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The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.
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OBJECTIVE: Evaluate effectiveness/safety of tacrolimus in patients in Korea with active rheumatoid arthritis (RA) and unsuccessful response to disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Open-label, single-arm, non-comparative, 24-week, Phase-IV study in patients with active RA who had taken DMARDs for >6 months. Following a washout period, tacrolimus was initiated (baseline-12 weeks; dose 2 mg/day and 1.5 mg/day in patients aged ≤65 and >65 years, respectively). After 12 weeks, dose could be adjusted (remaining between 1~3 mg); treatment continued to 24 weeks. Primary endpoint was American College of Rheumatology 20% improvement (ACR20) (baseline-Week 24). Secondary endpoints included ACR50/ACR70 response, disease-activity score in 28 joints (DAS28) erythrocyte sedimentation rate (ESR), number of tender/swollen joints, and bone mineral density (BMD) loss. Adverse events (AEs) were recorded. RESULTS: Overall, 121 patients were analysed. Mean±standard deviation tacrolimus dose baseline-Week 24 was 1.81±0.47 mg/day. After 24 weeks, 64.5%, 39.7%, and 19.0% of patients were ACR20, ACR50, and ACR70 responders, respectively. DAS28-ESR score decreased from 5.5±0.8 (baseline) to 3.7±1.5 (Week 24; p < 0.0001); number of tender/swollen joints decreased. Between screening and Week 24, change in BMD-T score in lumbar and femur regions was −0.06±0.38 (p=0.1550) and −0.04±0.28 (p=0.0936), respectively, with no significant change in International Society for Clinical Densitometry classification. Fifty-six (46.3%) patients experienced 93 AEs; 75.3% were mild. No unexpected safety signals identified. CONCLUSION: Tacrolimus therapy was associated with a high proportion of ACR responders, and improved DAS28-ESR score and physical joint function during the study. Tacrolimus may be a suitable therapy for DMARD-resistant patients with RA.
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Humanos , Antirreumáticos , Artrite Reumatoide , Sedimentação Sanguínea , Densidade Óssea , Classificação , Densitometria , Fêmur , Articulações , Coreia (Geográfico) , Programas de Rastreamento , Osteoporose , Reumatologia , TacrolimoRESUMO
OBJECTIVES: The objectives of this study were to evaluate the long-term effect of anti-platelet treatment on the radiological progression of collagen-induced arthritis in rats. METHODS: Female Lewis rats with collagen-induced arthritis were divided into three experimental groups: saline, aspirin monotherapy (n = 12), and aspirin–clopidogrel dual therapy (n = 12). Drugs were administered daily and continued up to 70 days after the induction of arthritis. The clinical arthritis index (weight, morphology score, and paw thickness) and radiological scores were evaluated. RESULTS: The clinical arthritis index peaked on day 20, while the radiological scores peaked on day 35. No intergroup difference was observed in the clinical arthritis index throughout the experiment. The aspirin–clopidogrel dual therapy group had a significantly higher mean radiological score than the other groups (p = 0.045) on day 35. Further treatments resulted in significantly improved radiological findings in the aspirin monotherapy and aspirin–clopidogrel dual therapy groups on day 70 but no significant improvement in the saline group. CONCLUSION: Anti-platelet agent treatment improved radiological findings on day 70. These observations emphasize the importance of a future long-term study of the effects of anti-platelet agent treatment on arthritis.
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Animais , Feminino , Humanos , Ratos , Artrite , Artrite Experimental , AspirinaRESUMO
Behcet's disease (BD) is a multi-systemic inflammatory disease of unknown origin that affects nearly all organs including the nervous system. Although the neurological involvement is less frequent than other major presentations, it is important because it can produce severe disabilities. Peripheral nervous system manifestations are relatively rare in BD. Although few cases of peripheral neuropathy or myopathy have been reported in BD, they are cases of multiple neuropathies, sensorimotor peripheral neuropathy, or neuropathy autonomic dysfunction. Guillain-Barre syndrome (GBS), also known as an acute inflammatory demyelinating polyneuropathy, is an acute demyelinating polyradiculopathy of uncertain etiology. No case of GBS associated with BD in Korea has been reported. Herein we report on a patient of BD who suffered from weakness of extremities and was diagnosed as GBS.
