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ID PMID Title PublicationDate abstract
25491303 Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen an 2014 Dec 10 BACKGROUND: Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon β (IFN-β) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-β on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. METHODS: The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-β was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-β expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-β on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-β. RESULTS: The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-β intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-β in the joint bones was decreased. After IFN-β administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-β directly inhibited RANKL-induced osteoclastogenesis. CONCLUSIONS: Exogenous IFN-β administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-β intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-β expression.
23223420 The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systema 2013 Dec BACKGROUND: Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. OBJECTIVE: To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. DATA SOURCES: PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). STUDY SELECTION: Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). DATA EXTRACTION: Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. DATA SYNTHESIS: Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): <74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). CONCLUSIONS: ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.
23453632 Enhanced apoptosis by disruption of the STAT3-IκB-ζ signaling pathway in epithelial cell 2013 Mar 21 Sjögren's syndrome (SS) is an autoimmune disease characterized by exocrinopathy that leads to dry eye and mouth. Although lymphocyte infiltration into exocrine glands and the generation of autoantibodies have been reported in SS, its pathogenic mechanism remains elusive. Here, we show that mice lacking the transcriptional regulator IκB-ζ developed SS-like inflammation characterized by lymphocyte-infiltrated dacryoadenitis and SS-associated autoantibodies. In particular, epithelial cells, but not hematopoietic cells, lacking IκB-ζ were essential for the development of inflammation. IκB-ζ-deficient epithelial cells in the lacrimal glands exhibited enhanced apoptosis even in the absence of lymphocytes. Administration of caspase inhibitors ameliorated the inflammation, indicating the critical role of caspase-mediated apoptosis. Furthermore, epithelial cell-specific STAT3-deficient mice developed SS-like inflammation with impaired IκB-ζ expression in the lacrimal glands. Thus, this study reveals a pathogenic mechanism of SS in which dysfunction of epithelial cells caused by disruption of STAT3-mediated IκB-ζ induction elicits the activation of self-reactive lymphocytes.
24117612 Upregulation of membrane-bound CD40L on CD4+ T cells in women with primary Sjögren's synd 2014 Jan Epigenetic deregulation of genes encoded on the X chromosome as reported for CD40L in lupus could explain the female predominance of autoimmune diseases. We compared CD40L expression on CD4(+) T cells from primary Sjögren's syndrome (pSS) women and healthy controls and investigated DNA methylation patterns of the promoter and enhancer regions of CD40L. The expression of CD40L on activated CD4(+) T cells was higher in patients with pSS than controls after phorbolmyristate acetate and ionomycin activation (P = 0.02). CD40L mRNA level in CD4(+) T cells did not differ between patients with pSS and controls and was similar in both groups in cultures treated with the demethylating agent 5-azacytidine C. Pyrosequencing analysis revealed no significant differences in methylation profiles between patients and controls. Inducible membrane-bound CD40L on CD4(+) T cells is increased in patients with pSS but was not related to epigenetic deregulation by demethylation patterns of the regulatory regions of CD40L.
24187099 Risk markers of juvenile idiopathic arthritis-associated uveitis in the Childhood Arthriti 2013 Dec OBJECTIVE: To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and non-Hispanic white (NHW) children. METHODS: There were 4983 children with JIA enrolled in the CARRA Registry. Of those, 3967 NHW and AA children were included in this study. Demographic and disease-related data were collected from diagnosis to enrollment. Children with JIA were compared to those with JIA-U. Children with JIA-U were also compared by race. RESULTS: There were 459/3967 children (11.6%) with JIA-U in our cohort with a mean age (SD) of 11.4 years (± 4.5) at enrollment. Compared to children with JIA, they were younger at arthritis onset, more likely to be female, had < 5 joints involved, had oligoarticular JIA, and were antinuclear antibody (ANA)-positive, rheumatoid factor (RF)-negative, and anticitrullinated protein antibody-negative. Predictors of uveitis development included female sex, early age of arthritis onset, and oligoarticular JIA. Polyarticular RF-positive JIA subtype was protective. Nearly 3% of children with JIA-U were AA. However, of the 220 AA children with JIA, 6% had uveitis; in contrast, 12% of the 3721 NHW children with JIA had uveitis. CONCLUSION: In the CARRA registry, the prevalence of JIA-U in AA and NHW children is 11.6%. We confirmed known uveitis risk markers (ANA positivity, younger age at arthritis onset, and oligoarticular JIA). We describe a decreased likelihood of uveitis in AA children and recommend further exploration of race as a risk factor in a larger population of AA children.
