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Horvath K.,Zsigmondy Vilmos Harkany Medicinal Spa Hospital | Kulisch A.,Spa Heviz And St Andrew Hospital For Rheumatic Diseases P U C | Nemeth A.,NK Medicor Ltd | Bender T.,Polyclinic Of The Hospitaller Brothers Of St John Of God
Clinical Rehabilitation | Year: 2012

Objective: To evaluate the effectiveness of thermal mineral water compared with magnetotherapy without balneotherapy as control, in the treatment of hand osteoarthritis. Design: Randomized controlled single-blind follow-up study. Setting: Rheumatology specialist clinic of Gunaras Health Spa. Subjects: Patients between 50 and 70 years of age with hand osteoarthritis, randomly assigned into three groups. Interventions: The subjects in the first two groups bathed in thermal mineral water of two different temperatures (36°C and 38°C) for three weeks five times a week for 20 minutes a day and received magnetotherapy to their hands three times weekly. The third group received only magnetotherapy. Outcome measures: Visual analogue scale scores, handgrip strength, pinchgrip strength, the number of swollen and tender joints of the hand, the duration of morning joint stiffness, Health Assessment Questionnaire, and Short Form-36 questionnaire. The study parameters were administered at baseline, immediately after treatment and after 13 weeks. Results: The study included 63 patients. Statistically significant improvement was observed in several studied parameters after the treatment and during the follow-up study in the thermal water groups versus the control group. The 38°C thermal water treatment significantly improved the pinch strength of the right hand (0. 6 (95% confidence interval (CI) 0. 2 to 1. 1) vs. 0. 03 (95% CI -0. 3 to 0. 4), P < 0. 05) and the Health Assessment Questionnaire parameters (-0. 4 (95% CI -0. 6 to -0. 2) vs. -0. 1 (95% CI -0. 2 to 0. 1), P < 0. 01) even in the long term. Conclusions: Balneotherapy combined with magnetotherapy improved the pain and function as well as the quality of life in patients with hand osteoarthritis. © 2011 The Author(s).


Dougados M.,University of Paris Descartes | Dougados M.,Cochin Hospital | Braun J.,Rheumazentrum Ruhrgebiet | Szanto S.,Debrecen University | And 5 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objectives: Patients with advanced ankylosing spondylitis (AS) experience disability because of reduced spinal mobility and pulmonary function impairment. This placebo-controlled study evaluated the effect of etanercept (ETN) in patients with advanced AS. Methods: A multicentre randomised double-blind placebo-controlled trial of 12 weeks' duration was performed. Patients had definite (modified New York criteria), active (Bath AS Disease Activity Index (BASDAI) ≥40), severe (radiological intervertebral bridges) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive. They were treated with ETN 50 mg once weekly or identical placebo (PBO). Results: Of the 95 patients screened, 82 were randomised to receive ETN (n=39) or PBO (n=43). At baseline the disease was active (mean BASDAI 61.0±13.4, C reactive protein (CRP) 20.7±25.5 mg/l) and severe (mean Bath AS Metrology Index (BASMI) 5.7±1.3, mSASSS 36.5±20.5);forced pulmonary vital capacity (FVC) was 3.3±0.7 l. Improvement in BASDAI (normalised net incremental area under the curve between baseline and week 12, primary end point) was significantly greater in the ETN group than in the PBO group (-19.8±16.5 vs-11.0±16.4, p=0.019). Moreover, at week 12, ETN gave better results than PBO for the BASDAI (-26.4±19.7 vs -14.4±19.7;p=0.008), total back pain (-29.2±24.0 vs-14.9±24.0;p=0.010), BASFI (-21.7±17.6 vs-10.1±17.6;p=0. 004), BASMI (-0.6±0.6 vs -0.2±0.6;p=0.011), CRP level (-15.7±14.2 vs -1.3±14.2;p<0.001) and FVC (+160±280 ml vs -20±280 ml;p=0.006). Conclusions: ETN has short-term efficacy for patients with advanced AS, as was previously reported for less advanced disease. The efficacy is observed for the main symptoms (pain) and on markers of inflammation (CRP), as well as disease severity in terms of spinal mobility and pulmonary function.


Tefner I.K.,Jozsefvaros Health Care Services | Nemeth A.,NK Medicor Kft | Laszlofi A.,Mofetta and Thermal Spa | Kis T.,Mofetta and Thermal Spa | And 2 more authors.
Rheumatology International | Year: 2012

Effect of thermal water with high mineral content on clinical parameters and quality of life of patients with chronic low back pain was studied. In this randomized controlled, single-blind, follow-up study, 60 patients with chronic low back pain were randomized into two groups. The treatment group received balneotherapy with thermal-mineral water, and the control group bathed in tap water. Changes of the followings were evaluated: visual analogue scale (VAS) for pain, range of motion for the lumbar spine, Oswestry index, EuroQol-5D and Short Form-36 questionnaires. In the treatment group, the mobility of the lumbar spine, the Oswestry index, the VAS scores and the EuroQoL-5D index improved significantly. SF-36 items improved significantly in the treated group compared with baseline except for two parameters. Our study demonstrated the beneficial effect of balneotherapy with thermal mineral versus tap water on clinical parameters, along with improvements in quality of life. © 2011 Springer-Verlag.


