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ID PMID Title PublicationDate abstract
22541742 An improved approach to diagnosing and treating conjunctival mucoepidermoid carcinoma. 2012 Jul The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.
22472783 A short story of anti-rheumatic therapy. VIII. The immunodepressants. 2012 Mar 19 The use of immunosuppressive drugs in rheumatology is fairly recent, starting just after the Second World War with the introduction of the first alkylating agents in oncohematology. When it became clear that some rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus, showed an immune-mediated pathogenesis, including proliferation of immunocompetent cells, an application was soon found for immunosuppressive drugs in their treatment. This review outlines the historical milestones that led to the current use of drugs belonging to the major groups of immunosuppressants, i.e. alkylating agents (cyclophosphamide), folic acid (methotrexate) and purine (azathioprine) antagonists. We will also talk about the history of cyclosporin A, the first "selective" immunosuppressive agent, and that of some immunoactive drugs used more recently in rheumatology, such as mycophenolate mofetil, dapson and thalidomide, is briefly described.
22414700 The triad of success in personalised medicine: pharmacogenomics, biotechnology and regulat 2012 Sep 15 The population of the world has recently passed the 7 billion milestone and as the cost of human genome sequencing is rapidly declining, sequence data of billions of people should be accessible much sooner than anyone would have predicted 10 years ago. This will form the basis of personalised medicine. However it is still not clear, even in principle, whether these data, combined with data of the expression of one's genome in various cells and tissues relevant to different diseases, could be used effectively in clinical medicine and healthcare, or in predicting responses to different therapies. Therefore this is an important issue which needs to be addressed before more resources are wasted on less than informative studies and surveys simply because technologies exist. As a typical example, we have selected and summarise here key studies from the biomedical literature that focus on gene expression profiling of the response to biologic therapies in peripheral blood and biopsy samples in autoimmune diseases such as rheumatoid arthritis, spondylarthropathy, inflammatory bowel diseases and psoriasis. We also present the state of the biotechnology market from a European perspective, discuss how spin-offs leverage the power of genomic technologies and describe how they might contribute to personalised medicine. As ethical, legal and social issues are essential in the area of genomics, we analysed these aspects and present here the European situation with a special focus on Hungary. We propose that the synergy of these three issues: pharmacogenomics, biotechnology and regulatory issues should be considered a triad necessary to succeed in personalised medicine.
22364132 Inflammation-induced thrombosis: mechanisms, disease associations and management. 2012 Although inflammation-induced thrombosis is a well-known entity, its pathogenesis remains complicated. There are complex interactions between inflammation and hemostasis, involving proinflammatory cytokines, chemokines, adhesion molecules, tissue factor expression, platelet and endothelial activation, and microparticles. Inflammation increases procoagulant factors, and also inhibits natural anticoagulant pathways and fibrinolytic activity, causing a thrombotic tendency. Besides, chronic inflammation may cause endothelial damage, resulting in the loss of physiologic anticoagulant, antiaggregant and vasodilatory properties of endothelium. However, inflammation- induced venous thrombosis may develop even in the absence of vessel wall damage. On the other hand, coagulation also augments inflammation, causing a vicious cycle. This is mainly achieved by means of thrombin-induced secretion of proinflammatory cytokines and growth factors. Platelets may also trigger inflammation by activating the dendritic cells. There are many systemic inflammatory diseases characterized by thrombotic tendency, including Behçet disease (BD), antineutrophilic cytoplasmic antibody-associated vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus, antiphosholipid syndrome, familial Mediterranean fever, thromboangiitis obliterans (TAO) and inflammatory bowel diseases. Inflammation-induced thrombosis may respond to immunosuppressive (IS) treatment, as in the case of BD. However effectiveness of this treatment can not be generalized to all other inflammatory diseases. For instance, IS agents do not have any beneficial role in the management of TAO. Heparin, antiplatelet agents such as aspirin and clopidogrel, colchicine and statins also have some antiinflammatory activity. However, decreased responsiveness to aspirin and clopidogrel treatments may be observed in inflammatory diseases, due to antiplatelet resistance caused by systemic inflammation. In the present review, we aimed to discuss the details of the complex crosstalk between inflammation and hemostasis in the context of available data. We also intended to overview the major inflammatory diseases with thrombotic tendency, as well as to discuss the general principles of the management of inflammation-induced thrombosis.
