Rheumatoid Arthritis: Finland

Sokka T. · Jyväskylä Central Hospital, Jyväskylä 40620, Finland. · Curr Opin Rheumatol. · Pubmed #19342954 No free full text.

Abstract: PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is recognized as a disease with a natural history of severe long-term outcomes, which appear to be improving at this time, as reported from many clinics. RECENT FINDINGS: Improved outcomes of many long-term consequences of inflammation such as joint deformity, functional declines, work disability, and early death have been reported in recent years. SUMMARY: Therapies for RA are assessed in randomized clinical trials and in clinical care primarily according to measures of inflammatory activity, which may change considerably over days, weeks, and months. In usual clinical care, long-term consequences of the disease, which often require years of observation, can also be assessed. Data in published reports of both clinical trials and clinical care continue to include only a minority of all patients with RA. Further efforts are needed to promote collection of quantitative data in all patients with RA, at all visits in all clinical settings, to facilitate 'tight control' and better outcomes for all patients with RA.

Sokka T, Mäkinen H. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Best Pract Res Clin Rheumatol. · Pubmed #19233049 No free full text.

Abstract: Modern therapy of rheumatoid arthritis (RA) is based on recognition of the severity of the natural history of disease, with early and aggressive treatment strategies. Methotrexate is the anchor drug, with addition of other disease-modifying anti-rheumatic drugs (DMARDs) in combinations, and biological targeted therapies. The approach emphasizes 'tight control', aiming for remission and low disease activity according to quantitative monitoring. In this chapter, we review selected randomized controlled studies for data concerning early versus delayed therapies. We present a historical perspective for the treatment of early RA using early RA cohorts from Finland as an example. Finally, we discuss principles of contemporary treatment of early RA in 2008.

Korhonen R, Moilanen E. · The Immunopharmacology Research Group, Medical School, University of Tampere, and Research Unit, Tampere University Hospital, Finland. · Basic Clin Pharmacol Toxicol. · Pubmed #19228144 No free full text.

Abstract: Rheumatoid arthritis is a chronic systemic inflammatory disease with major articular manifestations. While its aetiology still remains to be resolved, our understanding on the pathogenesis of rheumatoid arthritis has become clearer during two decades enlightening the role of adaptative immunity in the development of the symptoms and signs as well as in the progression of the pathological articular changes taking place in inadequately controlled disease. T lymphocytes are considered to be an important cell type in the pathogenesis of rheumatoid arthritis through production of proinflammatory cytokines, promotion of formation of ectopic lymphoid structures and neovascularization in synovial tissue, promotion autoantibody production by B cells, and activation of synoviocytes and osteoclasts. Abatacept, a CTLA4-Ig fusion protein, represents a new therapeutic approach in rheumatoid arthritis. Abatacept attenuates T cell activation as it regulates the activation of T cells by inhibiting the CD80/86:CD28 co-stimulatory pathway that is required for the proper T cell activation. This MiniReview gives an overview on the mechanism of action of abatacept and summarizes the published clinical data on abatacept in the treatment of rheumatoid arthritis.

Pirttiniemi P, Peltomäki T, Müller L, Luder HU. · Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu, Finland. · Eur J Orthod. · Pubmed #19164410 No free full text.

Abstract: Deviations in the growth of the mandibular condyle can affect both the functional occlusion and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and often entail complex sequences of malfunction at the cellular level. The aim of this review is to summarize recent progress in the understanding of pathological alterations occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence, result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into (1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3) acquired diseases or trauma with associated growth disorders. Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other craniofacial dysplasias seem far less prominent than could be anticipated based on their often disfiguring nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally, disturbances of mandibular growth as a result of juvenile idiopathic arthritis (JIA) and condylar fractures seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage.

Sokka T, Abelson B, Pincus T. · Department of Medicine, Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #19026144 No free full text.