24313919 Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully trea 2016 A 38-year-old woman with relapsing longitudinal extensive transverse myelitis and Sjogren's syndrome (SS) was admitted with lower extremity muscle weakness. Studies showed high serum titer of anti-aquaporin4 antibody and gadolinium-enhanced-MRI T1-weighted lesions within thoracic cord. Clinical findings suggested neuromyelitis optica-spectrum disorder (NMO-SD). High-dose corticosteroids, plasma exchange and cyclophosphamide were not effective. After starting tocilizumab, her neurological findings gradually improved. This report describes the first evidence to show tocilizumab could be effective for NMO-SD with SS.
22526828 HTLV-I virological and histopathological analysis in two cases of anti-centromere-antibody 2013 Jan INTRODUCTION: The aim of this study was to show the clinical and pathological characteristics of anti-centromere-antibody (ACA)-seropositive Sjögren's syndrome (SS) in two anti-human T-cell leukemia virus type I (HTLV-I)-seropositive patients. METHODS: One patient was an HTLV-I carrier whereas the other was diagnosed with HTLV-I-associated myelopathy (HAM). Background data including serum HTLV-I titers, viral loads, and cytokine profiles were recorded. Azocarmine with aniline blue (Azan)-Mallory staining and immunohistochemistry of the labial salivary glands (LSGs) and a muscle biopsy specimen from the HAM patient were performed. RESULTS: Serum transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and HTLV-I viral load were high in the HAM-SS patient compared with the HTLV-I carrier. Fibrous change in LSG was prominent in the HAM-SS patient. Although TGF-β expression was similar in the two patients, expression of HTLV-I-related proteins including p12, p28, group-specific antigen (GAG), and nuclear factor kappa-B (NF-κB) in the LSG were dominantly detected in the HAM-SS patient. Frequency of TGF-β staining in HTLV-I-seropositive SS patients without ACA, HTLV-I-seronegative SS patients with ACA, and HTLV-I-seronegative SS patients without ACA was lower than that of the previous two patients. CONCLUSION: A high HTLV-I viral load in situ is supposed to promote the production of cytokines, especially TGF-β, resulting in the fibrous change of LSG in ACA-seropositive SS patients.
23536866 Norisoboldine suppresses osteoclast differentiation through preventing the accumulation of 2013 Norisoboldine (NOR) is the main alkaloid constituent in the dry root of Lindera aggregata (Sims) Kosterm. (L. strychnifolia Vill.). As reported previously, orally administered NOR displayed a robust inhibition of joint bone destruction present in both mouse collagen-induced arthritis and rat adjuvant-induced arthritis with lower efficacious doses than that required for ameliorating systemic inflammation. This attracted us to assess the effects of NOR on differentiation and function of osteoclasts, primary effector cells for inflammatory bone destruction, to get insight into its anti-rheumatoid arthritis mechanisms. Both RAW264.7 cells and mouse bone marrow-derived macrophages (BMMs) were stimulated with RANKL (100 ng/mL) to establish osteoclast differentiation models. ELISA, RT-PCR, gelatin zymography, western blotting, immunoprecipitation and EMSA were used to reveal related signalling pathways. NOR (10 and 30 µM), without significant cytotoxicity, showed significant reduction of the number of osteoclasts and the resorption pit areas, and it targeted osteoclast differentiation at the early stage. In conjunction with the anti-resorption effect of NOR, mRNA levels of cathepsin K and MMP-9 were decreased, and the activity of MMP-9 was attenuated. Furthermore, our mechanistic studies indicated that NOR obviously suppressed the ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of ERK and p38 MAPK, and reduced the nuclear translocation of NF-κB-p65 and DNA-binding activity of NF-κB. However, NOR had little effect on expressions of TRAF6 or the phosphorylation and degradation of IκBα. Moreover, NOR markedly inhibited expressions of transcription factor NFATc1, but not c-Fos. Intriguingly, the subsequent nuclear translocations of c-Fos and NFATc1 were substantially down-regulated. Hence, we demonstrated for the first time that preventing the differentiation and function of osteoclasts at the early stage was an important anti-bone destruction mechanism of NOR, which might be attributed to inhibition of ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of MAPKs/NF-κB/c-Fos/NFATc1 pathways.
