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1.
Public Health ; 232: 86-92, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759472

RESUMO

OBJECTIVES: Lung cancer remains a significant global public health challenge and is still one of the leading causes of cancer-related death in Argentina. This study aims to assess the disease and economic burden of lung cancer in the country. STUDY DESIGN: Burden of disease study. METHODS: A mathematical model was developed to estimate the disease burden and direct medical cost attributable to lung cancer. Epidemiological parameters were obtained from local statistics, the Global Cancer Observatory, the Global Burden of Disease databases, and a literature review. Direct medical costs were estimated through micro-costing. Costs were expressed in US dollars (US$), April 2023 (1 US$ = 216.38 Argentine pesos). A second-order Monte Carlo simulation was performed to estimate the uncertainty. RESULTS: Considering approximately 10,000 deaths, 12,000 incident cases, and 14,000 5-year prevalent cases, the economic burden of lung cancer in Argentina in 2023 was estimated to be US$ 556.20 million (396.96-718.20), approximately 1.4% of the total healthcare expenditure for the country. The cost increased with a higher stage of the disease, and the main driver was drug acquisition (80%). A total of 179,046 disability-adjusted life years could be attributable to lung cancer, representing 10% of the total cancer. CONCLUSION: The disease and economic burden of lung cancer in Argentina implies a high cost for the health system and would represent 19% of the previously estimated economic burden for 29 cancers in Argentina.


Assuntos
Efeitos Psicossociais da Doença , Neoplasias Pulmonares , Humanos , Argentina/epidemiologia , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Custos de Cuidados de Saúde/estatística & dados numéricos , Modelos Teóricos , Adulto , Anos de Vida Ajustados por Deficiência , Idoso de 80 Anos ou mais , Gastos em Saúde/estatística & dados numéricos
2.
Scand J Rheumatol ; 48(1): 17-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30260261

RESUMO

OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Sistema de Registros , Fator Reumatoide/sangue , Rituximab/uso terapêutico , Fumar/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/epidemiologia , Biomarcadores/sangue , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Fumar/epidemiologia
3.
Clin Exp Immunol ; 184(2): 159-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26701127

RESUMO

Interleukin (IL)-36α, IL-36ß and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36ß and IL-38 mRNA, was induced and correlated with IL-1ß and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, ß, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1ß, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1ß and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68⁺ macrophages, dendritic/Langerhans cells and CD79α⁺ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36ß and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.


Assuntos
Artrite Reumatoide/patologia , Doença de Crohn/patologia , Interleucina-1/biossíntese , Interleucinas/biossíntese , Psoríase/patologia , Aminoquinolinas , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/imunologia , Células CACO-2 , Linhagem Celular , Doença de Crohn/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Imiquimode , Inflamação/imunologia , Inflamação/patologia , Interleucina-1/genética , Interleucinas/genética , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Queratinócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Plasmócitos/metabolismo , Psoríase/imunologia , RNA Mensageiro/biossíntese , Pele/metabolismo , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo , Células Th17/imunologia
4.
Rev Med Suisse ; 10(421): 603-6, 608, 2014 Mar 12.
Artigo em Francês | MEDLINE | ID: mdl-24701713

RESUMO

Since the 50s oral glucocorticoids including prednisone are used in the management of rheumatoid arthritis due to their efficacy and the limited availability of the other treatments in the past. Thereafter numerous studies confirmed the usefulness of prednisone in controlling clinical inflammatory manifestations and the progression of radiographic damage. Sixty years later the position of prednisone in the treatment strategy of rheumatoid arthritis is still controversial, considering the presence of numerous side effects and the availability of other effective treatments. If prednisone can be reasonably used in some situations either as bridging therapy in combination with other treatments or in case of flare, its long-term use should be avoided.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Doenças Cardiovasculares/etiologia , Humanos , Infecções/etiologia , Osteoporose/etiologia
5.
Rev Med Suisse ; 10(421): 595-6, 598, 600-2, 2014 Mar 12.
Artigo em Francês | MEDLINE | ID: mdl-24701712

RESUMO

The natural history of rheumatoid arthritis, previously burdened with high morbidity, has been strongly modified by appropriate treatment. Early diagnosis and treatment, and follow-up by a specialist, with the aim to achieve remission or low disease activity, are essential for the functional outcome of patients. Disease-modifying anti-rheumatic drugs include "conventional" treatments like methotrexate, biologic therapies such as TNF-inhibitors, abatacept, tocilizumab and rituximab, and targeted synthetic therapies such as tofacitinib (a JAK kinase inhibitor). New treatments currently under study should allow rheumatologists to successfully treat even more patients than nowadays.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/farmacologia , Artrite Reumatoide/classificação , Humanos
6.
Rev Med Suisse ; 10(421): 609-10, 612, 614-5, 2014 Mar 12.
Artigo em Francês | MEDLINE | ID: mdl-24701714

RESUMO

Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumour is an articular pathology that occurs predominantly in young adults and is caused by an abnormal proliferation of the synovial membrane. The clinical presentation includes pain and joint swelling. MRI represents the best imaging modality to investigate this disease but the histopathology of synovial tissue provides the definitive diagnosis. The management of PVNS is often difficult due to the high risk of relapse after treatment. The objective of this article is to review the literature regarding the diagnosis and therapy of this poorly understood condition.


