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ID PMID Title PublicationDate abstract
24694497 Autoimmune myelofibrosis accompanied by Sjögren's syndrome in a 47, XXX/46, XX mosaic wom 2014 This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.
21645026 Expression of interleukin-22 in Sjögren's syndrome: significant correlation with disease 2011 Oct Sjögren's syndrome (SS) is an autoimmune disease targeting the exocrine glands resulting in xerostomia/keratoconjunctivitis sicca. Presently, we examined the levels and clinical correlations of IL-22 in SS. Patients with SS together with normal controls were randomly selected. IL-22 was detected at significantly higher levels in sera of patients with SS. The levels of IL-22 present in sera showed statistically significant direct correlations with hyposalivation, anti-SSB, anti-SSA/SSB combined, hypergammaglobulinemia and rheumatoid factor. IL-22 showed a direct correlation with major clinical parameters. The data suggest that IL-22 plays a critical role in the development of SS, and further study is needed to examine its function in human SS.
22898439 Primary biliary cirrhosis in a genetically homogeneous population: disease associations an 2012 Aug 16 BACKGROUND: Primary biliary cirrhosis (PBC) is a disease with genetic and environmental pathogenetic background. Chemicals, infectious agents, hormone therapy, reproductive history and surgical interventions have been implicated in the induction of PBC. Familial PBC has been documented in first degree relatives (FDR). Most cohort studies are genetically heterogeneous. Our study aimed to determine eventual lifestyle or disease associations and familial occurrence rates in a genetically homogeneous and geographically defined population of PBC patients. METHODS: 111 consenting PBC patients, were compared with 115 FDR and 149 controls matched for age, sex, Cretan origin and residence. All participants completed a questionnaire regarding demographics, lifestyle, medical, surgical and reproductive history. Significant variables on the univariate analysis were analyzed by multivariate analysis using a forward step-wise logistic regression model. RESULTS: Dyslipidaemia was found in 69.4% of patients, 60% of FDR and 40.9% of controls (p < 0.0001 and p = 0.003 respectively), autoimmune diseases in 36.9% of patients, 30.4% of FDR and 13.4% of controls (p < 0.0001 and p = 0.011 respectively). Hashimoto's disease (p = 0.003), Raynaud syndrome (p = 0.023) and Sjögren syndrome (p = 0.044) were significantly associated with PBC. On multivariate analysis statistically significant associations were found with primary educational level (AOR 2.304, 95% CI 1.024-5.181), cholecystectomy (AOR 2.927, 95% CI 1.347-6.362) and the presence of at least another autoimmune disease (AOR 3.318, 95% CI 1.177-6.22). Cancer history was more frequent in patients than in controls (p = 0.033). Familial PBC was found to be 9.9%. CONCLUSIONS: Dyslipidaemia and autoimmune diseases were significantly increased not only in patients as expected but also in their FDR. An increased prevalence of malignancies was found in patients. Primary educational level, cholecystectomy and the presence of at least another autoimmune disease were found as putative risk factors for PBC. No association was found with smoking, urinary tract infection or reproductive history. The reported high familial occurrence of PBC could imply screening with AMA of FDR with at least another autoimmune disease.
22018243 Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of pat 2011 INTRODUCTION: In this study, we investigated possible aberrations of monocytes from patients with primary Sjögren's syndrome (pSS). We focused on B-cell-activating factor of the TNF family (BAFF) and IL-6 because they are both produced by monocytes and are known to be involved in the pathogenesis of pSS. METHODS: Peripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-γ, and the amounts of IL-6 and soluble BAFF (sBAFF) produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated. RESULTS: Peripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 than normal monocytes did, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-γ. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes. CONCLUSIONS: The results of the present study suggest that the mechanisms underlying the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is due to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may cause the development of pSS.
22690073 Association between autoimmune pancreatitis and systemic autoimmune diseases. 2012 Jun 7 AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sjögren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.
