, until now these strategies have not been widely adopted. TNF antagonists are potent anti-inflammatory drugs, with a rapid onset of effects compared with traditional DMARDs. The IL-1 receptor antagonist, anakinra, has an intermediate place between methotrexate and the TNF antagonists with respect to efficacy. The adverse effects of TNF antagonists include an increased incidence of common and opportunistic infections. Thus far, anakinra has not been associated with an enhanced rate of opportunistic infections. Some of the biologic agents have been associated with worsening heart failure and demyelinating disease. The limited long-term safety data of the biologic agents are a point of concern because, at present, an enhanced risk for malignancies, particularly lymphoma, can not be excluded. Drug costs of traditional DMARDs are up to US dollars 3000 per year, whereas for the biologics the yearly drug costs range between US dollars 16,000 and > US dollars 20,000. Cost-effectiveness analyses are necessary to determine whether or not these high costs are justified. Unfortunately, adequate, prospective, economic evaluations are not yet available. Until these become available, treatment decisions will be based on the balance of direct costs and indirect costs and expected cost savings in the future.
16670289 CD64-directed immunotoxin inhibits arthritis in a novel CD64 transgenic rat model. 2006 May 15 Macrophages are known to play a key role during inflammation in rheumatoid arthritis (RA). Inflammatory macrophages have increased expression of CD64, the high-affinity receptor for IgG. Targeting this receptor through a CD64-directed immunotoxin, composed of an Ab against CD64 and Ricin A, results in effective killing of inflammatory macrophages. In this study, we show elevated levels of CD64 on synovial macrophages in both synovial lining and synovial fluid in RA patients. The CD64-directed immunotoxin efficiently eliminates activated synovial macrophages in vitro, while leaving quiescent, low CD64-expressing macrophages unaffected. To examine whether killing of CD64 macrophages results in therapeutic effects in vivo, we established an adjuvant arthritis (AA) model in newly generated human CD64 (hCD64) transgenic rats. We demonstrate that hCD64 regulation in this transgenic rat model is similar as in humans. After AA induction, treatment with CD64-directed immunotoxin results in significant inhibition of disease activity. There is a direct correlation between immunotoxin treatment and decreased macrophage numbers, followed by diminished inflammation and bone erosion in paws of these hCD64 transgenic rats. These data support synovial macrophages to play a crucial role in joint inflammation in AA in rats and in human RA. Selective elimination of inflammatory macrophages through a CD64-directed immunotoxin may provide a novel approach for treatment of RA.
15743489 Building the synovium: cadherin-11 mediates fibroblast-like synoviocyte cell-to-cell adhes 2005 Specific adhesion among like cells is a key determinant of the architecture of tissues. Homophilic (like binds like) adhesive interactions between cells are mediated by cadherins. These integral membrane glycoproteins have a crucial role in tissue morphogenesis during development and the maintenance of tissue integrity in adults. There is also an increasing recognition of a regulatory role for cadherins in a variety of cell functions, including cell migration. The recent identification of cadherin-11 expression in fibroblast-like synoviocytes (FLSs) has shed light on the mechanisms of synovial tissue organization and differentiation. Moreover, cadherin-11 expression in FLSs might also provide insight into pathways that determine the mesenchymal tissue response of the synovium to inflammation.
16622726 Enlarged psoas muscle and iliopsoas bursitis associated with a rapidly destructive hip in 2006 A 39-year-old man with rheumatoid arthritis developed femoral neuropathy secondary to iliopsoas bursitis. The adjacent hip joint was severely damaged. Magnetic resonance imaging showed enlargement and inflammation of the psoas muscle at the same side of iliopsoas bursitis. Iliopsoas bursitis and abnormal findings of the psoas muscle disappeared while the symptoms improved.
17038480 Mitogen activated protein kinase inhibitors: where are we now and where are we going? 2006 Nov Orally bioavailable compounds that target key intracellular signalling molecules are receiving increasing attention for the treatment of rheumatic diseases. The mitogen activated protein (MAP) kinases are especially attractive because they regulate both cytokine production and cytokine action. The MAP kinases are expressed and activated in rheumatoid arthritis (RA) synovium. Preclinical studies using MAP kinase inhibitors are very effective in animal models of arthritis, supporting their potential utility in human disease. Although the available data suggest a rationale for MAP kinase blockade, development of drugs has been hampered by toxicity and limited efficacy. Alternative strategies, such as targeting other kinases in the cascade or development of allosteric inhibitors have been proposed. These approaches might permit effective use of MAP kinase inhibitors for the treatment of rheumatic and immune-mediated diseases.