Abstract: Mortality rates in patients with rheumatoid arthritis (RA) are 1.5-1.6 fold higher than in the general population, with similar patterns over 60 years. The acute attributed causes of death appear overall similar to the general population, with cardiovascular disease the most common attributed cause of death, and with more infection, pulmonary and renal disease in RA than in the general population. All clinical measures indicating more severe clinical status appear prognostic of premature mortality, with rheumatoid factor and the shared epitope significant for progressive RA. Functional and global measures as well as comorbidities generally are the most significant predictors of premature death.

Sokka T, Häkkinen A. · Department of Medicine, Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #19026141 No free full text.

Abstract: Poor physical function and low muscle strength are significant predictors of mortality in rheumatoid arthritis, other chronic diseases, ageing individuals, and the general population. Poor physical function predicts earlier mortality in diseased and normal populations at levels of significance similar to or greater than most known biomedical predictors such as laboratory tests. This chapter summarizes data concerning the prediction of premature mortality by poor physical fitness and musculoskeletal function, according to performance and self-report measures. The data support recommendations for regular exercise in all individuals whether or not they have a disease, to promote health and longevity.

Sokka T, Envalds M, Pincus T. · Arkisto/Tutkijat, Jyväskylä Central Hospital, Jyvaskyla, Finland. · Mod Rheumatol. · Pubmed #18437286 links to  free full text

Abstract: Modern therapy for rheumatoid arthritis (RA) is based on knowledge of the severity of the natural history of the disease. RA patients are approached with early and aggressive treatment strategies, methotrexate as an anchor drug, biological targeted therapies in those with inadequate response to methotrexate, and "tight control," aiming for remission and low disease activity according to quantitative monitoring. This chapter presents a rationale for current treatment strategies for RA with antirheumatic drugs, a review of published reports concerning treatments in clinical cohorts outside of clinical trials, and current treatments at 61 sites in 21 countries in the QUEST-RA database.

Rauvala H, Rouhiainen A. · Neuroscience Center, University of Helsinki, Helsinki, Finland. · Curr Mol Med. · Pubmed #18331230 No free full text.

Abstract: HMGB1/Amphoterin is a ubiquitous, highly conserved DNA-binding protein that can be also released to the extracellular space by various cell types. Extracellular HMGB1 regulates migratory responses of several cell types through binding to RAGE that communicates with the cytoskeleton to regulate cell motility. HMGB1-induced cell signalling has been associated with mechanisms of several diseases, including cancer, sepsis, rheumatoid arthritis, stroke and atherosclerosis. This article reviews the evidence linking the functional roles of HMGB1 to RAGE signalling. Furthermore, we discuss the molecular and cellular mechanisms that may explain the roles of HMGB1/RAGE in diverse disease processes.

Porola P, Laine M, Virkki L, Poduval P, Konttinen YT. · Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. · Ann N Y Acad Sci. · Pubmed #17894007 No free full text.

Abstract: Sjögren's syndrome is an autoimmune disease affecting the exocrine glands, most typically salivary and lacrimal glands. In Sjögren's syndrome, the acinar cells of these glands are damaged and destroyed, leading to diminished secretion of saliva and tear fluid. Accordingly, the current American-European criteria of Sjögren's syndrome include xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). In addition to these sicca symptoms and signs, the diagnostic criteria require autoimmune features in the form of Sjögren's syndrome SS-A and/or SS-B autoantibodies and lymphocyte infiltrates in labial salivary glands. Majority of patients with Sjögren's syndrome are women and the diagnosis is usually done when they are 40-50 years old. The cause of Sjögren's syndrome is unknown, but taking into account the female dominance and the late onset, our hypothesis is that sex steroids play a key role in the etiology of Sjögren's syndrome. More specifically, we believe that the driving factor behind Sjögren's syndrome could be lack of androgens. It has been shown that patients with Sjögren's syndrome have low concentrations of circulating dehydroepiandrosterone sulfate (DHEA-S) compared to age-matched healthy controls. Our hypothesis is that patients with Sjögren's syndrome suffer from an insufficient local androgen effect in the exocrine target tissues of the disease because of low systemic levels and/or ineffective local intracrine handling of DHEA-S prohormone. To further clarify the role of sex steroids and the eventual deficiency of androgens, salivary glands are studied using protein markers regulated by androgens or estrogens.