22286648 The role of the HLA-G gene and molecule on the clinical expression of rheumatologic diseas 2012 Jan Human leukocyte antigen G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by low polymorphism in its coding region, a limited tissue distribution pattern in physiologic conditions, and expression through soluble isoforms and isoforms bound to surface membranes through alternative splicing. HLA-G is fairly known since it is involved in induction and maintenance of tolerance between the maternal immunologic system and the semi-allogeneic fetus at the level of the fetal-placental interface. Besides, several studies have indicated a wider immunoregulatory role of this molecule. In this context, the expression of HLA-G in inflammatory and rheumatologic diseases is a relatively recent research area. The first studies described the expression of HLA-G in several inflammatory myopathies, atopic dermatitis, and cutaneous psoriasis. Based on the findings that HLA-G could divert T helper responses to the Th2 type, it was hypothesized that HLA-G would be a protective molecule in inflammatory responses. In this article, we review the potential roles of the HLA-G molecule in the immune system and in several rheumatologic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and others.
22202096 Integrating structure and function of 'tandem-repeat' galectins. 2012 Jan 1 Galectins (GALs) are evolutionarily-conserved lectins defined by at least one carbohydrate recognition domain (CRD) with affinity for beta-galactosides and conserved sequence motifs. Although the biological roles of some members of this family, including the 'proto-type' GAL-1 and the 'chimera-type' GAL-3 have been widely studied, the functions of 'tandem-repeat' galectins are just emerging. The subgroup of 'tandem-repeat' galectins (GAL-4, -6, -8, -9, and -12) contain two distinct CRDs, connected by a linker peptide. Here we integrated and distilled the available information on 'tandem-repeat' galectins, their specific structures, potential ligands and biological activities in inflammatory and neoplastic diseases. While GAL-4 has been implicated in inflammatory bowel diseases, either as a pro-inflammatory or pro-apoptotic mediator, GAL-8 plays roles in autoimmune diseases such as rheumatoid arthritis and lupus erythematosus and modulates tumor progression. GAL-9 controls allergic inflammation and Th1/Th17-mediated autoimmunity and has prognostic value in certain tumor types. Finally, GAL-12 plays important roles in adipocyte physiology. Although this information is just emerging, further studies are needed to dissect the biological roles of 'tandem-repeat' galectins in health and disease.
22079211 The importance of patient-centered care for various patient groups. 2013 Mar OBJECTIVES: To assess differences in the importance ascribed to patient-centered care between various patient groups and demographic groups. METHODS: Survey data collected using questionnaires were analyzed for patients that underwent hip or knee surgery (n=214), patients suffering from rheumatoid arthritis (n=343), spinal disk herniation (n=145), breast abnormalities (n=596) or congestive heart failure (n=118). A composite for patient-centered care priorities was constructed (α=0.82) and compared to the average importance over all healthcare aspects in the surveys. RESULTS: All patient groups considered patient-centered care to be of above-average importance (p's<0.001). Small but significant differences were observed: patient-centered care was more important for patients suffering from congestive heart failure (p<0.001) and patients who were younger, female, well-educated and healthier (p's<0.05). Patients who had undergone hip or knee surgery considered patient-centered care more important than patients with spinal disk herniation did (p<0.05). CONCLUSION: Patient-centered care is important to all patient groups. Differential policies regarding patient-centered care for patient subgroups do not seem required. PRACTICAL IMPLICATIONS: Given the importance attributed to patient-centered care, it is essential that elements of patient-centered care are included in surveys, indicators of quality of care, and the training of doctors and nurses.