24334641 A longterm prospective real-life experience with leflunomide in juvenile idiopathic arthri 2014 Feb OBJECTIVE: To describe a clinical practice with leflunomide (LEF) in juvenile idiopathic arthritis (JIA). METHODS: Patients with JIA seen between May 2008 and May 2012 and considered nonresponsive to methotrexate (MTX) were given LEF and prospectively followed. Primary outcome was a 28-joint Disease Activity Score (DAS28) of low disease activity (< 3.2) in less than 6 months. Childhood Health Assessment Questionnaire (CHAQ) scores and safety data were recorded. RESULTS: Forty-three patients (33 female) were included with 25 (58.1%) polyarticular, 10 oligoarticular (7 extended; 3 persistent), 6 systemic, and 2 enthesitis-related. Ten (23.2%) were rheumatoid factor-positive and 7 (16.3%) had antinuclear antibodies. Prior drugs other than MTX: 11 (25.5%) chloroquine diphosphate + MTX and 2 (4.6%) sulfasalazine + MTX; mean prednisone dose was 6.4 ± 9.3 mg. The MTX dose prior to LEF was 14.5 ± 4.5 mg/m(2)/week. LEF dose and duration of therapy were 16.6 ± 5.2 mg/d and 3.6 ± 2.2 years, respectively. Nineteen patients (44.2%) interrupted LEF: 1 entered remission, 11 were nonresponsive, and 7 were intolerant (16.2%). Baseline DAS28 (5.57 ± 0.7) dropped to 3.7 ± 1.2 at final analysis (p < 0.001) and 16 patients (37.2%) had a low DAS28 [< 3.2; 12 (27.9%) while taking LEF + MTX and 4 (9.3%) while taking monotherapy]. At last followup, the number of patients with DAS28 > 5.1 dropped from 34 (79%) to 9 (20.9%) and CHAQ scores from 0.86 ± 0.7 to 0.44 ± 0.5 (p < 0.001). CONCLUSION: LEF isolated or combined with MTX is effective and safe to treat JIA in patients refractory to MTX.
23365204 Outer surface protein C peptide derived from Borrelia burgdorferi sensu stricto as a targe 2013 Apr Current serodiagnostic assays for Lyme disease are inadequate at detecting early infection due to poor sensitivity and nonspecificity that arise from the use of whole bacteria or bacterial proteins as assay targets; both targets contain epitopes that are cross-reactive with epitopes found in antigens of other bacterial species. Tests utilizing peptides that contain individual epitopes highly specific for Borrelia burgdorferi as diagnostic targets are an attractive alternative to current assays. Using an overlapping peptide library, we mapped linear epitopes in OspC, a critical virulence factor of B. burgdorferi required for mammalian infection, and confirmed the results by enzyme-linked immunosorbent assay (ELISA). We identified a highly conserved 20-amino-acid peptide epitope, OspC1. Via ELISA, OspC1 detected specific IgM and/or IgG in 60 of 98 serum samples (62.1%) obtained from patients with erythema migrans (early Lyme disease) at the time of their initial presentation. By comparison, the commercially available OspC peptide PepC10 detected antibody in only 48 of 98 serum samples (49.0%). In addition, OspC1 generated fewer false-positive results among negative healthy and diseased (rheumatoid arthritis and positive Rapid Plasma Reagin [RPR+] test result) control populations than did PepC10. Both highly specific and more sensitive than currently available OspC peptides, OspC1 could have value as a component of a multipeptide Lyme disease serological assay with significantly improved capabilities for the diagnosis of early infection.
24820632 Tartrate-resistant acid phosphatase 5a in sarcoidosis: further evidence for a novel macrop 2014 Jun BACKGROUND/PURPOSE: Tartrate-resistant acid phosphatase (TRACP) 5a is expressed strongly in inflammatory macrophages (MΦ). Serum TRACP5a is elevated in rheumatoid arthritis patients with extra-articular manifestations of rheumatoid nodules, in a percentage of patients with end-stage chronic kidney disease, and may be a risk marker for acute myocardial infarction. This proof-of-concept study was undertaken in patients with sarcoidosis to further substantiate our hypothesis that TRACP5a protein is a biomarker for macrophages in other chronic inflammatory diseases. METHODS: Immunohistochemical staining for TRACP5a and CD68 was performed in tissues of 19 patients with sarcoidosis. We also measured circulating TRACP5a protein and other inflammation biomarkers including interkeukin-6, angiotensin-converting enzyme, and C-reactive protein in 13 patients. Twenty healthy age-matched nonsmoking individuals were used as the reference group. RESULTS: All sarcoidosis tissues showed strong staining for TRACP5a and CD68 in the non-caseating granulomatous lesions and localized specifically to MΦ, multinucleate giant cells, and epithelioid MΦ. Serum TRACP5a protein was elevated significantly in active sarcoidosis patients compared with the control group, and levels fluctuated with disease activity in one patient studied longitudinally. CONCLUSION: TRACP5a protein is expressed abundantly in the granulomatous tissues and may be elevated in a significant proportion of sarcoidosis patients. These findings further support our hypothesis that serum TRACP5a is derived from systemic inflammatory MΦ and thereby may be a biomarker of inflammation for sarcoidosis and also reflect its disease activity.