Assuntos
Sinovite Pigmentada Vilonodular/diagnóstico , Sinovite Pigmentada Vilonodular/terapia , Diagnóstico por Imagem , Humanos , Joelho/patologia , Sinovite Pigmentada Vilonodular/epidemiologia
7.
Rev Med Suisse ; 9(377): 569-70, 572, 574-5, 2013 Mar 13.
Artigo em Francês | MEDLINE | ID: mdl-23534244

RESUMO

Erosive hand osteoarthritis is common and debilitating. Diagnosis is based on the presence of bone erosions which can appear late. Ultrasonography allows earlier diagnosis. The presence of apatite deposits could be of poor prognosis. Non pharmacological treatment includes the explanation of the inflammatory phenomena involved and the use of splints and physical therapy. Drug therapy includes analgesics, NSAIDs and infiltration of a steroid. Chondroitin sulfates have an analgesic and functional effect proven. DMARDs such as hydroxychloroquine and methotrexate have been used successfully. Some patients also benefited from isotope synoviortheses. New therapeutic ways, based on the pathophysiology of the disease, are new under evaluation.


Assuntos
Antirreumáticos/uso terapêutico , Apatitas/metabolismo , Osteoartrite/terapia , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Glucocorticoides/uso terapêutico , Mãos , Humanos , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Osteoartrite/diagnóstico , Osteoartrite/fisiopatologia , Prognóstico
8.
Ann Rheum Dis ; 71(4): 560-2, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21998121

RESUMO

INTRODUCTION: Two subcutaneous injections of adalimumab in severe acute sciatica significantly reduced the number of back operations in a short-term randomised controlled clinical trial. OBJECTIVE: To determine in a 3-year follow-up study whether the short-term benefit of adalimumab in sciatica is sustained over a longer period of time. METHODS: The primary outcome of this analysis was incident discectomy. Three years after randomisation, information on surgery could be retrieved in 56/61 patients (92%).A multivariate Cox proportional hazard models, adjusted for potential confounders, was used to determine factors predisposing to surgery. RESULTS: Twenty-three (41%) patients had back surgery within 3 years, 8/29 (28%) in the adalimumab group and 15/27 (56%) in the placebo group, p=0.04. Adalimumab injections reduced the need for back surgery by 61% (HR)=0.39 (95% CI 0.17 to 0.92). In a multivariate model, treatment with a tumour necrosis factor-α antagonist remained the strongest protective factor (HR=0.17, p=0.002). Other significant predictors of surgery were a good correlation between symptoms and MRI findings (HR=11.6, p=0.04), baseline intensity of leg pain (HR=1.3, p=0.06), intensity of back pain (HR=1.4, p=0.03) and duration of sickness leave (HR=1.01 per day, p=0.03). CONCLUSION: A short course of adalimumab in patients with severe acute sciatica significantly reduces the need for back surgery.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciática/tratamento farmacológico , Doença Aguda , Adalimumab , Adulto , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Dor nas Costas/etiologia , Discotomia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ciática/complicações , Ciática/cirurgia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Arthritis Rheum ; 62(5): 1265-72, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20213811

RESUMO

OBJECTIVE: Alcohol consumption reduces the risk of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis in animal models. It remains unknown whether alcohol consumption influences joint damage progression in RA. This study was undertaken to compare the rates of radiographic damage progression in alcohol drinkers and nondrinkers in a large prospective cohort of patients with RA. METHODS: All patients in the population-based Swiss Clinical Quality Management in RA registry database with at least 2 sequential radiographs were included. Joint erosions were assessed in 38 joints in the hands and feet using a validated scoring method. The rate of progression of erosions was analyzed using multivariate regression models for longitudinal data and was adjusted for potential confounders. RESULTS: The study included 2,908 patients with RA with a mean of 4 sequential radiographs and 3.9 years of followup. A trend toward reduced radiographic progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of 0.99% (95% confidence interval [95% CI] 0.89-1.09) and 1.13% (95% CI 1.01-1.26) at 1 year, respectively. Alcohol consumption displayed a J-shaped dose-response effect, with a more favorable evolution in occasional consumers (P = 0.01) and daily consumers (P = 0.001) as compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P = 0.0001). We found significant effect modification by sex, with male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86% [95% CI 0.70-1.03] versus 1.35% [95% CI 1.02-1.67]; P = 0.007). CONCLUSION: Our findings indicate a trend toward reduced radiographic progression in alcohol drinkers compared with nondrinkers, specifically in occasional and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less radiographic progression than do male nondrinkers.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/epidemiologia , Sistema de Registros/estatística & dados numéricos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fatores de Risco , Comportamento de Redução do Risco , Distribuição por Sexo , Suíça/epidemiologia
10.
Ann Rheum Dis ; 69(2): 387-93, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19416802

RESUMO

BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Rituximab , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento
12.
RMD Open ; 6(1)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32385143

RESUMO

BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Abatacepte/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Suíça
13.
Vaccine ; 38(19): 3610-3617, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31911033

RESUMO

BACKGROUND: The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. METHODS: Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. RESULTS: A median time interval of 21.1 years (interquartile range 14.4-31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). CONCLUSION: The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.