22021089 A clinically applicable six-segmented foot model. 2012 Apr We describe a multi-segmented foot model comprising lower leg, rearfoot, midfoot, lateral forefoot, medial forefoot, and hallux for routine use in a clinical setting. The Ghent Foot Model describes the kinematic patterns of functional units of the foot, especially the midfoot, to investigate patient populations where midfoot deformation or dysfunction is an important feature, for example, rheumatoid arthritis patients. Data were obtained from surface markers by a 6 camera motion capture system at 500 Hz. Ten healthy subjects walked barefoot along a 12 m walkway at self-selected speed. Joint angles (rearfoot to shank, midfoot to rearfoot, lateral and medial forefoot to midfoot, and hallux to medial forefoot) in the sagittal, frontal, and transverse plane are reported according to anatomically based reference frames. These angles were calculated and reported during the foot rollover phases in stance, detected by synchronized plantar pressure measurements. Repeated measurements of each subject revealed low intra-subject variability, varying between 0.7° and 2.3° for the minimum values, between 0.5° and 2.1° for the maximum values, and between 0.8° and 5.8° for the ROM. The described movement patterns were repeatable and consistent with biomechanical and clinical knowledge. As such, the Ghent Foot model permits intersegment, in vivo motion measurement of the foot, which is crucial for both clinical and research applications.
21984128 Serum IgG levels demonstrate seasonal change in connective tissue diseases: a large-scale, 2012 Jun Hypergammaglobulinemia is often found in patients with autoimmune diseases, such as systemic lupus erythematosus (SLE), and its level may correlate with disease activity. However, it is unclear whether immunoglobulin G (IgG) displays seasonal changes. We analyzed the seasonal change in serum IgG by assessing 450 patients with connective tissue disease. The serum IgG levels in summer were compared with those in winter from 2006 to 2009. Independent samples from 355 patients were analyzed to confirm results in the first set. The differences in the IgG levels between the two seasons were analyzed in each disease and compared with disease activity. 488 patients without connective tissue disease were analyzed as reference instead of healthy people as control. We found that connective tissue disease patients tended to show higher levels of serum IgG in summer than in winter every year from 2006 to 2009, whereas patients without connective tissue disease did not demonstrate such a tendency. We observed this seasonal tendency in each disease. Seasonal changes weakly correlated with those of anti-DNA antibody in SLE patients and those of disease activity score in rheumatoid arthritis (RA) patients. Serum IgG levels of patients with connective tissue diseases display seasonal variations. Biological and clinical significance of these variations should be elucidated.
21953776 The binding mode of cladocoran A to the human group IIA phospholipase A(2). 2011 Nov 25 The molecular basis for human group IIA phospholipase A(2) inactivation by the marine natural product cladocoran A (CLD A) has been studied in order to elucidate its relevant anti-inflammatory properties. Indeed, secretory phospholipases A(2) are well-known to be implicated in the pathogenesis of inflammation, such as rheumatoid arthritis, septic shock, psoriasis and asthma, thus the understanding of their inactivation mechanism could be useful for the development of new chemical classes of selective inhibitors. Our results, collected by a combination of biochemical approaches, advanced mass spectrometry and molecular modeling, suggest a competitive inhibition mechanism guided by a noncovalent molecular recognition event, and disclose the key role of the CLD A γ-hydroxybutenolide ring in the chelation of the catalytic calcium ion inside the enzyme active site. Moreover, CLD A is able to react selectively with Ser82, although this covalent event seems to play a secondary role in terms of enzyme inhibition.