Bender T.,Polyclinic Of The Hospitaller Brothers Of St John Of God | Bender T.,University of Szeged | Balint G.,National Institute of Rheumatology and Physiotherapy | Prohaszka Z.,Semmelweis University | And 3 more authors.
International Journal of Biometeorology | Year: 2014

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis. © 2013 The Author(s).


Szili D.,Eötvös Loránd University | Cserhalmi M.,Eötvös Loránd University | Banko Z.,Eötvös Loránd University | Nagy G.,Polyclinic Of The Hospitaller Brothers Of St John Of God | And 2 more authors.
mAbs | Year: 2014

The Fc receptor (FcγRIIb) inhibits B cell responses when coengaged with B cell receptor (BCR), and has become a target for new autoimmune disease therapeutics. For example, BCR and FcγRIIb coengagement via the Fc-engineered anti-CD19 XmAb5871 suppresses humoral immune responses. We now assess effects of XmAb5871 on other activation pathways, including the pathogen-associated molecular pattern receptor, TLR9. Since TLR9 signaling is implicated in autoimmune diseases, we asked if XmAb5871 could inhibit TLR9 costimulation. We show that XmAb5871 decreases ERK and AKT activation, cell proliferation, cytokine, and IgG production induced by BCR and/or TLR9 signals. XmAb5871 also inhibited differentiation of citrullinated peptide-specific plasma cells from rheumatoid arthritis patients. XmAb5871 may therefore have potential to suppress pathogenic B cells in autoimmune diseases. © 2014 Landes Bioscience.


Dougados M.,University of Paris Descartes | Braun J.,Rheumazentrum Ruhrgebiet | Szanto S.,Debrecen University | Combe B.,Montpellier University | And 3 more authors.
Rheumatology (United Kingdom) | Year: 2012

Objective. To evaluate the longer-term efficacy of etanercept in patients with severe and advanced active AS.Methods. Seventy-seven patients who completed the randomized, double-blind, placebo-controlled 12-week SPINE study enrolled in a 12-week open-label extension and received s.c. etanercept 50 mg once weekly. The etanercept/etanercept group received a total of 24 weeks treatment with etanercept (n = 38); the placebo/etanercept group received placebo during the double-blind study then 12 weeks' etanercept treatment during the open-label extension (n = 39).Results. At the end of the open-label extension, BASDAI scores in the etanercept/etanercept group had further decreased beyond reductions observed during the double-blind study [mean (s.d.) change from baseline -37.6 (22.4) at end of extension vs -27.4 (23.8) at end of double-blind study]. Mean (s.d.) BASDAI scores also improved in the placebo/etanercept group once switched to etanercept [-28.6 (24.3) vs -15.0 (20.0)]. Similar trends were observed in BASFI and BASMI scores. In the placebo/etanercept group, total back pain decreased to similar levels achieved in the etanercept group in the double-blind study. Pain levels continued to decrease with longer-term etanercept therapy in the etanercept/etanercept group.Conclusion. Despite the improvements in symptoms and inflammatory markers observed shortly after initiation of once-weekly etanercept, there was no notable plateauing effect on patient-reported outcomes. Indeed, signs and symptoms of severe and advanced active AS continued to improve after up to 24 weeks, treatment with etanercept. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Buzas E.I.,Semmelweis University | Gyorgy B.,Semmelweis University | Nagy G.,Polyclinic of the Hospitaller Brothers of St John of God | Falus A.,Semmelweis University | Gay S.,University of Zürich
Nature Reviews Rheumatology | Year: 2014

The discovery that submicron-sized extracellular vesicles (EVs) are generated by both prokaryotic and eukaryotic cells might have a profound effect on experimental and clinical sciences, and could pave the way for new strategies to combat various diseases. EVs are carriers of pathogen-associated and damage-associated molecular patterns, cytokines, autoantigens and tissue-degrading enzymes. In addition to a possible role in the pathogenesis of a number of inflammatory conditions, such as infections and autoimmune diseases, EVs, including microvesicles (also known as microparticles), exosomes and apoptotic vesicles, have therapeutic potential and might be used as biomarkers for inflammatory diseases. Therefore, molecular diagnostics and targeted therapy could benefit from expanding knowledge in the field. In this Review, we summarize important developments and propose that extracellular vesicles could be used as therapeutic vehicles and as targets for the treatment and prevention of inflammatory diseases. © 2014 Macmillan Publishers Limited.


