Rheumatoid Arthritis: Majdan M

Kolarz B, Targońska-Stepniak B, Darmochwał-Kolarz D, Majdan M. · Katedra i Klinika Reumatologii i Układowych Chorób Tkanki Łacznej Akademii Medycznej im. prof. F. Skubiszewskiego w Lublinie, Lublin, Poland. · Postepy Hig Med Dosw (Online). · Pubmed #17786135 links to  free full text

Abstract: Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of such diseases as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and juvenile chronic arthritis. Recent years have brought improvement in the understanding of the pathogeneses of these diseases, resulting in the production of new groups of biological drugs, including, among others, anti-TNF-alpha antibodies. The use of TNF inhibitors has been a great advance in the treatment of patients with these inflammatory diseases. Infliximab and adalimumab are monoclonal antibodies that bind to and neutralize the activity of TNF-alpha. Infliximab is a mouse/human chimera that joins the variable regions of a mouse antibody to the constant region of human IgG1. Adalimumab is a fully human IgG1 antibody. Etanercept is a dimeric fusion protein that joins the human p75 TNF receptor to the Fc domain of human IgG1. The beneficial effects of the anti-TNF monoclonal antibodies infliximab and adalimumab and the soluble receptor fusion protein etanercept in the treatment of rheumatoid arthritis, especially in patients resistant to other disease-modifying antirheumatic drugs (DMARDs), are discussed. We observe stoppage of articular destruction during treatment with TNF-alpha inhibitors. Soon after the introduction of this therapy it was found that these agents have a propensity for stimulating the production of autoantibodies and antibodies against themselves. In this review, recent studies analyzing the effect of TNF-alpha blockade (infliximab, etanercept, and adalimumab) on the ANA, anti-dsDNA, and anticardiolipin antibody profiles in autoimmune diseases are discussed.

Parada-Turska J, Targońska-Stepniak B, Majdan M. · Katedra i Klinika Reumatologii i Układowych Chorób Tkanki Łacznej Akademii Medycznej im. prof. Feliksa Skubiszewskiego w Lublinie. · Postepy Hig Med Dosw (Online). · Pubmed #16715039 links to  free full text

Abstract: This paper presents interactions between prolactin (PRL) and the immune system. We describe the role of PRL in the pathogenesis of rheumatic diseases, particularly connective tissue diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome, systemic sclerosis, polymyalgia rheumatica, and seronegative arthritis. We present current opinion on the mechanisms responsible for hyperprolactinemia in SLE patients and the association between hyperprolactinemia and SLE activity and organ involvement. The role of dopamine receptor agonists in the treatment of connective tissue diseases is discussed.

Chrapko B, Zwolak R, Nocuń A, Gołebiewska R, Majdan M. · Chair and Department of Nuclear Medicine, Skubiszewski Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland. · Rheumatol Int. · Pubmed #17380335 No free full text.

Abstract: The aim of this study was to assess the effectiveness of radiation synovectomy (RSV) in the treatment of recurrent joint effusions, using 90Y in patients with chosen inflammatory joint diseases. The group of treated patients consisted of 30 people. Qualification for the treatment was based on clinical assessment, three-phase bone scintigraphy (BS3) and biochemical analysis. Intra-articular injection of 90Y was performed. Biochemical analysis was repeated after 48 h, 4 and 24 weeks, whereas BS3 was repeated after 24 weeks. Changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio. The changes in the blood pool phase before RSV were 3.4 +/- 0.6 and after the therapy 2.00 +/- 0.8 (P < 0.001). The J/B ratio was: before RSV 2.58 +/- 08; after treatment 2.09 +/- 0.9 (P < 0.05). RSV is an effective method to treat recurrent effusions in patients with RA and SPA.

Wielosz E, Majdan M, Koszarny A, Zychowska I. · Katedra i Klinika Reumatologii i Układowych Chorób Tkanki Łacznej, Akademia Medyczna, Lublin. · Pol Arch Med Wewn. · Pubmed #18778028 links to  free full text

Abstract: We describe the case a 63-year-old man with overlap of primary Sjögren syndrome (pSS) and antiphospholipid syndrome (APS). According to literature the presence of antiphospholipid antibodies is observed in about 20% of patients with pSS. The coexistence of pSS and APS should be considered as an infrequent, but not exceptional, event.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Parada-Turska J, Mitura A, Brzana W, Jabłoński M, Majdan M, Rzeski W. · Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland. · Inflammation. · Pubmed #18568393 No free full text.

Abstract: Parthenolide is a bioactive constituent of an aromatic herb Feverfew (Tanacetum parthenium). It has been found that both parthenolide and extract of feverfew have anti-inflammatory and antinociceptive properties. Moreover, they demonstrate antiproliferative activities on different human tumour cells. The massive hyperplasia of synovial fibroblasts is the one of the most striking features of rheumatoid arthritis. It is not known whether this is due to the proliferation of synovial fibroblasts or to defective apoptosis. We investigated the effect of parthenolide on the proliferation of rabbit synoviocytes cell line HIG-82, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and human skin fibroblasts (HSF) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5'-bromo-2'-deoxy-uridine methods. Parthenolide inhibited proliferation of HIG-82 and human RA-FLS. The proliferation of HSF was inhibited less effectively. The antiproliferative potential of parthenolide was demonstrated.

Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, Anonymous00244. · Hospital de Gran Canaria Dr, Negrin, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n 35011, Spain. · Arthritis Res Ther. · Pubmed #18325087 links to  free full text

Abstract: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Targońska-Stepniak B, Majdan M, Dryglewska M. · Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, ul. Jaczewskiego 8, 20-950 Lublin, Poland. · Rheumatol Int. · Pubmed #17968549 No free full text.