Rautemaa R, Lauhio A, Cullinan MP, Seymour GJ. · Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland. · Clin Microbiol Infect. · Pubmed #17714525 No free full text.

Abstract: The relationship between oral and general health has been increasingly recognised during the past two decades. Several epidemiological studies have linked poor oral health with cardiovascular disease, poor glycaemic control in diabetics, low birth-weight pre-term babies, and a number of other conditions, including rheumatoid arthritis and osteoporosis. Oral infections are also recognised as a problem for individuals suffering from a range of chronic conditions, including cancer and infection with human immunodeficiency virus, as well as patients with ventilator-associated pneumonia. This review considers the systemic consequences of odontogenic infections and the possible mechanisms by which oral infection and inflammation can contribute to cardiovascular disease, as well as the oral conditions associated with medically compromised patients. A large number of clinical studies have established the clinical efficacy of topical antimicrobial agents, e.g., chlorhexidine and triclosan, in the prevention and control of oral disease, especially gingivitis and dental plaque. The possible risks of antimicrobial resistance are a concern, and the benefits of long-term use of triclosan require further evaluation. Oral infections have become an increasingly common risk-factor for systemic disease, which clinicians should take into account. Clinicians should increase their knowledge of oral diseases, and dentists must strengthen their understanding of general medicine, in order to avoid unnecessary risks for infection that originate in the mouth.

Eklund KK. · Division of Rheumatology, Helsinki University Central Hospital, Helsinki, Finland. · Immunol Rev. · Pubmed #17498050 No free full text.

Abstract: Increasing evidence suggests that mast cells (MCs), in addition to acute allergic reactions, are involved in the pathogenesis of chronic inflammatory diseases and in particular in rheumatoid arthritis (RA). MCs reside in connective tissues and in synovial tissue of joints. They produce an array of proinflammatory mediators, tissue destructive proteases, and cytokines, most prominently tumor necrosis factor-alpha, which is one of the key cytokines in the pathogenesis of RA. MCs may also participate in the development of secondary or amyloid A amyloidosis, as the partial degradation of the serum amyloid A (SAA) protein by MCs leads to the generation of a highly amyloidogenic N-terminal fragment of SAA. MCs may contribute to the pathogenesis of connective tissue diseases, scleroderma, vasculitic syndromes, and systemic lupus erythematosus, although the data available are limited. Inhibition of the most important growth factor receptor of human MCs, c-Kit, by the selective tyrosine kinase inhibitor imatinib mesylate, induces apoptosis of synovial tissue MCs. As MCs are long-lived cells, induction of their apoptosis could be a feasible approach to inhibit their functions. Preliminary findings suggest that a drug that inhibits c-Kit could have anti-rheumatic activity in the treatment of patients with RA and spondyloarthropathies.

Salminen-Mankonen HJ, Morko J, Vuorio E. · Department of Medical Biochemistry and Molecular Biology, University of Turku, FI-20520 Turku, Finland. · Curr Drug Targets. · Pubmed #17305509 No free full text.

Abstract: Cysteine cathepsins are a large family of proteolytic enzymes active at acidic pH as found in lysosomes. Since its discovery in 1990's, cathepsin K has been shown to be a key enzyme in osteoclastic bone resorption through its activity in the resorption lacuna. Although characteristic to osteoclasts, the expression of cathepsin K has also been observed at other sites in skeleton. Several recent observations have demonstrated up-regulation of cathepsin K in osteoarthritic cartilage and inflamed synovial tissue. As cathepsin K is one of the few extracellular proteolytic enzymes capable of degrading native fibrillar collagen, it may play an important role in the progressive destruction of articular cartilage both in osteoarthritis and in inflammatory arthritides. Also transgenic mouse models have provided evidence supporting the important role of cathepsin K in both groups of arthritides. The aim of this chapter is to review the accumulating evidence for the role of cathepsin K in degradation of articular cartilage regardless of its pathogenic background, and to discuss the potential efficacy of cathepsin K inhibitors to slow down or prevent articular cartilage degradation.