16465610 The role of macrophage migration inhibitory factor in the inflammatory immune response and 2006 Jan Rheumatoid arthritis (RA) is a debilitating disease of unknown etiology. Although the pathogenesis of RA is multifactorial, the contribution of cytokines is undoubtedly pivotal in the progression of the inflammatory process. One cytokine gaining recognition for its importance in inflammation is macrophage migration inhibitory factor (MIF). Initially described as a biological activity, a broad range of functions of MIF has emerged including induction of proinflammatory mediators as well as demonstrated roles in both innate and adaptive immunity. In RA, increased MIF levels have been demonstrated in serum, synovial fluid and tissue with the latter correlating with disease activity. In vitro, MIF induces production of key proinflammatory genes operative in arthritis, including IL-1, TNF, IL-6, IL-8, COX-2, PLA2, and MMPs. In addition, MIF regulates proliferation and apoptosis via direct effects on the tumor suppressor protein p53 implicating a role for MIF in synovial hyperplasia. In vivo, MIF antagonism or MIF deficiency result in decreased disease severity in animal models of RA further confirming a role for MIF in joint inflammation. Interestingly, MIF is induced by glucocorticoids and MIF in turn antagonises glucocorticoid effects. This unique relationship presents antagonism of MIF as a potentially effective steroid-sparing therapy.
15895881 Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis. 2005 Mar This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).
16633931 Subchondral insufficiency fracture of the femoral head after total knee arthroplasty in a 2006 We report an 80-year-old woman with rheumatoid arthritis (RA) who was found to have subchondral insufficiency fracture of the right femoral head after total knee arthroplasty (TKA). Initially, plain radiographs showed no obvious changes, but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low-intensity band on T1-weighted images of the right hip. She underwent hemiarthroplasty of the hip. This report describes a rare case of subchondral insufficiency fracture of the femoral head after TKA in a patient with RA.
17124249 Is shared care with annual hospital review better value for money than predominantly hospi 2007 May OBJECTIVE: To assess the cost effectiveness and cost effectiveness acceptability of symptom control delivered by shared care (SCSC) and aggressive treatment delivered in hospital (ATH) for established rheumatoid arthritis (RA). METHODS: Economic data were collected within the British Rheumatoid Outcome Study Group randomised controlled trial of SCSC and ATH. A broad perspective was used (UK National Health Service, social support services and patients). Cost per quality adjusted life year (QALY) gained, net benefit statistics and cost effectiveness acceptability curves were estimated. Costs and outcomes were discounted at 3.5%. Sensitivity analysis tested the robustness of the results to analytical assumptions. RESULTS: The mean (SD) cost per person was 4540 pounds (4700) in the SCSC group and 4440 pounds (4900) in the ATH group. The mean (SD) QALYs per person for 3 years were 1.67 (0.56) in the SCSC group and 1.60 (0.60) in the ATH group. If decision makers are prepared to pay > or = 2000 pounds to gain 1 QALY, SCSC is likely to be cost effective in 60-90% of cases. CONCLUSIONS: The primary economic analysis and sensitivity analyses indicate that SCSC is likely to be more cost effective than ATH in 60-90% of cases. This result seems to be robust to assumptions required by the analysis. This study is one of a limited number of randomised controlled trials to collect detailed resource use and health status data and estimate the costs and QALYs of treatment for established RA. This trial is one of the largest RA studies to use the EuroQol.
15647425 p53 expression in rheumatoid and psoriatic arthritis synovial tissue and association with 2005 Feb BACKGROUND: Overexpression and functional mutations of p53 have been found in the synovial tissue (ST) of patients with rheumatoid arthritis (RA), but their clinical significance remains unclear. OBJECTIVE: To analyse p53 expression in the ST of patients with RA and psoriatic arthritis (PsA) and its association with joint damage. METHODS: Synovial biopsy specimens were obtained by arthroscopy in 45 patients (27 RA, 18 PsA). Radiographs of hands, feet, and the joint undergoing arthroscopy were obtained to evaluate the presence of erosive disease. Synovial cell populations were analysed using CD4, CD8, CD138, CD20, and CD68 monoclonal antibodies (mAbs). The p53 protein was determined by immunohistology using DO7 mAb in 34 patients (18 RA, 16 PsA). In 11 patients with early RA, the association between p53 and 1 year progression of radiographic damage was analysed using the Larsen-Scott method. RESULTS: The p53 protein was detected in 16/18 (89%) patients with RA and in 9/16 (56%) patients with PsA, but its expression in RA was significantly higher than in PsA. In RA, p53 expression was significantly associated with erosive disease, and its scores were higher in patients with radiological progression. CD68 expression was also associated with erosions and radiological progression in RA. No association was found between either p53 or CD68 and erosive disease in PsA. CONCLUSIONS: These results suggest that p53 ST overexpression and association with joint damage is characteristic of RA rather than PsA, and that p53 ST expression might be a prognostic marker of joint damage in RA.
