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1.
Ann Rheum Dis ; 78(11): 1576-1582, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31391176

RESUMO

OBJECTIVES: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

2.
J Endocrinol ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508414

RESUMO

Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry. TLR9 expression was inhibited using specific siRNA mediated knock-down, and TLR9 signaling was induced using specific class A, B and C agonistic CpG-oligodeoxynucleotide (ODN)-treatment versus ODN controls in 3T3-L1 adipocytes and in primary murine adipocytes from TLR9wt/wt- versus TLR9-/--mice. We found that TLR9 gene expression is induced during AD, and that TLR9 protein is expressed in murine gonadal and human visceral adipocytes. AD depends on intact TLR9 expression. TLR9-/- mice demonstrate significantly reduced adiponectin serum levels, while siRNA-mediated TLR9 knock-down led to reduced adiponectin mRNA expression in adipocytes. TLR9 ligands (CpG-ODNs) inhibit pro-inflammatory resistin secretion in mature 3T3-L1 adipocytes. TLR9-/- as compared to TLR9wt/wt adipocytes exhibit increased resistin and MCP1 secretion and reduced adiponectin secretion into cell culture supernatants, while TLR9 ligands (ODNs) show differential effects in TLR9-/- versus TLR9wt/wt primary murine adipocytes. TLR9 expression is significantly increased in visceral compared to subcutaneous adipose tissue depots in non-diabetic obese patients and correlates with systemic resistin levels in a compartment-specific manner. Thus, adipocytic TLR9 is a putative, new protective factor during (obesity-associated) adipose tissue inflammation.

3.
RMD Open ; 4(Suppl 1): e000782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402270

RESUMO

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

4.
Ann Rheum Dis ; 77(12): 1705-1709, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30194273

RESUMO

OBJECTIVES: Patients with difficult-to-treat rheumatoid arthritis (RA) remain symptomatic despite treatment according to current European League Against Rheumatism (EULAR) management recommendations. These focus on early phases of the disease and pharmacological management. We aimed to identify characteristics of difficult-to-treat RA and issues to be addressed in its workup and management that are not covered by current management recommendations. METHODS: An international survey was conducted among rheumatologists with multiple-choice questions on disease characteristics of difficult-to-treat RA. Using open questions, additional items to be addressed and items missing in current management recommendations were identified. RESULTS: 410 respondents completed the survey: 50% selected disease activity score assessing 28 joints >3.2 OR presence of signs suggestive of active disease as characteristics of difficult-to-treat RA; 42% selected fatigue; 48% selected failure to ≥2 conventional synthetic disease-modifying antirheumatic drugs (DMARDs) AND ≥2 biological/targeted synthetic DMARDs; 89% selected inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering comorbidities, extra-articular manifestations and polypharmacy were identified as important issues missing in current management recommendations. CONCLUSIONS: There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations.

5.
Ann Rheum Dis ; 77(11): 1619-1626, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29980577

RESUMO

Tetraspanins function as membrane adaptors altering cell-cell fusion, antigen presentation, receptor-mediated signal transduction and cell motility via interaction with membrane proteins including other tetraspanins and adhesion molecules such as integrins. CD82 is expressed in several malignant cells and well described as tumour metastasis suppressor. Rheumatoid arthritis (RA) is based on persistent synovial inflammation and joint destruction driven to a large extent by transformed-appearing activated synovial fibroblasts (SF) with an increased migratory potential. OBJECTIVE: CD82 is upregulated in RA synovial fibroblasts (RASF) compared with osteoarthritis (OA) SF as well as within RA compared with OA synovial lining layer (LL) and the role of CD82 in RASF was evaluated. METHODS: CD82 and integrin immunofluorescence was performed. Lentiviral CD82 overexpression and siRNA-mediated knockdown was confirmed (realtime-PCR, Western blot, immunocytochemistry). RASF migration (Boyden chamber, scrape assay), attachment towards plastic/Matrigel, RASF-binding to endothelial cells (EC) and CD82 expression during long-term invasion in the SCID-mouse-model were evaluated. RESULTS: CD82 was induced by proinflammatory stimuli in SF. In RA-synovium, CD82 was expressed in RASF close to blood vessels, LL, sites of cartilage invasion and colocalised with distinct integrins involved in tumour metastasis suppression but also in RA-synovium by RASF. CD82 overexpression led to reduced RASF migration, cell-matrix and RASF-EC adhesion. Reduced CD82 expression (observed in the sublining) increased RASF migration and matrix adhesion whereas RASF-EC-interaction was reduced. In SCID mice, the presence of CD82 on cartilage-invading RASF was confirmed. CONCLUSION: CD82 could contribute to RASF migration to sites of inflammation and tissue damage, where CD82 keeps aggressive RASF on site.