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Humanos , Extremidades , Síndrome de Guillain-Barré , Coreia (Geográfico) , Doenças Musculares , Sistema Nervoso , Sistema Nervoso Periférico , Doenças do Sistema Nervoso Periférico , PolirradiculopatiaRESUMO
This article has been retracted.
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Systemic lupus erythematosus (SLE) is an autoimmune disorder affected by multiple genetic, hormonal and environmental factors, which makes it impossible to identify the exact cause of this ailment by only investigating SLE patients, who are genetically heterogeneous, and live in various environments. Therefore, the study of mouse models of lupus has provided valuable clues to help identify, and to validate, novel molecular pathways and targets implicated in the pathogenesis of the disease. While there is no perfect model to reflect all the disease phenotypes observed in human patients, disease subsets are represented in various animal models, which allows modulation of a particular pathophysiological pathway, resulting in the possibility of dissecting its specific contribution to disease development. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci, from which several candidate genes have been found, while induced models of lupus have provided insight into the role of environmental factors, as well as a better understanding of the cellular mechanisms by which SLE develops. Animal models also allow us to screen and evaluate potential preventive and therapeutic agents. Correlation of specific pathways in animal models to subsets of human disease offers the unique possibility of more accurate preclinical predictions of efficacy for single or combinatorial therapeutic approaches in the clinic. Here, we introduce various animal models of SLE, and review current data focused on genetic factors that are associated with susceptibility or phenotypes of lupus, leading into the present understanding of the genetic basis in lupus pathogenesis.
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Animais , Humanos , Camundongos , Lúpus Eritematoso Sistêmico , Modelos Animais , FenótipoRESUMO
Infliximab is a chimeric mouse/human monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha) that is used worldwide to treat rheumatic disease. However, the reactivation of tuberculosis, including extrapulmonary menifestation, is a severe side effect of anti-TNF-alpha treatment. Mycobacterium tubercluosis causes two forms of joint involvement, TB arthritis and Poncet's disease. Poncet's disease is a rare aseptic form of arthritis, known as reactive arthritis in tuberculosis. We encountered a case of tuberculous peritonitis with Poncet's disease in a 38-yearold man with a history of ankylosing spondylitis that was treated with infliximab. We report this case with a review of the literature.
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Humanos , Anticorpos Monoclonais , Artrite , Artrite Reativa , Articulações , Mycobacterium , Peritonite Tuberculosa , Doenças Reumáticas , Espondilite Anquilosante , Tuberculose , Fator de Necrose Tumoral alfa , InfliximabRESUMO
BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.
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Animais , Ratos , Complexo CD3 , Artrite , Artrite Experimental , Artrite Reumatoide , Biomarcadores , Colágeno Tipo II , Regulação para Baixo , Expressão Gênica , Genes Codificadores dos Receptores de Linfócitos T , Imunização , Articulações , Modelos Animais , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Antígenos de Linfócitos T , Membrana Sinovial , Linfócitos T , Timo , TranscriptomaRESUMO
BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3zeta, CD3delta, CD3epsilon, CD8alpha, and CD8beta genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.
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Animais , Ratos , Complexo CD3 , Artrite , Artrite Experimental , Artrite Reumatoide , Biomarcadores , Colágeno Tipo II , Regulação para Baixo , Expressão Gênica , Genes Codificadores dos Receptores de Linfócitos T , Imunização , Articulações , Modelos Animais , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Antígenos de Linfócitos T , Membrana Sinovial , Linfócitos T , Timo , TranscriptomaRESUMO
The forkhead-box J1 (FOXJ1) transcription factor could suppress a spontaneous activation of T cells and B cells through an induction of IkappaBbeta that results in repression of NF-kappaB activity. In Foxj1 deficiency mice, systemic autoimmune inflammation is quite common symptom. Therefore, deregulated Foxj1 is supposed to be associated with autoimmune diseases and/or other inflammatory diseases. Previously, we identified that polymorphisms of human FOXJ1 gene (g.-460C>T, g.1805G>T and g.3375G>C) are associated with allergic rhinitis in a Korean population. In present study, we compared the genotype and allele frequencies of these SNPs between healthy controls and systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) patients. We also investigated the relationships between each genotype and the expression levels of anti-nuclear antibodies in SLE patients, and rheumatoid factor and anti-cyclic citrullinated peptide in RA patients. The frequencies of haplotypes constructed by these FOXJ1 SNPs were compared between controls and SLE (or RA) patients. The results of genotype and allele analysis showed that the prevalence of polymorphism g.3375G>C was associated with the susceptibility of SLE (P = 0.0072 and 0.0042, respectively). But no significant association was found with RA. In the haplotype analysis, however, the main CGG showed a weak association between controls and RA patients (P = 0.048).