Franssila R, Hedman K. · Department of Virology, Haartman Institute, University of Helsinki and HUCH Laboratory Division, Haartmaninkatu 3, FI-00290 Helsinki, Finland. · Best Pract Res Clin Rheumatol. · Pubmed #17127201 No free full text.

Abstract: Several viruses cause postinfectious arthritis. The disease is a typical manifestation of arthritogenic alphaviruses, rubella virus and human parvovirus B19. In addition, arthritis is not uncommon after infection by HIV, cytomegalovirus, hepatitis B virus, hepatitis C virus, or Epstein-Barr virus (EBV). Also prolonged arthritis may result from viral infections, particularly with alphaviruses and human parvovirus B19. Viruses such as EBV and B19 may have significant roles in initiating chronic arthropathies, which in some cases may be indistinguishable from rheumatoid arthritis.

Konttinen YT, Porola P, Konttinen L, Laine M, Poduval P. · Department of Medicine, FIN-00029 HUS, Finland. · Autoimmun Rev. · Pubmed #17110311 No free full text.

Abstract: Sjögren's syndrome (SS) is characterized by keratoconjunctivitis sicca and xerostomia, which occur in an autoimmune lacrimal and salivary gland disease characterized by lymphocyte infiltrates of exocrine glands and/or Sjögren's syndrome autoantibody production. It has been reported that aquaporin-5 distribution is abnormal in SS, perhaps as a result of paracrine effect of TNF-alpha. Also the neurogenic regulation of the salivary gland is impaired in SS. Apart from functional changes, the syndrome is also characterized by structural abnormalities of the secretory acinar apparatus. The acinar basement membrane is abnormal as it lacks laminin alpha1 chain, which may impair its capability to induce the progenitor cells to differentiate to acinar cells. CRISP-3 and TMPRSS-2 can be used as androgen markers and LIV-1 and Cyr61 as estrogen markers to study the sexual dimorphism of the salivary glands. Patients with SS seem to have low concentrations of dehydroepiandrosterone, which may predispose women and the exocrine glands to this syndrome.

Hilden TJ, Nurmi SM, Fagerholm SC, Gahmberg CG. · Division of Biochemistry, Faculty of Biosciences, University of Helsinki, Finland. · Ann Med. · Pubmed #17101541 No free full text.

Abstract: Inflammation is a crucial response against invading pathogens, in which immune cells, including neutrophils and T cells, are recruited into tissue from the bloodstream to help clear infection. However, a prevailing inflammatory response where the immune cells attack healthy tissue is associated with many diseases, including asthma, rheumatoid arthritis, atherosclerosis and multiple sclerosis. Integrins are key players in the recruitment of immune cells from the bloodstream into tissues, and are thus therapeutic targets for intervention with inflammatory responses. Thus far, mainly extracellularly acting therapeutics (monoclonal antibodies) have been developed against integrins, targeting ligand binding sites in these heterodimeric adhesion receptors. However, since these therapeutics nonselectively block all integrin functions, some side effects are expected and have been observed. Therefore, novel concepts need to be developed in the therapeutic targeting of integrins. Recently, major advances have been made in the understanding of integrin biology. Integrin structures have been solved by X-ray crystallography, revealing unexpected data about the activation mechanism of integrins in cells. Additionally, several intracellular factors in the integrin activation process have been identified, providing potential specific targets for therapeutic intervention. Here, we present key events and players in leukocyte integrin activation, and discuss potential new drug targets in the prevention of inflammatory disease.

Mäkinen H, Hannonen P, Sokka T. · Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #17083758 No free full text.