PubMed | Polyclinic of the Hospitaller Brothers of St John of God, University of Zürich and Semmelweis University
Type: Journal Article | Journal: Nature reviews. Rheumatology | Year: 2014

The discovery that submicron-sized extracellular vesicles (EVs) are generated by both prokaryotic and eukaryotic cells might have a profound effect on experimental and clinical sciences, and could pave the way for new strategies to combat various diseases. EVs are carriers of pathogen-associated and damage-associated molecular patterns, cytokines, autoantigens and tissue-degrading enzymes. In addition to a possible role in the pathogenesis of a number of inflammatory conditions, such as infections and autoimmune diseases, EVs, including microvesicles (also known as microparticles), exosomes and apoptotic vesicles, have therapeutic potential and might be used as biomarkers for inflammatory diseases. Therefore, molecular diagnostics and targeted therapy could benefit from expanding knowledge in the field. In this Review, we summarize important developments and propose that extracellular vesicles could be used as therapeutic vehicles and as targets for the treatment and prevention of inflammatory diseases.


Inotai A.,Semmelweis University | Rojkovich B.,Polyclinic Of The Hospitaller Brothers Of St John Of God | Fulop A.,Polyclinic Of The Hospitaller Brothers Of St John Of God | Jaszay E.,Polyclinic Of The Hospitaller Brothers Of St John Of God | And 2 more authors.
Rheumatology International | Year: 2012

Biological treatments earn increasing significance in the treatment of rheumatoid arthritis (RA) but are associated with high incremental cost-effectiveness ratio compared to conventional antirheumatic treatments such as disease-modifying antirheumatic drugs. As the most important objective of medical technologies should be to increase life years and/or patients' health-related quality of life (HRQoL), measuring QoL and utility in RA patients treated with biological therapies is crucial. The objective of this study is to compare the utility and QoL of patients treated with biological (n = 85) and non-biological (n = 168) antirheumatic drugs in Hungary in a cross-sectional non-interventional study. A measure of impairment (Disease Activity Score (DAS)-28), QoL measure (Euro-Qol five Dimension (EQ-5D) Visual Analogue Scale (VAS), Rheumatoid Arthritis Quality of Life (RAQoL)) and utility measures (indirect: EQ-5D index, direct: time trade-off (TTO)) were applied using an interview method. The Pearson correlation was used to assess the strength of the relationship of different measures in the total study group (n = 253). The EQ-5D index (biological treatment: 0.608, non-biological treatment: 0.483; P = 0.012) and DAS-28 (biological treatment: 3.8, non-biological treatment: 4.5; P = 0.003) showed statistically significant difference between the two subcohorts after adjusting data by age, gender and disease duration. Our results indicate that patients on biological treatment have lower disease activity and higher utility; however, it was not statistically significant in all cases. According to our knowledge, TTO was not used previously in Hungarian RA patients. Utility data concerning biological treatments are essential for costutility models in health technology assessment reports for public reimbursement. © Springer-Verlag 2011.


PubMed | Polyclinic Of The Hospitaller Brothers Of St John Of God and Eötvös Loránd University
Type: | Journal: Arthritis research & therapy | Year: 2016

Autoreactive B cells are crucial players in the pathogenesis of rheumatoid arthritis (RA). Autoantibodies specific for citrullinated proteins (ACPA), present in the serum of approximately 60-70% of patients, have a pathogenic role in the disease. B cell depleting therapies may result in a transient immunosuppression, increasing the risk of infections. Our aim was to develop a new therapeutic approach to selectively deplete the ACPA producing autoreactive B cells.To target B cells synthetic citrullinated peptide derived from the chain of fibrin, 60-74Cit 60,72,74 (60-74Cit), the predominant epitope recognized by ACPA was used. Complement dependent cytotoxicity (CDC) was induced by a modified peptide derived from gp120 of HIV-1. To trigger CDC both the targeting peptide and the complement activating peptide were covalently coupled in multiple copies to the surface of poly (DL-lactic-co-glycolic acid) nanoparticles (NPs). Ex vivo antibody synthesis was examined by ELISA and ELISpot. CDC was tested after dead cell staining by flow cytometry.The 60-74Cit peptide was selectively recognized by a small subset of B cells from RA patients having high level of peptide specific serum antibody, suggesting that the peptide can target diseased B cells. The modified gp120 peptide covalently coupled to NPs induced the formation of the complement membrane attack complex, C5b-9 in human serum. We show here for the first time that bifunctional NPs coupled to multiple copies of both the targeting peptide and the complement activating effector peptide on their surface significantly reduce 60-74Cit peptide specific ex vivo ACPA production, by inducing complement dependent lysis of the citrullinated peptide specific B cells of seropositive RA patients.Bifunctional NPs covalently coupled to autoantigen epitope peptide and to a lytic peptide activating complement may specifically target and deplete the peptide specific autoreactive B-cells.

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