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide/complicações , Povo Asiático , Fatores de Transcrição Forkhead/genética , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Coreia (Geográfico) , Lúpus Eritematoso Sistêmico/complicações , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Leflunomide is a disease-modifying antirheumatic drug that has been available in Korea since 2003. Leflunomide induced interstitial pneumonitis has been reported as an adverse effect in other countries but not in Korea. A 57-year-old woman was treated with leflunomide since she had been resistant to methotrexate, hydroxychloroquine and sulfasalazine. She developed high fever, dyspnea, and non-productive cough 3 months after the administration of leflunomide. She was diagnosed leflunomide-induced interstitial pneumonitis based on history, physical, laboratory, radiologic and pathologic findings. The patient was treated by prednisolone 1 mg/kg/day with cholestyramine 24 g/day, resulting in dramatic improvement. Here we report a case of leflunomide induced pneumonitis treated successfully with high dose steroid.
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Feminino , Humanos , Pessoa de Meia-Idade , Artrite Reumatoide , Resina de Colestiramina , Tosse , Dispneia , Febre , Hidroxicloroquina , Coreia (Geográfico) , Doenças Pulmonares Intersticiais , Metotrexato , Pneumonia , Prednisolona , SulfassalazinaRESUMO
PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is characterized by a chronic T-cell response that has escaped normal control mechanisms. This review summarizes recent insights in pathways that are functional in RA and that favor continuous and pathogenic T-cell activation. RECENT FINDINGS: T-cell activation is ultimately determined by positive signals from costimulatory molecules and negative signals from regulatory T cells. Blockade of the classic costimulatory pathway, CD28-CD80 or CD86, is beneficial in RA. Additional pathways that predominantly control the activation of memory and effector T cells are functionally important in synovial inflammation. Some of these costimulatory molecules(such as stimulatory killer cell immunoglobulin-like receptors and NKG2D) appear to be relatively specific for RA and not to play a role in normal immune responses. In addition to this predominance of positive signals, age-disproportionate decline in thymic activity in RA may lead to a diminution of regulatory T cells and loss of their negative signals. SUMMARY: The successful treatment trial of RA with CTLA-4Ig clearly documents the importance of T-cell costimulation in RA disease activity. Novel costimulatory pathways may be of even greater significance than CD28 in RA and may represent promising new therapeutic targets. The finding of reduced thymic activity in RA is exciting and will stimulate further studies of T-cell homeostasis and the function of regulatory cells.
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Artrite Reumatoide , Autoimunidade , Homeostase , Inflamação , Linfócitos , Memória , Receptores KIR , Linfócitos T , Linfócitos T Reguladores , Nações UnidasRESUMO
In Behcet's disease, thrombocytopenia has rarely been reported in association with the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura or in association with cyclosporine or chlorambucil in the treatment of ocular inflammatory disease and meningoencephalitis. In this paper we report a case of thrombocytopenia in a 33-year-old female with Behcet's disease who has taken no medications for three years. After history taking, physical examination, routine laboratory and bone marrow examination, we diagnosed her case as idiopathic thrombocytopenic purpura (ITP). She recovered with high dose steroid treatment. To our knowledge, this is the first report having ITP in a patient with Behcet's disease.