6.
Arthritis Res Ther ; 20(1): 17, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382380

RESUMO

BACKGROUND: Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung function during and after therapy are scarce. METHODS: We analysed patients fulfilling American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2013 criteria for SSc-ILD and at least one report of IS. Types of IS, pulmonary function tests (PFT) and PFT courses during IS treatment were evaluated. RESULTS: EUSTAR contains 3778/11,496 patients with SSc-ILD (33%), with IS in 2681/3,778 (71%). Glucocorticoid (GC) monotherapy was prescribed in 30.6% patients with GC combinations plus cyclophosphamide (CYC) (11.9%), azathioprine (AZA) (9.2%), methotrexate (MTX) (8.7%), or mycophenolate mofetil (MMF) (7.3%). Intensive IS (MMF + GC, CYC or CYC + GC) was started in patients with the worst PFTs and ground glass opacifications on imaging. Patients without IS showed slightly less worsening in forced vital capacity (FVC) when starting with FVC 50-75% or >75%. GC showed negative trends when starting with FVC <50%. Regarding diffusing capacity for carbon monoxide (DLCO), negative DLCO trends were found in patients with MMF. CONCLUSIONS: IS is broadly prescribed in SSc-ILD. Clusters of clinical and functional characteristics guide individualised treatment. Data favour distinguished decision-making, pointing to either watchful waiting and close monitoring in the early stages or start of immunosuppressive treatment in moderately impaired lung function. Advantages of specific IS are difficult to depict due to confounding by indication. Data do not support liberal use of GC in SSc-ILD.

7.
Ann Rheum Dis ; 77(7): 1032-1038, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29463517

RESUMO

OBJECTIVES: The aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc). METHODS: This was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward-backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence. RESULTS: The adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale. CONCLUSION: The individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment.

9.
J Rheumatol ; 43(1): 66-74, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26568599

RESUMO

OBJECTIVE: Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. METHODS: The data of 3248 patients with SSc were analyzed. RESULTS: Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. CONCLUSION: These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.


Assuntos
Qualidade de Vida , Sistema de Registros , Escleroderma Sistêmico/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Vasodilatadores/uso terapêutico , Adulto , Fatores Etários , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento , Doenças Vasculares/diagnóstico , Doenças Vasculares/epidemiologia , Vasodilatadores/farmacologia , Adulto Jovem
10.
Ann Rheum Dis ; 75(4): 681-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25688073

RESUMO

OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. METHODS: Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. RESULTS: 3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure): 3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). CONCLUSIONS: In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Dedos , Dermatoses da Mão/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Úlcera Cutânea/fisiopatologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Dermatoses da Mão/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Nefropatias/etiologia , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/mortalidade , Úlcera Cutânea/etiologia , Volume Sistólico , Capacidade Vital
11.
Ann Rheum Dis ; 74(4): 730-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24389298

RESUMO

BACKGROUND: Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. OBJECTIVES: To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). METHODS: The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. RESULTS: Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. CONCLUSIONS: These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.


Assuntos
Doenças do Tecido Conjuntivo/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Autoanticorpos/imunologia , Cardiomiopatias/etiologia , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/imunologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Gastroenteropatias/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fibrose Pulmonar/etiologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Síndrome
12.
J Clin Epidemiol ; 67(6): 706-14, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24721558

RESUMO

OBJECTIVES: Classification criteria for systemic sclerosis (SSc) are being developed. The objectives were to develop an instrument for collating case data and evaluate its sensibility; use forced-choice methods to reduce and weight criteria; and explore agreement among experts on the probability that cases were classified as SSc. STUDY DESIGN AND SETTING: A standardized instrument was tested for sensibility. The instrument was applied to 20 cases covering a range of probabilities that each had SSc. Experts rank ordered cases from highest to lowest probability; reduced and weighted the criteria using forced-choice methods; and reranked the cases. Consistency in rankings was evaluated using intraclass correlation coefficients (ICCs). RESULTS: Experts endorsed clarity (83%), comprehensibility (100%), face and content validity (100%). Criteria were weighted (points): finger skin thickening (14-22), fingertip lesions (9-21), friction rubs (21), finger flexion contractures (16), pulmonary fibrosis (14), SSc-related antibodies (15), Raynaud phenomenon (13), calcinosis (12), pulmonary hypertension (11), renal crisis (11), telangiectasia (10), abnormal nailfold capillaries (10), esophageal dilation (7), and puffy fingers (5). The ICC across experts was 0.73 [95% confidence interval (CI): 0.58, 0.86] and improved to 0.80 (95% CI: 0.68, 0.90). CONCLUSIONS: Using a sensible instrument and forced-choice methods, the number of criteria were reduced by 39% (range, 23-14) and weighted. Our methods reflect the rigors of measurement science and serve as a template for developing classification criteria.