21844152 Treatment of mucosa-associated lymphoid tissue lymphoma in Sjogren's syndrome: a retrospec 2011 Oct OBJECTIVE: To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjögren's syndrome (SS). METHODS: All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical Center Groningen between January 1997 and January 2009 were analyzed. Clinical course and treatment outcome of SS and MALT lymphoma were evaluated. RESULTS: From a total of 329 patients with SS, 35 MALT-SS patients were identified, with a median followup of 76 months (range 16-153 mo). MALT lymphoma was localized in the parotid gland in all cases. Treatment consisted of "watchful waiting" (n = 10), surgery (n = 3), radiotherapy (n = 1), surgery combined with radiotherapy (n = 2), rituximab only (n = 13), or rituximab combined with chemotherapy (n = 6). Complete response was observed in 14 patients, partial response in 1 patient, and stable disease in 20 patients. In 6 of 7 patients with initially high SS disease activity (M-protein, cryoglobulins, IgM rheumatoid factor > 100 KIU/l, severe extraglandular manifestations), MALT lymphoma progressed and/or SS disease activity increased after a median followup of 39 months (range 4-98 mo), necessitating retreatment. Only 1 patient with MALT who had low SS disease activity showed progression of lymphoma when left untreated. CONCLUSION: An initially high SS disease activity likely constitutes an adverse prognostic factor for progression of lymphoma and/or SS. Such patients may require treatment for both MALT lymphoma and SS. In SS patients with localized asymptomatic MALT lymphoma and low SS disease activity, a "watchful waiting" strategy seems justified.
23256104 Expansion of CD4+CD25-GITR+ regulatory T-cell subset in the peripheral blood of patients w 2012 Dec 11 OBJECTIVES: CD4+CD25high regulatory T cells (TREG) represent a suppressive T cell subset deeply involved in the modulation of immune responses and eventually in the prevention of autoimmunity. Growing evidence demonstrated that patients with autoimmune and inflammatory chronic diseases display an impairment of TREG cells or activated effector T cells unresponsive to TREG. Glucocorticoid-induced TNFR-related protein (GITR) is a widely accepted marker of murine TREG cells, but little is known in humans. Aim of the present study was to investigate the characteristics of different subsets of TREG cells in Sjögren's syndrome and the potential role of GITR as marker of human TREG cells. METHODS: Fifteen patients with primary Sjogren's syndrome (SS) and 10 sex- and age-matched normal controls (NC) were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies. Disease activity was assessed using the EULAR Sjögren's syndrome disease activity index (ESSDAI). RESULTS: Although the proportion of circulating CD25highGITRhigh subset was similar in SS patients and NC, an expansion of the CD25-GITRhigh cell population was observed in the peripheral blood of SS patients. Interestingly, this expansion was more relevant in patients with inactive rather than active disease. CONCLUSIONS: The number of CD4+CD25-GITRhigh cells is increased in SS as compared to NC. Moreover, the fact that the expansion of this cell subset is prevalently observed in patients with inactive disease suggests that these cells may play a role in counteracting inflammatory response.
21669196 Inflammatory myofibroblastic tumor of the lung with unique histological pattern and associ 2011 Oct Inflammatory myofibroblastic tumor (IMT) of the lung is a rare condition. Radiological properties and clinical presentation of this disease can mimic malignant process. We present a case of IMT of the lung in a 58 year old female patient with a single lung nodule. Tumor was unencapsulated, firm, and well circumscribed. Microscopically tumor had multinodular structure with single or multiple small blood vessels in the center of each nodule surrounded in circular pattern by connective tissue containing spindle cells embedded into the thick layers of extracellular matrix. Extracellular matrix was identified as type I and type III collagen fibrils embedded into type IV collagen and laminin. The tumor was surrounded by T-, B-lymphocytes and polyclonal plasma cells. Histological organization of this lesion's stromal component was unique, but cell composition was similar to inflammatory pseudotumor of the lung. In addition, tumor tissue sections exhibited strong positivity for IgG, weak positivity for IgA, 1Cq, but were negative for IgM, and C3. Mutational analysis of the EGFR, KRAS genes and ALK locus rearrangement were performed and did not reveal any mutations. This is the first report of an IMT associated with Sjögren's disease, systemic lupus erythematosus and Non-Hodgkin lymphoma developing in the lungs. Patient was clinically followed up for 18 months and no recurrence of the tumor observed.