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Adulto , Feminino , Humanos , Exame de Medula Óssea , Clorambucila , Ciclosporina , Síndrome Hemolítico-Urêmica , Meningoencefalite , Exame Físico , Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , TrombocitopeniaRESUMO
OBJECTIVE: To determine the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of knee osteoarthritis (OA). MEHTODS: In this randomized, placebo-controlled, double-blind trial, 51 patients with knee OA, diagnosed according to the criteria of the American College of Rheumatology, were treated with PEMF or placebo. Eleven patients failed to attend after screening and were excluded from analysis. Treatment consisted of 3 half-hour periods of exposure per week over 6 weeks in a specially designed cylindrical device that emits low-frequency pulsed electromagnetic fields (25 gauss, 12 Hz). The primary outcome measure was reduction in pain on movement using a 10 cm visual analog scale. Secondary outcome measures included joint swelling and tenderness, the Lequesne index, and overall evaluations of improvement by the patient and examining physician. Evaluations were made at baseline, 3 week and 6 week during treatment and 4 weeks after finishing treatment. RESULTS: There were no significant differences between PEMF and placebo groups in respect of any outcome measures after treatment. Range of motion and knee swelling tended to be improved in the PEMF group. There were no clinically relevant adverse effects attributable to PEMF treatment. CONCLUSION: These results suggest that the PEMF treatment has no clinically significant benefits in patients with knee OA resistant to conventional treatment. The larger studies are needed to confirm the efficacy of PEMF therapy in knee OA.
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Humanos , Campos Eletromagnéticos , Articulações , Joelho , Imãs , Programas de Rastreamento , Osteoartrite do Joelho , Avaliação de Resultados em Cuidados de Saúde , Amplitude de Movimento Articular , Reumatologia , Escala Visual AnalógicaRESUMO
Remitting seronegative symmetric synovitis with pitting edema (RS3 PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3 PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.
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Adulto , Feminino , Humanos , Anticorpos Antinucleares/biossíntese , Artrite/complicações , Biópsia , Sedimentação Sanguínea , Diagnóstico Diferencial , Edema/diagnóstico , Linfócitos/patologia , Prednisolona/uso terapêutico , Fator Reumatoide/biossíntese , Glândulas Salivares/patologia , Síndrome de Sjogren/diagnóstico , Síndrome , Sinovite/diagnósticoRESUMO
BACKGROUNDS: Rheumatoid factor (RF) is common serological marker for the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new antifilaggrin antibody test by enzyme linked immunosorbent assay (ELISA) in RA. METHODS: Recombinant human filaggrin was deiminated in vitro by peptidylarginine deiminase and used as the coating antigen for ELISA. We performed the RF and the antifilaggrin antibody for 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals and evaluated the sensitivities and specificities of RF and antifilaggrin antibody. Optimal cut off values were calculated as mean+2SD in 95% confidence interval except 3SD for 286 normal individuals. Optimal cut off values of antifilaggrin antibody and RF were 9.6 U/ml and 12 U/ml, respectively. RESULTS: The sensitivities and specificities of antifilaggrin antibody were 44.8% and 89.2% at optimal cut off values. The sensitivity and specificity of RF were 75.0% and 83.3%. Combination of "antifilaggrin antibody and RF" showed significantly high specificity of 95.2% and that of "antifilaggrin antibody or RF" showed slightly high sensitivity of 79.3% at optimal cut off values. Antifilaggrin antibody was positive in 17.3% among 81 sero-negative RA patients. CONCLUSION: We considered that antifilaggrin antibody could be used a supplementary test of RF for the diagnosis of RA, because "antifilaggrin antibody and RF" had higher diagnostic specificity than RF alone and antifilaggrin antibody test was easy, convenient ELISA method in performance.
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Humanos , Artrite Reumatoide , Diagnóstico , Ensaio de Imunoadsorção Enzimática , Fator Reumatoide , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The Rheumatoid Factor (RF) is the only serological marker in the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new anti-cyclic citrullinated peptide antibodies test (anti-CCP) by the enzyme-linked immunosorbent assay (ELISA) in RA. METHODS: A cyclic peptide variant that contains citrulline was used as an antigenic substrate in ELISA. We performed the RF and anti-CCP in 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals. Diagnostic performances such as sensitivity and specificity were evaluated by the receiver-operator characteristics (ROC) curve at optimal cut-off values. The optimal cut-off values were determined at the maximal point of the area under the curve. RESULTS: The sensitivity and specificity of anti-CCP were 72.8% and 92% at 3.8 U/mL. The sensitivity and specificity of RF were 80.6% and 78.5% at 9 U/mL. The sensitivity and specificity of anti-CCP and RF were 67%, 95.2% and 63.3%, 90% at 8.4 U/mL, 20 U/mL, respectively. A combination of anti-CCP with RF increased the sensitivity and specificity to 79.3%, 96.4%, respectively. Anti-CCP was positive in 23.8% among 63 sero-negative RA patients. CONCLUSIONS: We considered that the anti-CCP might be useful as another new serological marker for the diagnosis of a RA combination with RF, or not, because the anti-CCP has a higher diagnostic specificity than the RF and was an easy, convenient ELISA method in performance.