Assuntos
Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Vacina contra Febre Amarela/imunologia , Febre Amarela , Anticorpos Antivirais , Humanos , Testes de Neutralização , Vacinação , Febre Amarela/prevenção & controle , Vírus da Febre Amarela
14.
Ann Rheum Dis ; 68(1): 33-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18230627

RESUMO

BACKGROUND: Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established. OBJECTIVE: To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA. METHODS: All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders. RESULTS: The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10-37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged. CONCLUSION: Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Análise de Variância , Artrite Reumatoide/diagnóstico por imagem , Artrografia , Fatores de Confusão Epidemiológicos , Progressão da Doença , Quimioterapia Combinada , Feminino , Humanos , Leflunomida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Rev Med Suisse ; 4(149): 728-30, 732-3, 2008 Mar 19.
Artigo em Francês | MEDLINE | ID: mdl-18472734

RESUMO

Behcet's syndrome (BS) is characterized by recurrent episodes of inflammatory manifestations, including oral and genital aphtosis, skin lesions, ocular attacks, arthritis, central nervous system and vascular manifestations (venous and arterial compartments). BS is more common in populations living in the ancient "silk road" from eastern Europe all the way to Japan. Several evidence suggest that both genetic and environmental factors are involved the pathogenesis. The association with the antigen HLA-B51 is observed with a highest frequency among patients of Middle Eastem countries and Japan. The diagnosis of BS is primarily established on clinical grounds in the absence of specific biological marker. The treatment is tailored according to the severity of clinical manifestations. The prognosis is more severe in young men.


Assuntos
Síndrome de Behçet/diagnóstico , Síndrome de Behçet/terapia , Síndrome de Behçet/classificação , Síndrome de Behçet/genética , Humanos , Prognóstico
19.
J Clin Invest ; 99(12): 2930-40, 1997 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-9185517

RESUMO

Interleukin 1 receptor antagonist (IL-1Ra) levels are elevated in the blood of patients with a variety of infectious, immune, or traumatic conditions. To examine whether IL1Ra is produced by liver cells with characteristics resembling an acute-phase protein, human primary hepatocytes isolated from liver biopsies and HepG2 hepatoma cells were stimulated with IL-1beta, IL-6, and TNFalpha. IL-1Ra was present in the supernatants of both cells, with production significantly enhanced by IL-1beta, and by the combination of IL-1beta and IL-6. The term IL-1Ra refers to two different proteins encoded by the same gene, but generated by alternative splicing of two different first exons. One isoform is secreted (17-kD sIL-1Ra), and the other isoform remains in the cytoplasm (18-kD icIL-1Ra). By Western blot analysis, the supernatants of human hepatoma (HepG2) cells contained only sIL-1Ra, whereas the lysates contained a novel smaller molecular mass isoform of 16 kD. RT-PCR and ribonuclease protection assay with RNA from HepG2 cells showed that only sIL-1Ra mRNA was expressed, and confirmed the inducing effect of IL-1beta and IL-6. Transfection studies were performed using constructs containing the promoters of either sIL-1Ra or icIL-1Ra coupled to the luciferase reporter gene. The sIL-1Ra promoter was active in HepG2 cells stimulated by IL-1beta and/or IL-6, whereas the icIL-1Ra promoter was inactive. Mutation of binding sites for transcription factors NF-kappaB and/or C/EBP within the proximal sIL-1Ra promoter led to significant decreases in response to IL-1beta and IL-6 in comparison to the wild-type promoter. Electromobility gel shift assays confirmed the presence of NF-kappaB and C/EBP binding sites within the sIL-1Ra promoter, and indicated a significant increase in the binding activities of nuclear proteins from HepG2 cells treated with IL-1beta and IL-6. In summary, sIL-1Ra, but not icIL-1Ra, is produced by hepatocytes, and is regulated by proinflammatory cytokines as an acute-phase protein. In addition, NF-kappaB and C/EBP family members are likely to play important roles in the full expression of IL-1Ra by hepatocytes during inflammatory conditions.


Assuntos
Proteínas de Fase Aguda , Fígado/metabolismo , Sialoglicoproteínas/biossíntese , Sítios de Ligação , Carcinoma Hepatocelular , Células Cultivadas , DNA/química , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Eletroforese , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Neoplasias Hepáticas , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Sialoglicoproteínas/genética , Transfecção , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia
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