21666236 Gene expression profiling of early-phase Sjögren's syndrome in C57BL/6.NOD-Aec1Aec2 mice 2011 Jul 29 PURPOSE: Despite considerable efforts, the molecular and cellular events in lacrimal gland tissues initiating inflammatory responses leading to keratoconjunctivitis sicca (KCS), autoimmunity, and Sjögren's syndrome (SjS) have yet to be defined. To determine whether altered glandular homeostasis occurs before the onset of autoimmunity, a temporal transcriptome study was carried out in an animal model of primary SjS. METHODS: Using oligonucleotide microarrays, gene expression profiles were generated for lacrimal glands of C57BL/6.NOD-Aec1Aec2 mice 4 to 20 weeks of age. Pairwise analyses identified genes differentially expressed, relative to their 4-week expression, during the development of SjS-like disease. Statistical analyses defined differentially and coordinately expressed gene sets. The PANTHER (Protein ANalysis THrough Evolutionary Relationships) classification system was used to define annotated biological processes or functions. RESULTS: Temporal transcript expression profiles of C57BL/6.NOD-Aec1Aec2 lacrimal glands before, or concomitant with, the first appearance of inflammatory cells revealed a highly restricted subset of differentially expressed genes encoding interactive extracellular matrix proteins, fibronectin, integrins, and syndecans. In contrast, genes encoding interepithelial junctional complex proteins defined alterations in tight junctions (TJ), adherens, desmosomes, and gap junctions, suggesting perturbations in the permeability of the paracellular spaces between epithelial barriers. Correlating with this were gene sets defining focal adhesion (FA) maturation and Ras/Raf-Mek/Erk signal transduction. Immunohistochemically, FAs were associated with infiltrating leukocytes and not with lacrimal epithelial cells. CONCLUSIONS: For the first time, FA maturations are implicated as initial biomarkers of impending autoimmunity in lacrimal glands of SjS-prone mice. Changes in TJ complex genes support an increased movement of cells through paracellular spaces.
21149398 Markedly increased IL-18 liver expression in adult-onset Still's disease-related hepatitis 2011 Apr OBJECTIVES: First, to investigate the prevalence of liver involvement in adult-onset Still's disease (AOSD) Italian patients; secondly, to measure serum IL-18 concentration and correlate its level to other inflammatory markers and disease activity; and thirdly to characterize the expression level and the cellular source of IL-18 in the liver of a patient with AOSD with hepatitis. METHODS: The clinical charts of 41 consecutive Italian AOSD patients were evaluated with special attention to liver involvement. Serum levels of IL-18 were measured in 21 patients. Finally, the case of a 33-year-old woman with hepatitis where a liver biopsy was obtained and sections stained with antibodies against IL-18 and CD68 is described in detail. RESULTS: Of the 41 AOSD patients, 32 and 39% displayed increased AST level or ALT level, respectively, generally normalizing with steroid treatment, while 41% had evidence of hepatosplenomegaly. Circulating IL-18 levels were significantly higher in those with active disease compared with 85 controls. A correlation was observed between IL-18 serum level and disease activity, serum ferritin level and neutrophil count. IL-18 concentration was markedly increased in the patient with active hepatitis. Intense IL-18 expression was detected within the liver parenchyma and double staining with IL-18 and CD68 clearly showed colocalization of the cytokine with the macrophage marker. CONCLUSION: Macrophage-derived IL-18 might play a central role in the pathogenesis of AOSD. IL-18 serum level is higher in patients with active AOSD and its local, rather than systemic, expression may be responsible for tissue damage in some target organs, such as liver.
21422651 Clinical features and histological patterns of lupus nephritis in Eastern Nepal. 2011 Mar To determine the clinical profile and patterns of lupus nephritis patients in Eastern Nepal, we studied 38 patients fulfilling the 1982 revised criteria of American College of Rheumatology for systemic lupus erythematous (SLE), followed up from January 2004 to January 2008. Arthritis was a common initial feature in addition to variable cutaneous, cardiac, pulmonary and neuropsychiatric manifestations. Renal biopsy showed grade 1 changes in 5 (13.5%) patients, grade 2 changes in 13 (35.1%) patients, grade 3 changes in 9 (24.3%) patients, grade 4 changes in 7 (18.9%) patients, grade 5 changes in 2 (5.4%) patients, and grade 6 changes in 2.7% patients. Antinuclear antibody (ANA) assay and anti-ds DNA were positive in 78.4 and 81.1%, respectively. We conclude that mesangial proliferative glomerulonephritis (grade 2) was the most common pattern of lupus nephritis encountered in our study. Timely diagnosis and treatment may improve the overall patients' survival.