Assuntos
Pesquisa Biomédica/instrumentação , Técnicas de Apoio para a Decisão , Escleroderma Sistêmico/classificação , Consenso , Estudos de Viabilidade , Humanos , Reprodutibilidade dos Testes , Escleroderma Sistêmico/diagnóstico
13.
Ann Rheum Dis ; 73(4): 771-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23632195

RESUMO

OBJECTIVE: To test whether the tyrosine kinase Tyro3 affects arthritis. Tyro3, the ligand of growth arrest-specific protein 6 (GAS6) is a receptor tyrosine kinase involved in cell survival. Tyro3 and GAS6 are expressed in the arthritic synovium, and in vitro studies have shown their role in osteoclast differentiation. METHODS: Bone was assessed by micro CT and histomorphometry in Tyro3-deficient (Tyro3(-/-)) and wild-type mice. Arthritis was induced in both genotypes, and Gas6 level was measured by ELISA. Synovitis, synovial hyperplasia, bone erosion, osteoclast activation and osteoclast gene expression were assessed by histomorphometry and reverse transcriptase-PCR, respectively. In vitro osteoclast differentiation assays were performed in Tyro3(-/-) and wild-type mice. Furthermore, effects of Tyro3 and GAS6 on human synovial fibroblast proliferation and osteoclastogenesis were assessed in human cells. RESULTS: Tyro3(-/-) mice had significantly higher bone mass than wild-type littermates. Induction of arthritis increased GAS6 serum levels. Arthritic Tyro3(-/-) mice showed less synovial hyperplasia, osteoclast numbers and bone damage compared with controls. In vivo expression of osteoclast-associated receptor and receptor activator of nuclear factor-κB and in vitro osteoclastogenesis were impaired in Tyro3(-/-) mice. GAS6 also induced synovial fibroblast proliferation and osteoclast differentiation in human cells in Tyro3-dependent manner. CONCLUSIONS: These findings indicate that Tyro3 is a critical signal for synovial hyperplasia, osteoclast differentiation and bone erosion during arthritis. GAS6 and Tyro3 therefore constitute therapeutic targets to inhibit synovial hyperplasia and associated bone erosion.


Assuntos
Artrite Experimental/complicações , Artrite Reumatoide/complicações , Osteoporose/prevenção & controle , Receptores Proteína Tirosina Quinases/fisiologia , Membrana Sinovial/patologia , Animais , Artrite Experimental/enzimologia , Artrite Experimental/metabolismo , Artrite Reumatoide/enzimologia , Artrite Reumatoide/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Técnicas de Inativação de Genes , Humanos , Hiperplasia/etiologia , Hiperplasia/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Osteoporose/enzimologia , Osteoporose/etiologia , Receptores Proteína Tirosina Quinases/deficiência , Receptores Proteína Tirosina Quinases/genética , Transdução de Sinais/fisiologia , Membrana Sinovial/metabolismo
14.
Biologics ; 6: 191-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22848150

RESUMO

PURPOSE: To assess the efficacy of one course of rituximab (two 1-g doses) compared to an alternative tumor necrosis factor-α (TNFα) blocker in rheumatoid arthritis patients who had experienced one previous TNFα blocker failure (eg, etanercept, adalimumab, or infliximab). PATIENTS AND METHODS: The efficacy of both treatments was studied in this retrospective, multicenter, noninterventional cohort study with 196 patients. All patients had active rheumatoid arthritis defined by a Disease Activity Score-28 of ≥3.2 despite having TNFα blocker therapy, and were followed over 6.6 months on average after switching to rituximab versus a second TNFα blocker (ie, switching to etanercept, adalimumab, or infliximab) at baseline. RESULTS: At baseline, both cohorts showed similar demographic and disease-related characteristics (including Disease Activity Score-28). At the end of observation, mean Disease Activity Score-28 was significantly lower after treatment with rituximab than with a second TNFα blocker (-1.64 [95% confidence interval: -1.92; -1.36] versus -1.19 [95% confidence interval: -1.42; -0.96], P = 0.013). This difference between the two groups was even more pronounced when patients were seropositive for rheumatoid factor (-1.66 versus -1.17, P = 0.018) and anti-cyclic citrullinated peptide antibodies (-1.75 versus -1.06, P = 0.002). More rituximab-treated patients achieved good European League Against Rheumatism response than TNFα blocker-treated patients (30% versus 15%), and less patients were nonresponders (22% versus 35%) according to European League Against Rheumatism criteria (P = 0.022, chi-squared test). CONCLUSION: Treatment with rituximab was more effective than a second TNFα blocker therapy in rheumatoid arthritis patients after failure of the first TNFα blocker. It was found that anti-cyclic citrullinated peptide antibodies may be a useful predictive biomarker for response to rituximab in patients with TNFα blocker treatment failure.