Abstract: Leptin is a peptide hormone with the tertiary structure of a cytokine, which not only regulates body weight by inhibiting food intake, but also modulates inflammatory and immune responses. The aim of the study was to investigate if there are connections between leptin concentrations and parameters of nutritional status and disease activity in a group of rheumatoid arthritis (RA) patients. The study group consisted of 37 patients. The mean leptin serum concentration was significantly higher in women than in men. The leptin concentrations correlated positively with BMI only in women with RA. The leptin concentrations were significantly higher in patients with erosive RA. Assessing the group of patients with long-standing RA (duration > 10 years), we found that leptin levels were significantly higher in patients with higher disease activity than in those with DAS28 < or = 5,1; there was also a positive correlation between serum leptin concentration and the value of DAS28, ESR and the number of tender joints. The results suggest that some important dependence exists between the risk of aggressive course of RA and increased leptin levels.

Parada-Turska J, Rzeski W, Majdan M, Kandefer-Szerszeń M, Turski WA. · Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland. · Eur J Pharmacol. · Pubmed #16533508 No free full text.

Abstract: One of the most striking features of inflammatory arthritis is the hyperplasia of synovial fibroblasts. It is not known whether the massive synovial hyperplasia characteristic of rheumatoid arthritis is due to the proliferation of synovial fibroblasts or to defective apoptosis. It has been found that glutamate receptor antagonists inhibit proliferation of different human tumour cells and the anticancer potential of glutamate receptor antagonists was suggested. Here, we investigated the effect of glutamate receptor antagonists and selected antirheumatic drugs on proliferation of synoviocytes in vitro. Experiments were conducted on rabbit synoviocytes cell line HIG-82 obtained from American Type Culture Collection (Menassas, VA, USA). Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC50 value (the concentration of drug necessary to induce 50% inhibition) together with confidence limits was calculated. Glutamate receptor antagonists, 1-(4-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one (CFM-2), riluzole, memantine, 1-4-aminophenyl-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), dizocilpine, ketamine and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), inhibited proliferation of synoviocytes with the following IC50 values (in mM): 0.014, 0.017, 0.065, 0.102, 0.15, 0.435 and 1.16, respectively. Antirheumatic drugs, celecoxib, diclofenac, nimesulide, sulfasalazine, naproxen and methotrexate, inhibited proliferation of synoviocytes with the following IC50 values (in mM): 0.0043, 0.034, 0.044, 0.096, 0.385 and 1.123, respectively. Thus, the antiproliferative potential of glutamate receptor antagonists is comparable to that of antirheumatic drugs.

Parada-Turska J, Rzeski W, Zgrajka W, Majdan M, Kandefer-Szerszeń M, Turski W. · Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-950 Lublin, Poland. · Rheumatol Int. · Pubmed #16220290 No free full text.

Abstract: Kynurenic acid is an antagonist of ionotropic glutamate receptors. It has been found that glutamate antagonists inhibit proliferation of different human tumor cells. Since the hyperplasia of synovial fibroblasts is one of the most striking features of inflammatory arthritis, the main goals of this study were detection and quantification of kynurenic acid in synovial fluid obtained from patients with rheumatoid arthritis, and determination of its effect on proliferation of synoviocytes in vitro. Presence of kynurenic acid was determined by HPLC in all 58 samples of synovial fluid. The mean concentration was 15.89 pmol/ml. Kynurenic acid inhibited synoviocyte proliferation with the IC50 value of 5.9 mM. In subthreshold concentration of 0.3 mM it enhanced antiproliferative action of celecoxib and nimesulide. In conclusion, the presence of kynurenic acid in synovial fluid was documented in patients with rheumatoid arthritis. Its potential role as an endogenous substance, controlling synoviocyte proliferation can be suggested.

Majdan M, Stepniak C, Piotrowicz S, Broniek K, Blajer B, Bednarek-Skublewska A. · Katedra i Klinika Reumatologii i Układowych Chorób Tkanki Lacznej. · Pol Arch Med Wewn. · Pubmed #16209247 No free full text.

Abstract: The chronic nephropathy is often present in pts with rheumatoid arthritis (RA). In the study the authors retrospectively analyzed the clinical course of the disease and outcomes of subsequent dialysotherapy in a group of pts with RA and end-stage renal disease ESRD. During last 5 years ESRD connected with RA was found in 10 (8 F, 2 M) pts out of 325 chronically dialyzed pts (peritoneal dialysis and hemodialysis) representing 3,1% of pts. The mean age at the initiation of dialysotherapy in these pts was 62,8 +/- 10,2 (range 46-76) years. Mean time from the diagnosis of RA to the start of dialysotherapy was 18,8 +/- 11,6 (range 5-40) years. Earlier the patients were treated with many disease modifying antirheumatic drugs (DMARDS) also with glucocorticosteroids and many nonsteroidal anti-inflammatory drugs. It means that they had rather aggressive type of RA. Amyloidosis was histological confirmed in 6 pts (4 F, 2 M). Peritoneal dialysis (PD) was the first choice therapy in 8 pts (2 on APD, 6 on CAPD). The main complication was increased incidence of peritonitis. 3 pts died on PD after 5, 9, 24 months (respectively) of CAPD treatment. 3 pts were transferred to HD after 5, 15, 18 (respectively) months of CAPD because of recurrent peritonitis. 2 pts up to date continue PD (one 12 months, the second 46 months on CAPD). In 5 pts who needed hemodialysis treatment there have been very serious problems with permanent vascular access formation. All used permanent indwelling catheters (Permcath). We concluded that: occurrence of ESRD in pts with RA was connected with aggressive type of disease. Pts with RA represent a dialysis group that is particularly prone to complications of PD (enteric peritonitis) and HD (vascular access problems). It seems to be connected with secondary vasculitis often found in pts with aggressive type of RA.