Abstract: Various definitions of remission in rheumatoid arthritis (RA) have been proposed. The ACR (American College of Rheumatology--formerly ARA, American Rheumatism Association) remission criteria are strict and include nonspecific symptoms such as fatigue. More recently remission according to the Disease Activity Index (DAS) and DAS28 has been described. However, patients who meet the DAS28 remission cut point of < 2.6 may nonetheless have tender and/or swollen joints. The ACR remission criteria are more rigorous than the requirement of DAS28 <2.6. Newer tools for evaluation of RA activity include the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI), and cut points for remission according to these new indices have been defined. However, all available remission criteria may ignore important aspects of RA, including physical function and radiographic damage.

Järvisalo MJ, Juonala M, Raitakari OT. · The Centre of Applied and Preventive Cardiovascular Medicine, Department of Clinical Physiology, University of Turku, Turku, and Department of Internal Medicine, Satakunta Central Hospital, Pori, Finland. · Curr Opin Clin Nutr Metab Care. · Pubmed #16912549 No free full text.

Abstract: PURPOSE OF REVIEW: To describe the background and assessment of inflammatory markers and endothelial function in atherosclerosis. RECENT FINDINGS: Recent observations have related several inflammation markers, including cytokines and chemokines, soluble adhesion molecules, and acute-phase reactants, to the pathophysiology of atherosclerosis. Chronic inflammatory states such as rheumatoid arthritis and systemic lupus erythematosus have been identified as independent risk factors for early atherosclerosis. The role of endothelial function in atherosclerosis has been elucidated by clinical studies that have demonstrated that the status of vascular endothelium may modify the effects of risk factors on the development of atherosclerosis. These observations support the response-to-injury theory of atherosclerosis that emphasizes the role of endothelium in atherosclerosis. SUMMARY: Inflammation and endothelial function play significant roles in the pathogenesis of atherosclerosis. Elevations in certain inflammatory mediators as well as evidence of endothelial dysfunction are related to increased risk of future cardiovascular morbidity. The value of measuring inflammatory markers and endothelial function in clinical practice remains to be defined.

Roy H, Bhardwaj S, Ylä-Herttuala S. · Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland. · FEBS Lett. · Pubmed #16631753 No free full text.

Abstract: Angiogenesis is the process by which new blood vessels are formed from existing vessels. The vascular endothelial growth factors (VEGFs) are considered as key molecules in the process of angiogenesis. The VEGF family currently includes VEGF-A, -B, -C, -D, -E, -F and placenta growth factor (PlGF), that bind in a distinct pattern to three structurally related receptor tyrosine kinases, denoted VEGF receptor-1, -2, and -3. VEGF-C and VEGF-D also play a crucial role in the process of lymphangiogenesis. Here, we review the biology of VEGFs and evaluate their role in pathological angiogenesis and lymphangiogenesis.

Luosujärvi R. · · Duodecim. · Pubmed #16619890 No free full text.

This publication has no abstract.

Helenius M, Leirisalo-Repo M. · HUS:n kirurgian klinikka, suu- ja leukakirurgian yksikkö. · Duodecim. · Pubmed #16457118 No free full text.

This publication has no abstract.

Nieminen U, Höök-Nikanne J, Kärkkäinen P, Niemelä S. · HUS, sisätaudit, gastroenterologian klinikka. · Duodecim. · Pubmed #16454249 No free full text.

This publication has no abstract.