15.
Arthritis Care Res (Hoboken) ; 64(3): 351-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22052558

RESUMO

OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated. Our objective was to select a set of items potentially useful for the classification of SSc using consensus procedures, including the Delphi and nominal group techniques (NGT). METHODS: Items were identified through 2 independent consensus exercises performed by the Scleroderma Clinical Trials Consortium and the European League Against Rheumatism Scleroderma Trials and Research Group. The first-round items from both exercises were collated and redundancies were removed, leaving 168 items. A 3-round Delphi exercise was performed using a 1-9 scale (where 1 = completely inappropriate and 9 = completely appropriate) and a consensus meeting using NGT was conducted. During the last Delphi round, the items were ranked on a 1-10 scale. RESULTS: In round 1, 106 experts rated the 168 items. Those with a median score of <4 were removed, resulting in a list of 102 items. In round 2, the items were again rated for appropriateness and subjected to a consensus meeting using NGT by European and North American SSc experts (n = 16), resulting in 23 items. In round 3, SSc experts (n = 26) then individually scored each of the 23 items in a last Delphi round using an appropriateness score (1-9) and ranking their 10 most appropriate items for the classification of SSc. Presence of skin thickening, SSc-specific autoantibodies, abnormal nailfold capillary pattern, and Raynaud's phenomenon ranked highest in the final list that also included items indicating internal organ involvement. CONCLUSION: The Delphi exercise and NGT resulted in a set of 23 items for the classification of SSc that will be assessed for their discriminative properties in a prospective study.


Assuntos
Escleroderma Sistêmico/classificação , Consenso , Técnica Delfos , Feminino , Humanos , Escleroderma Sistêmico/diagnóstico
16.
Ann N Y Acad Sci ; 1193: 167-75, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20398025

RESUMO

This study was performed to evaluate whether specific patterns of cerebral lesions can be identified in different rheumatic disease entities. In 132 patients with different connective tissue diseases and vasculitides (systemic lupus erythematosus [SLE], systemic sclerosis [SSc], mixed connective tissue disease [MCTD], Wegener's granulomatosis [WG], immunocomplex vasculitides, antiphospholipid antibody syndrome [APS]), cerebral magnetic resonance imaging scans were performed. Patients were examined clinically, and laboratory parameters including autoantibodies were determined. Distinct distibution patterns could be identified; in WG, most lesions were seen in the cortex, the periventricular region, basal ganglia, and pons. In both SSc and MCTD, highest numbers of lesions could be detected in the corticomedullary junction. In APS, basal ganglia and periventricular white matter were involved predominantly. Generally, the maximum score of cerebral lesions correlated significantly with patients' age. Pathological values for antinuclear antibodies and increased levels of antiphospholipid antibodies were significantly correlated with the presence of cerebral lesions. WG patients and patients with other vasculitides most frequently showed neurological abnormalities. This study in patients with different rheumatic diseases showed distinct distribution patterns of cerebral lesions, which might help to differentiate between them.


Assuntos
Cérebro/patologia , Doenças do Tecido Conjuntivo/imunologia , Vasculite Sistêmica/imunologia , Adulto , Síndrome Antifosfolipídica/imunologia , Cérebro/diagnóstico por imagem , Feminino , Seguimentos , Granulomatose com Poliangiite/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia
17.
Mod Rheumatol ; 20(3): 311-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20169391

RESUMO

We report on a 33-year-old female patient with a relatively mild clinical case of TNF-receptor associated periodic syndrome (TRAPS) and her 58-year-old father in whom end-stage renal disease due to TRAPS-related AA-amyloidosis has already developed. TRAPS was caused by a I170N mutation that has previously not been associated with amyloidosis. It remains unclear if an only mildly affected patient such as ours would benefit from treatment considering her father's severe course of disease. The relevant literature on this problem is reviewed.


Assuntos
Doenças Hereditárias Autoinflamatórias/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adulto , Amiloidose/genética , Amiloidose/imunologia , Feminino , Doenças Hereditárias Autoinflamatórias/imunologia , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/imunologia , Mutação , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia
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