21826374 Selective IgA deficiency in autoimmune diseases. 2011 Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.
21824857 [Evaluation of fracture risk in osteoporosis]. 2011 Aug 14 Osteoporotic fractures are associated with excess mortality. Effective treatment options are available, which reduce the risk of vertebral and non-vertebral fractures, but the identification of patients with high fracture risk is problematic. Low bone mineral density (BMD)--the basis for the diagnosis of osteoporosis--is an important, but not the only determinant of fracture risk. Several clinical risk factors are know that operate partially or completely independently of BMD, and affect the fracture risk. These include age, a prior fragility fracture, a parental history of hip fracture, use of corticosteroids, excess alcohol intake, rheumatoid arthritis, and different types of diseases which can cause secondary bone loss. The FRAX® tool integrates the weight of above mentioned clinical risk factors for fracture risk assessment with or without BMD value, and calculates the 10-year absolute risk of hip and major osteoporotic (hip, vertebral, humerus and forearm together) fracture probabilities. Although the use of data is not yet uniform, the FRAX® is a promising opportunity to identify individuals with high fracture risk. The accumulation of experience with FRAX® is going on and it can modify current diagnostic and therapeutic recommendations in Hungary as well.
21807112 Understanding uveitis: the impact of research on visual outcomes. 2011 Nov The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age. Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects. The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved.
21778811 Generalized vitiligo and associated autoimmune diseases in Japanese patients and their fam 2011 Dec BACKGROUND: Generalized vitiligo is an acquired disorder in which depigmented macules result from the autoimmune loss of melanocytes from the involved regions of skin. Generalized vitiligo is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease), rheumatoid arthritis, adult-onset type 1 diabetes mellitus, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison's disease. METHODS: One hundred and thirty-three Japanese patients with generalized vitiligo were enrolled in this study to investigate the occurrence of autoimmune diseases in Japanese patients with generalized vitiligo and their families. RESULTS: Twenty-seven of the patients with generalized vitiligo (20.3%) had autoimmune diseases, particularly autoimmune thyroid disease (sixteen patients, 12%) and alopecia areata (seven patients, 5.3%). Thirty-five patients (26.3%) had a family history of generalized vitiligo and/or other autoimmune diseases. Familial generalized vitiligo was present in fifteen (11.3%), including four families with members affected by autoimmune disorders. Twenty (15.0%) had one or more family members with only autoimmune disorders. CONCLUSIONS: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.
21735740 [Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias]. 2011 Jun To clarify the effects of anticoagulant therapy, we investigated patients with rapidly progressive interstitial pneumonias, retrospectively. We defined rapidly progressive pneumonia as idiopathic or secondary interstitial pneumonia with acute exacerbation of respiratory symptoms within 2 months, without infection or heart failure. A total of 20 cases admitted to our hospital between April 1999 and January 2010 met our criteria. Of those 20 cases, 6 were non-idiopathic pulmonary fibrosis (non-IPF), 3 were IPF, 6 were amyopathic dermatomyositis (ADM), 2 were DM, 2 were rheumatoid arthritis, and 1 was mixed connective-tissue disease. We divided the 20 cases into two groups according to whether they were treated with anticoagulant therapy (dalteparin and/or warfarin) (group A, n = 11) or not (group B, n = 9), and compared their outcomes. They were all given standard therapy. There was significantly better survival time in group A than in group B by the Kaplan-Meier survival curve (p = 0.0389). Anticoagulant therapy may improve the survival of patients with rapidly progressive interstitial pneumonias.
21562019 Coping with health-stressors and defence styles associated with health-related quality of 2011 Aug This study aimed to assess the association of coping with health-stressors and defence styles with health-related quality of life (HRQOL) in systemic lupus erythematosus (SLE). In 56 SLE patients we assessed disease activity (SLEDAI), functional limitations (HAQ), psychological distress (SCL-90-R), defence styles (Defence Style Questionnaire), hostility (HDHQ), coping with health-stressors (Sense of Coherence scale) and HRQOL (WHOQOL-BREF). Two hundred and eight rheumatologic patients (168 with rheumatoid arthritis [RA] and 40 with primary Sjögren's syndrome [SS]) served as disease controls. SLE patients' HRQOL was similar to that of patients with RA and primary SS after adjusting for demographic and disease variables. Psychological distress was significantly associated with most aspects of HRQOL, but sense of coherence mediated the relationship of psychological distress with Physical HRQOL; this mediation effect was unique to SLE, as mediation analyses showed. Maladaptive action defence style was also significantly associated with Environment HRQOL independently of psychological distress (p < 0.024). These findings indicate that, apart from the early assessment and treatment of psychological distress, clinicians and consultation-liaison psychiatrists should bear in mind the SLE patients' psychological resources and coping capacities to deal with the stress of the disease, since such traits, although usually underestimated, are strongly independently associated with HRQOL.