Kaaja RJ, Greer IA. · Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland. · JAMA. · Pubmed #16333011 links to  free full text

Abstract: CONTEXT: Physiologic changes of pregnancy include insulin resistance, thrombophilia, immunosuppression, and hypervolemia. These changes may herald the development of disease in later life. OBJECTIVE: To summarize current evidence on how pregnancy reveals risk of chronic disease. EVIDENCE ACQUISITION: MEDLINE was searched for articles published between 1990 and 2005 relating pregnancy conditions to the development of chronic disease. Bibliographies and the Web sites of the International Society of Obstetric Medicine and International Society for the Study of Hypertension in Pregnancy were also reviewed. EVIDENCE SYNTHESIS: Pregnancy exaggerates atherogeniclike responses, including insulin resistance and dyslipidemia, manifesting as preeclampsia or gestational diabetes. These complications herald an increased risk of postpartum cardiovascular disease, with a 2-fold increased risk of coronary artery disease and stroke. Women with gestational diabetes mellitus can progress to type 2 diabetes mellitus. The rate of progression varies from 6% to 92% depending on diagnostic criteria, race/ethnicity, and duration of surveillance (from 6 months to 28 years). Pregnancy increases risk of venous thrombosis by 7- to 10-fold. Heritable thrombophilia is present in at least 15% of Western populations and underlies at least 50% of gestational venous thromboses. Thus, the procoagulant changes during pregnancy can unmask hereditary thrombophilia. An important adaptation leading to immunotolerance of the fetoplacental unit is a switch from helper T-cell (T(H)) 1 dominance to T(H)2 dominance. Patients with a T(H)1-dominant immune disease, such as rheumatoid arthritis or multiple sclerosis, improve during pregnancy. However, rheumatoid arthritis is 5 times more likely to develop after delivery than at any other time. During pregnancy, there is a 50% increase in plasma volume, which can unmask glomerulopathies, peripartum cardiomyopathy, arterial aneurysms, or arteriovenous malformations. Development of intrahepatic cholestasis of pregnancy predicts increased risk of later cholelithiasis. CONCLUSIONS: The physiologic changes of pregnancy can reveal risk of chronic diseases. Exaggerated responses reflective of the metabolic syndrome are seen in preeclampsia and gestational diabetes and can herald future cardiovascular and metabolic disease. Pregnancy is therefore an important screening opportunity for cardiovascular and metabolic disease risk factors, with the possibility of early intervention.

Sokka T, Hannonen P, Möttönen T. · Department of Rheumatology, Jyväskylä Central Hospital, Jyväskylä, Finland. · Rheum Dis Clin North Am. · Pubmed #16287594 No free full text.

Abstract: This article reviews the use of conventional disease-modifying antirheumatic drugs (DMARDs) in the treatment of early rheumatoid arthritis (RA). The Finnish early RA cohorts are used as examples of how early and active treatment strategies have improved over time with increasing variety of available DMARDs. Therapy goals of early RA include remission to prevent severe long-term outcomes of RA. Remission can be achieved in a third of patients with early RA using a combination of conventional DMARDs, including methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone. Of patients with early RA, 20% to 30% do not improve enough with conventional treatments and should be identified at early phases to consider institution of biologic agents.

Konttinen YT, Seitsalo S, Lehto M, Santavirta S. · Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. · Acta Orthop. · Pubmed #16263606 links to  free full text

This publication has no abstract.

Isomäki P, Clark JM, Panesar M, Cope AP. · Institute of Medical Technology, Tampere University and Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. · Curr Drug Targets Inflamm Allergy. · Pubmed #16101535 No free full text.

Abstract: Immune and inflammatory responses are governed by antigen-specific T cells, whose activation, differentiation and effector function are induced by signals delivered via the T cell antigen receptor (TCR) and by costimulatory and cytokine receptors. The molecular events leading to the activation of naïve T cells have been extensively studied and are well characterized. Much less is known about the molecular and biochemical events regulating the activation of T cells in chronic inflammatory diseases such as rheumatoid arthritis (RA). This review examines the current state of knowledge of T cell activation in chronic inflammation, focusing on RA, and summarizes experimental data which indicate that the chronic inflammatory process may profoundly affect TCR and cytokine signal transduction pathways. We present evidence suggesting that in chronic inflammation, the antigen-driven TCR-mediated processes are attenuated, while cytokine-driven effector responses are sustained or even enhanced. The possible implications of this inbalance are discussed.