22566812 A four-step model for the IL-6 amplifier, a regulator of chronic inflammations in tissue-s 2011 It is commonly thought that autoimmune diseases are caused by the breakdown of self-tolerance, which suggests the recognition of specific antigens by autoreactive CD4+ T cells contribute to the specificity of autoimmune diseases (Marrack et al., 2001; Mathis and Benoist, 2004). In several cases, however, even for diseases associated with class II major histocompatibility complex (MHC) alleles, the causative tissue-specific antigens recognized by memory/activated CD4+ T cells have not been established (Mocci et al., 2000; Skapenko et al., 2005). Rheumatoid arthritis (RA) and arthritis in F759 knock-in mice (F759 mice) are such examples (Atsumi et al., 2002; Brennan et al., 2002; Falgarone et al., 2009). These include associations with class II MHC and CD4 molecules; increased numbers of memory/activated CD4+ T cells; and improved outcomes in response to suppressions and/or deficiencies in class II MHC molecules, CD4+ T cells, and the T cell survival cytokine IL-7. Regarding the development of arthritis in F759 mice, it is not only the immune system, but also non-immune tissue that are involved, indicating that the importance of their interactions (Sawa et al., 2006, 2009; Ogura et al., 2008; Hirano, 2010; Murakami et al., 2011). Furthermore, we have shown that local events such as microbleeding together with an accumulation of activated CD4+ T cells in a manner independent of tissue antigen-recognitions induces arthritis in the joints of F759 mice (Murakami et al., 2011). For example, local microbleeding-mediated CCL20 expression induce such an accumulation, causing arthritis development via chronic activation of an IL-17A-dependent IL-6 signaling amplification loop in type 1 collagen+ cells that is triggered by CD4+ T cell-derived cytokine(s) such as IL-17A, which leads to the synergistic activation of STAT3 and NFκB in non-hematopoietic cells in the joint (Murakami et al., 2011). We named this loop the IL-6-mediated inflammation amplifier, or IL-6 amplifier for short (Ogura et al., 2008; Hirano, 2010; Murakami et al., 2011). Thus, certain class II MHC-associated, tissue-specific autoimmune diseases, including some RA subtypes, may be induced by local events that cause an antigen-independent accumulation of effector CD4+ T cells followed by the induction of the IL-6 amplifier in the affected tissue. In other words, in certain cases, the target tissue itself may determine the specificity of the autoimmune disease via activation of the IL-6 amplifier. To explain this hypothesis, we have proposed a four-step model for MHC class II-associated autoimmune diseases (Murakami et al., 2011): (1) T cell activation regardless of antigen specificity; (2) local events inducing a tissue-specific accumulation of activated T cells; (3) transient activation of the IL-6 amplifier; and (4) enhanced sensitivity to cytokines in the target tissue. The interaction of these events results in chronic activation of the IL-6 amplifier and subsequent manifestation of autoimmune diseases. Thus, the IL-6 amplifier, which is chronically activated by these four events, is a critical regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases.
20658239 Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthriti 2012 Jan Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.
23295110 Certolizumab pegol attenuates the pro-inflammatory state in endothelial cells in a manner 2013 Mar OBJECTIVES: Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and premature cardiovascular death. Anti-TNF therapy is thought to reduce clinical cardiovascular disease risk and improve vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to explore the effects of certolizumab pegol (CZP) on TNF-activated human aortic endothelial cells (HAoECs). METHODS: HAoECs were cultured in vitro and exposed to i) TNF alone, ii) TNF plus CZP, or iii) neither agent. Microarray analysis and quantitative polymerase chain reaction were used to analyse gene expression. Activation of NF-κB was investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was performed to detect microparticle release from HAoECs. RESULTS: TNF alone had strong effects on endothelial gene expression, while TNF and CZP together produced a global gene expression pattern similar to untreated controls. In particular, genes for E-selectin, VCAM-1 and ICAM-1 were significantly up-regulated by TNF treatment. Notably, the TNF/CZP cocktail prevented the up-regulation of these genes. TNF-induced nuclear translocation of NF-κB was abolished by treatment with CZP. In addition the increased production of endothelial microparticles in TNF-activated HAoECs was prevented by treatment with CZP. CONCLUSIONS: We have found at cellular level, that a clinically available TNF inhibitor, CZP i) reduces adhesion molecule expression; ii) prevents TNF-induced activation of the NF-κB pathway and iii) prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions.