21329560 Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apo 2011 Jan Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.
21526358 Polyarticular lipoma arborescens--a clinical and aesthetical case. 2013 Jun Lipoma arborescens is a benign tumor, but it may be a reactive process to other disorders, and its clinical, analytical, radiological and ultrasound presentation may be redundant to any synovial tumor. Despite the characteristic feature on magnetic resonance imaging (MRI), the correct differential diagnosis in atypical presentation, and the need for timely removal of the lesion to prevent joint damage, forces, ultimately, to invasive procedures. The clinical case reported here, fourth described in English language publications on the polyarticular form, also presented other specificities related to one of the swellings, in the knee. Because of its atypical location in the popliteal fossa, recurrent episodes of joint effusion, personal history of knee trauma, pulmonary tuberculosis, and family history of rheumatoid arthritis required particular attention. This process was hampered by the refusal of knee (and ankle) surgery by the patient. He accepted surgical removal of the swellings of the wrists, for aesthetical reasons, with pathologic confirmation of the diagnosis, and clinical success in that location. MRI of the knee showed the typical image of lipoma arborescens, but also other changes that compromise the prognosis.
21428825 MIF as a disease target: ISO-1 as a proof-of-concept therapeutic. 2011 Jan Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that has been implicated as playing a causative role in many disease states, including sepsis, pneumonia, diabetes, rheumatoid arthritis, inflammatory bowel disease, psoriasis and cancer. To inhibit the enzymatic and biologic activities of MIF, we and others have developed small-molecule MIF inhibitors. Most MIF inhibitors bind within the hydrophobic pocket that contains highly conserved amino acids known to be essential for MIF's proinflammatory activity. The best characterized of these small-molecule MIF inhibitors, (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) has been validated in scores of laboratories worldwide. Like neutralizing anti-MIF antibodies, ISO-1 significantly improves survival and reduces disease progression and/or severity in multiple murine models where MIF is implicated. This MIF inhibitor, its derivatives and other MIF-targeted compounds show great promise for future testing in disease states where increased MIF activity has been discovered.
21284531 Risk of asthma and autoimmune diseases and related conditions in patients hospitalized for 2012 May BACKGROUND: Although there are putative mechanistic links between obesity and autoimmune diseases, obesity is not considered a risk factor for most autoimmune diseases. METHODS: Using the nation-wide Hospital Discharge Register we defined a cohort of 29,665 patients hospitalized for obesity since year 1964. The patients were followed for hospitalization for any of 34 autoimmune or related conditions through year 2007. Standardized incidence ratios (SIRs) were calculated for autoimmune diseases in obese individuals compared to those who had not been hospitalized for obesity. RESULTS: Among 22 immune diseases diagnosed after hospitalization for obesity and in at least 5 patients, the overall SIR was 2.05. Of the individual diseases studied, the risk of 16 was significantly increased; none displayed a decreased risk. Psoriasis (4.54) and Behçet's disease (4.49) exhibited the highest risks, followed by Hashimoto's disease/hypothyroidism (4.12) and asthma (3.39). Small but significant increases in SIRs were also noted for the common autoimmune diseases Graves's disease/hyperthyroidism (1.28) and rheumatoid arthritis (1.37). CONCLUSIONS: The present population of obese individuals, subsequently diagnosed with a number of autoimmune diseases and related conditions, was hospitalized at a relatively young age. Further studies are needed to describe the morbidity in the obese population at large.