15641091 Evidence that anti-tumor necrosis factor therapy with both etanercept and infliximab induc 2005 Jan OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) antagonists is highly effective, but their mechanisms of action are not completely clear. Since anti-TNF therapy induces a decrease in synovial cellularity, this study focused on the modulation of RA synovial apoptosis following treatment with either soluble TNF receptor (etanercept) or TNF chimeric monoclonal antibody (infliximab). METHODS: Apoptosis (TUNEL and active caspase 3 staining) and cell surface markers were evaluated by immunohistochemistry in synovial biopsy samples obtained before and after 8 weeks of treatment with etanercept (12 patients) or infliximab (9 patients). We also determined by flow cytometry the in vitro effect of etanercept and infliximab on apoptosis of RA mononuclear cells derived from the synovial fluid (SF) and peripheral blood (PB). RESULTS: Eight weeks of treatment with etanercept and with infliximab significantly increased synovial apoptosis. This change was accompanied by a significant decrease in the synovial monocyte/macrophage population. The decrease in lymphocyte numbers did not reach statistical significance. In vitro, 24 hours of incubation with either etanercept or infliximab induced apoptosis of the SF monocyte/macrophage population. PB monocyte/macrophages were less susceptible to anti-TNF-mediated apoptosis. No changes in the rate of apoptosis were observed in the lymphocyte population derived from either SF or PB. CONCLUSION: In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population. This suggests a potential pathway that would account for the diminished synovial inflammation and the decreased numbers of synovial macrophages evident after TNF blockade.
15641102 Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis 2005 Jan OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.
16095122 Methotrexate use in rheumatoid arthritis is associated with few clinically significant liv 2005 Jul OBJECTIVE: To determine the frequency of liver function tests (LFT) abnormalities associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis (RA). METHODS: A retrospective chart review for demographic information, RA-specific history, medication history, complications of therapy, results of all available blood tests (specifically aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), albumin, creatinine), and liver biopsy reports was conducted for RA patients, who were currently using or have used MTX in the past. RESULTS: A total of 2791 LFTs were performed among 182 RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT evaluations demonstrated no abnormal results, compared with 30 patients (16.5%) who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients with at least one LFT abnormality (73.3%) continued treatment despite the elevation without further evaluation or change in therapy, and subsequent LFT assessments were within normal limits. 128 patients (70.3%) remained on MTX at the time of our study. The most common reason for discontinuation was inadequate response. CONCLUSIONS: MTX appears to be associated with very few clinically significant hepatic side effects. In view of these data, consideration as to revision of the current MTX monitoring guidelines in the direction of less frequent monitoring, especially in patients with no risk factors for liver disease, may be considered.
17158823 Reporting of radiographic methods in randomised controlled trials assessing structural out 2007 May BACKGROUND: Because an increasing number of clinical trials evaluating disease-modifying antirheumatic drugs in rheumatoid arthritis (RA) emphasise radiographic outcomes as a primary outcome, using a reproducible radiographic measure should be placed at a premium. AIM: To evaluate the reporting of radiographic methods in randomised trials assessing radiographic outcomes in RA. METHODS: Medline was searched for randomised controlled trials assessing radiographic outcomes published between January 1994 and December 2005 in general medical and specialty journals with a high impact factor. One reader extracted data (radiographic acquisition, assessment and reproducibility) using a standardised form. RESULTS: A total of 46 reports were included in the analysis. The mean (SD) methodological quality scores on the Jadad scale (range 0-5) and the Delphi list (0-9) were 2.9 (1.2) and 6.4 (1.3), respectively. Use of a standardised procedure for the acquisition of the radiographs was reported in 2 (4.3%) articles. 2 (4.3%) reports indicated that the quality of the radiographs was evaluated. In 65.2% of the reports, > or = 2 radiographic scores were used. Reporting of radiographic assessment was well detailed for number of readers (91.3%), information on readers (71.7%), blinding (91.4%) and how films were viewed (74.0%). The reproducibility of the reading was reported in 39.1% of the articles. CONCLUSION: The reporting of results of randomised controlled trials of radiographic outcomes in RA shows great variability in radiographic scores used. Reporting of radiographic methods could be improved upon, especially the acquisition procedure and the reproducibility of the reading.