23212873 Whole-body MRI for inflammatory arthritis and other multifocal rheumatoid diseases. 2012 Nov Whole-body MRI (WBMRI) is an excellent tool for the imaging of rheumatologic diseases with a multifocal and systemic character. These include the different forms of spondyloarthritis, chronic recurrent multifocal osteomyelitis (CRMO), and inflammatory muscle diseases along with diseases such as systemic lupus and systemic sclerosis that show organ involvement. Although it is not recommended as a first-line investigation in every patient, it may add important information in difficult cases. Currently WBMRI for inflammatory arthritis is mainly used in imaging the seronegative spondyloarthropathies. The technique visualizes most of the involved joints and soft tissue structures with both (early) active and chronic inflammatory changes in one examination. Different patterns of joint involvement can be recognized, with both the acute features of the disease and the longer term sequelae being shown. The technique also allows therapeutic response to be assessed. In CRMO, WBMRI is able to detect asymptomatic and radiographically occult multifocal lesions that typically show a symmetrical distribution predominating in the lower extremity. In inflammatory muscle diseases, WBMRI is able to provide important information for biochemical and genetic differential diagnosis because there is growing knowledge of the correlation between typical patterns of disease and defined clinical entities. In addition, it helps in biopsy localization and is very well suited for assessing disease activity. WBMRI is particularly useful for studying internal organ involvement, especially the brain, heart, and lungs in connective tissue diseases such as systemic lupus erythematosus in one whole-body exam.
22035430 MDHAQ/RAPID3 scores: quantitative patient history data in a standardized "scientific" form 2011 Quantitative measurement according to a laboratory test such as hemoglobin A1c or creatinine provides a "gold standard" for care of every individual with a specific diagnosis. By contrast, no single "gold standard" quantitative measure is available in rheumatic diseases. Laboratory tests are limited, and clinical decisions are based more on patient history and physical examination than laboratory tests. A quantitative patient history is provided by a self-report questionnaire as standardized, "scientific" data to compare from one visit to the next. Patient questionnaires for usual clinical care emphasize feasibility, acceptability to patients and physicians, and clinical utility, which are not considered in research questionnaires. Development of a multidimensional health assessment questionnaire (MDHAQ) over 27 years is seen as a continuous quality improvement (CQI) rather than research activity, to account for all rather than a few selected patients for a research study. Both the traditional HAQ and MDHAQ are 2-page questionnaires, easily completed by patients in 5 to 10 minutes, although scoring a HAQ disability index (HAQ-DI) requires 42 seconds, compared to 5 seconds for an MDHAQ/RAPID3. The MDHAQ includes, within 2 pages: complex activities, psychological queries, visual analog scales (VAS) as 21 numbered circles rather than 10-cm lines, a fatigue VAS, RADAI (rheumatoid arthritis disease activity index) self-report joint count, traditional "medical" review of systems and recent medical history, and demographic data, as well as a data management system that incorporates medication data and laboratory tests, reports for physicians and patients, and flow sheets to compare a current visit with a previous visit.
23101232 [Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology] 2012 Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses, Gold Medal for the Merits of the Country Defense, and the 'Auschwitz' Cross. He was also the recipient of the medals: Copernicus (1997) and Gloria Medicinae (2001).