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Humanos , Anticorpos , Artrite Reumatoide , Citrulina , Diagnóstico , Ensaio de Imunoadsorção Enzimática , Fator Reumatoide , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: A number of soluble factors,which play important role in the pathophysiology of rheumatoid synovitis are also known to be involved in osteoclast differentiation and activation through RANKL (Receptor activator of NF-kB ligand). To investigate the importance of RANKL in the pathogenesis of bone erosion in rheumatoid arthritis (RA) patients, we analyzed the expression of RANKL and Osteoprotegerin (OPG) and examined the formation of osteoclasts in rheumatoid synovial fibroblasts under the influence of various osteotropic factors. METHODS: Primary culture synoviocytes or fibroblast-like synoviocytes isolated from synovial tissues of 8 RA patients were cultured and treated with IL-1beta (2 ng/ml), TNF-alpha (2 ng/ml), INF-gamma(1000 micro/ml), IL-15 (10 ng/ml), IL-12 (10 ng/ml), dexamethasone (10(-9) M), PMA (10 ng/ml) or 1,25 (OH)2D3 (10(-9) M) for 18 hours. Expression RANKL or OPG mRNA was measured by semiquantitative RT-PCR within linear amplification condition. TRAP (+) MNC (tartrate resistant acid phosphatase-positive multinucleated cell) formation was induced from primary culture synoviocytes or in coculture system of synovial fibroblasts with PBMCs in the presence of M-CSF and 1,25 (OH)2D3. RESULTS: 1. The intensity of base-line expression was different from patient to patient. Primary culture synoviocytes and synovial fibroblasts express RANKL and OPG mRNA with decreasing intensity when they are passaged. 2. Expresssion of RANKL mRNA was significantly increased by 1,25 (OH)2D3 and IL-1beta (158.8+/-21% and 197.2+/-17% of controls, p<0.05 and p<0.005, respectively), while decreased significantly by dexamethasone (25.6+/-4.6% of controls, p<0.005). Expression of RANKL mRNA was significantly increased by IL-1beta and decreased by dexamethasone, in a dose- and time-dependant manner. 3. TRAP (+) MNCs are formed from primary culture synoviocytes or in coculture system of synovial fibroblasts and PBMC in the presence of M-CSF and 1,25 (OH)2D3. Dexamethasone clearly inhibited TRAP (+) MNCs formation from synovial cells. CONCLUSION: The regulatory mechanism for the expression of RANKL or OPG in rheumatoid synoviocytes might be different from that in bone marrow cells. Modulating the expression of these molecules could have potential therapeutic implication targeting bone destruction in RA.
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Humanos , Artrite Reumatoide , Células da Medula Óssea , Técnicas de Cocultura , Dexametasona , Fibroblastos , Interleucina-12 , Interleucina-15 , Fator Estimulador de Colônias de Macrófagos , NF-kappa B , Osteoclastos , Osteoprotegerina , RNA Mensageiro , Sinovite , Fator de Necrose Tumoral alfaRESUMO
The appendiceal mucocele is a rare disorder, usually found incidentally during ultrasonography or radiologic studies. Mucoceles of the appendix include benign or malignant disease. Both of benign cystadenoma and malignant cystadenocarcinoma are characterized by an obstructed, mucin-filled appendix displacing the cecum. We experienced a case of partial obstruction of large bowel who had a cystadenoma at appendix and a colon cancer at other site on operation field. Here in, we report a case of appendiceal mucocele and concominant colon cancer with the review of literatures.