16978905 Free radicals and antioxidants in normal physiological functions and human disease. 2007 Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
16730463 NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. 2006 Sep The family of nuclear factor-kappaB (NF-kappaB) transcription factors is intimately involved in the regulation of expression of numerous genes in the setting of the inflammatory response. Since inflammatory processes play a fundamental role in the damage of articular tissues, many in vitro and in vivo studies have examined the contribution of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases, in particular, of osteoarthritis (OA) and rheumatoid arthritis (RA). Inflammation, cartilage degradation, cell proliferation, angiogenesis and pannus formation are processes in which the role of NF-kappaB is prominent. Consequently, large efforts have been devoted to the study of the pharmacologic modulation of the NF-kappaB pathways. These studies have employed currently available therapeutic agents including non-steroidal anti-inflammatory drugs, corticosteroids, nutraceuticals and disease-modifying anti-rheumatic drugs, as well as novel small molecule inhibitors targeted to specific proteins of the NF-kappaB pathways. In addition, promising strategies such as improved antisense DNA therapy and RNA interference have been examined with encouraging results. However, since NF-kappaB also plays a crucial beneficial role in normal physiology and technical problems for effective gene therapy still remain, further research will be needed before NF-kappaB-aimed strategies become an effective therapy for joint diseases, such as OA and RA.
17067660 Toxoplasmic chorioretinitis and antitumor necrosis factor treatment in rheumatoid arthriti 2007 Feb OBJECTIVES: To present the data supporting the possible relationship of ocular toxoplasmosis to antitumor necrosis factor-alpha (TNF-alpha) therapy in patients with rheumatoid arthritis (RA). METHODS: A Medline search was performed using the words "toxoplasmosis, anti-TNF-alpha antagonists, chorioretinitis." We report 2 RA patients who developed ocular toxoplasmosis while receiving anti-TNF-alpha therapy. RESULTS: In addition to our patients with toxoplasmic chorioretinitis, there are 2 published cases of cerebral toxoplasmosis during treatment with anti-TNF-alpha agents. CONCLUSION: The risk of serious toxoplasmic infection during anti-TNF-alpha therapy for RA should be recognized.
17086383 The effects of sulfasalazine treatment on enthesal abnormalities of inflammatory rheumatic 2007 Jul The aim of this study was to evaluate the effects of a 1-year course of sulfasalazine monotherapy on enthesal abnormalities of inflammatory rheumatic diseases (IRDs) using ultrasonography. Thirty-six patients with IRD including 20 patients with rheumatoid arthritis (RA) and 16 patients with ankylosing spondylitis (AS) (22 women, 14 men, mean ages 43.3 +/- 8.8 years), and 18 healthy controls (10 women, 8 men, mean ages 42.5 +/- 9.9 years) matched by age and body mass index were enrolled in this study. For the evaluation of enthesal structures, all patients and controls underwent ultrasonographic (USG) examinations of five enthesal sites of both lower limbs using high-resolution and Doppler USG. An ultrasonographic score of lower limb enthesitis was calculated using Glasgow ultrasound enthesitis scoring system (GUESS). Clinical and laboratory activities of IRD patients were also evaluated. Patient group was made to undergo 2 g/day sulfasalazine monotherapy for 1 year. All evaluations were made at the beginning of the treatment and repeated after 1 year follow-up. Results showed that the frequency of enthesal abnormalities of the IRD group was significantly higher than controls. On USG examination, 301/1,296 (23.2%) enthesal structures were abnormal in IRD patients, and 19/648 (2.93%) structures were abnormal in controls. Mean GUESS score of the IRD group (6.40 +/- 2.41) was also significantly higher than controls (1.79 +/- 1.60) (p < 0.001). Although there was a significant improvement in clinical and laboratory activity parameters of the IRD patients, significant decrease was not observed in enthesal abnormalities (295/1,296 enthesal structures-22.7%) and mean GUESS score (6.20 +/- 2.38) after 1 year sulfasalazine trial. Additionally, there was no significant improvement in enthesal abnormalities and mean GUESS scores of AS and RA subgroups separately. Sulfasalazine treatment was not found effective on enthesal abnormalities of IRD patients. Further studies with larger groups including other IRDs are required to validate our results.
16216669 Analysis of vascular endothelial growth factor (VEGF) functional variants in rheumatoid ar 2005 Aug The vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic mediators related to inflammation-associated synovial angiogenesis. The aim of this study was to asses the role of -1154 G-->A (rs1570360) and -634 G-->C (rs2010963) VEGF gene functional variants with rheumatoid arthritis (RA). The population under study was composed of a total of 753 unrelated RA patients and 801 healthy controls. The VEGF -1154 G-->A and -634 G-->C polymorphism genotyping was performed by real-time polymerase chain reaction technology, using TaqMan 5' allelic discrimination assay. No evidence of association was observed between the -1154 G-->A and the -634 G-->C VEGF polymorphisms, or inferred VEGF haplotypes with RA susceptibility or clinical manifestations. Our results suggest that the analyzed VEGF promoter polymorphisms may not play a relevant role in RA pathogenesis in our population.