21602177 Specific expression of PAD4 and citrullinated proteins in lung cancer is not associated wi 2011 Jun Anti-citrullinated protein antibodies (ACPAs), produced against citrullinated proteins, are diagnostic and prognostic markers of rheumatoid arthritis (RA). The underlying mechanism that explains the connection of smoking, citrullination [catalyzed by peptidyl arginine deiminases (PADs)] and ACPAs is still unclarified in RA. Thus, we searched for a non-arthritic model in which an increased cell death allows the formation of autoantibodies. Data supporting that lung cancer might be a good candidate are as follows: (i) smoking plays a role in its pathogenesis, (ii) the disease is frequently accompanied by paraneoplastic syndrome, (iii) smoking increases citrullination in the lung, (iv) various types of malignancies are associated with increased citrullination and (v) lung cancer tissue shows similarities with RA synovium. Serum PAD4, rheumatoid factor (RF) and ACPA levels were measured in 42 lung cancer patients; expression of cytokeratin 7 (CK7), PAD4 and citrullinated proteins was visualized in 113 lung cancer tissues. All parameters were analyzed in correlation with smoking history. None of the patients had polyarthritis or autoimmune disease. Significantly increased RF levels were associated with higher PAD4 levels in smoker lung cancer patients compared with non-smokers. Both PAD4 and citrullination immunostaining strongly correlated with that of CK7 in lung cancer, however, did not differ according to smoking history. Two of 30 smoker lung cancer patients had high anti-cyclic citrullinated peptide levels. In conclusion, PAD4 and citrullination may be helpful in distinguishing lung cancer from healthy tissue. Smoking, abnormal serum PAD4 and RF levels may not be sufficient for the production of ACPAs and development of autoimmunity.
19770265 Anti-Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa R 2011 The fruits of Barringtonia racemosa are prescribed in the ayurvedic literature for the treatment of pain, inflammation and rheumatic conditions. In present investigation, activity guided isolation of bartogenic acid (BA) and its evaluation in the Complete Freund's Adjuvant (CFA)-induced arthritis in rats is reported. Among the various extracts and fractions investigated preliminarily for carrageenan-induced acute inflammation in rats, the ethyl acetate fraction displayed potent anti-inflammatory activity. Large-scale isolation and characterization using chromatography and spectral study confirmed that the constituent responsible for the observed pharmacological effects was BA. Subsequently the BA was evaluated for effectiveness against CFA-induced arthritis in rats. The results indicate that at doses of 2, 5, and 10 mg kg(-1) day(-1), p.o., BA protects rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations induced by CFA. The serum markers of inflammation and arthritis, such as C-reactive protein and rheumatoid factor, were also reduced in the BA-treated arthritic rats. The overall severity of arthritis as determined by radiological analysis and pain scores indicated that BA exerts a potent protective effect against adjuvant-induced arthritis in rats. In conclusion, the present study validates the ethnomedicinal use of fruits of B. racemosa in the treatment of pain and inflammatory conditions. It further establishes the potent anti-arthritic effects of BA. However, additional clinical investigations are needed to prove the efficacy of BA in the treatment of various immuno-inflammatory disorders.
21636626 Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus 2011 Aug OBJECTIVE: To evaluate the prevalence of chronic polyarthritis in juvenile systemic lupus erythematosus (JSLE) and to describe the manifestations, treatments, and outcomes in these patients. METHODS: From January 1983 to July 2010, 5419 patients were followed up at the Pediatric Rheumatology Unit of the University Hospital and 271 (5%) of them had JSLE (American College of Rheumatology [ACR] criteria). 'Rhupus' was classified as the overlap of juvenile idiopathic arthritis (International League of Associations for Rheumatology [ILAR] criteria) and JSLE. We evaluated demographic data, polyarthritis and other clinical manifestations, disease activity and damage, laboratory exams, radiographic findings, treatments, and outcomes. RESULTS: The prevalence of chronic polyarthritis in this JSLE population was 2.6% (7/271). This articular involvement was the initial manifestation in all seven JSLE patients. The median duration of chronic polyarthritis was 11 months (range 2-15 months). Interestingly, rhupus with chronic polyarthritis and limitation of movement, presence of rheumatoid factor, autoantibodies, and/or radiographic abnormalities (juxtaarticular osteopenia, joint-space narrowing, or erosions) was evidenced in three patients. No patient had deformities of hands and feet associated with Jaccoud's arthropathy or osteonecrosis. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, naproxen 10-15 mg/kg/day) when polyarthritis diagnosis was established. Prednisone and antimalarials were administered at JSLE diagnosis. The three non-responsive rhupus patients were treated in conjunction with immunosuppressive drugs (methotrexate, azathioprine, and/or cyclosporine). CONCLUSIONS: Chronic polyarthritis was a rare lupus manifestation in active pediatric patients. The interesting overlap between chronic arthritis and lupus, called rhupus suggests a new entity with a different clinical profile and a poor response to treatment with NSAIDs alone. In addition, the occurrence of this association in JSLE patients could be classified as a clinical sub-group of JSLE with possible specific genetic determinants.