24701346 The role of gender in juvenile idiopathic arthritis-associated uveitis. 2014 Uveitis is a common complication of juvenile idiopathic arthritis (JIA) affecting up to 30% of patients with JIA. Although the typical bilateral chronic anterior uveitis associated with the persistent and extended oligoarticular and polyarticular, rheumatoid factor negative variants of JIA occurs predominantly in girls, boys may be more commonly affected in the HLA-B27 positive, enthesitis variant of JIA. While female gender has been associated with the development of the chronic anterior uveitis in children with JIA, the clinical course of JIA-associated uveitis may be worse in boys than in girls. The purpose of this paper is to review the available published literature to determine the role of gender in the clinical presentation and outcomes of patients with JIA-associated uveitis.
25780715 Research on Korean Pharmacopuncture in South Korea since 2007. 2014 Dec OBJECTIVES: The purpose of this study was to investigate the current trends in research on pharmacopuncture in Korea since 2007. METHODS: A literature review was performed by using the search engines 'Science and Technology Society Village', 'Korean Studies Information Service System', 'National Discovery for Science Leaders', and 'Oriental Medicine Advanced Searching Integrated System' in Korea from January 2007 to December 2013. Searched key words were 'pharmacopuncture', 'herbal acupuncture', 'aqua-acupuncture', and 'bee venom'. Finally, we selected 457 papers, including Korean experimental studies and clinical studies. Selected papers were classified according to year of publication, type of pharmacopuncture, disease & topic, research type and the publishing journal. RESULTS: One hundred fifty pharmacopunctures were studied in 457 papers. Single compound pharmacopuncture was the most studied pharmacopuncture in experimental studies while animal-based pharmacopuncture was the most studied pharmacopuncture in clinical studies. Bee venom placed first among the various pharmacopunctures, followed by placenta, sweet bee venom, mountain-ginseng, and anti-inflammatory pharmacopunctures. Experimental research on pharmacopuncture has fallen since 2007 when 55 papers were published. However, clinical research has been increasing steadily. In clinical studies, case reports were numerous than randomized clinical trials (RCTs). Musculoskeletal diseases were the most frequently-treated diseases in studies on pharmacopuncture; among the musculoskeletal diseases, rheumatoid arthritis was the most frequently-treated disease in experimental studies and low back pain was the most frequently-treated condition in clinical studies. Since 2007, 45 different journals have published studies on pharmacopuncture, with the Journal of the Korean Acupuncture and Moxibustion Medicine Society having the largest number of papers on pharmacopuncture and the Journal of Pharmacopuncture the second largest number. CONCLUSION: The trends in research on pharmacopuncture published in studies from 2007 to 2013 were similar to those in studies published before 2006. Many studies on pharmacopuncture focused on bee venom and musculoskeletal diseases. Additional studies on diverse types of and indications for pharmacopuncture are needed.
25594234 Frequency and causes of C-reactive protein and erythrocyte sedimentation rate disagreement 2015 Jan AIM: C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are often ordered together in patients with suspected infection or inflammation. However, the test results can disagree in as many as 33% of patients. Our aim was to further examine CRP/ESR disagreements and their stability on repeat testing. METHODS: We analyzed simultaneously ordered CRP and ESR results in 70 adult patients who had been tested on three separate occasions a median of 4 weeks apart. RESULTS: Initial CRP/ESR disagreements occurred in 14 of the 70 patients (20%; 95% CI, 12-31). Only four of these 14 patients had stable CRP/ESR disagreements throughout the study (two with lupus nephritis and one with osteomyelitis had persistent high ESR/normal CRP disagreements and one with rheumatoid arthritis had a persistent high CRP/normal ESR disagreement). The other 10 patients with initial CRP/ESR disagreements later exhibited CRP/ESR agreements. Of the 56 patients with initial CRP/ESR agreements, only 10 developed a CRP/ESR disagreement (or disagreements) on subsequent testing. CONCLUSION: CRP/ESR disagreements are common in clinical practice. Three mechanisms were identified to explain CRP/ESR disagreements: (i) slight fluctuations in the CRP and ESR around the upper limits of normal for these tests; (ii) development of an intercurrent illness; and (iii) different time courses of CRP and ESR elevations, in which the CRP rose and fell faster than the ESR.
25419153 A cosmeceutical formulation based on boswellic acids for the treatment of erythematous ecz 2014 BACKGROUND: Boswellic acids (BAs) show anti-inflammatory properties in a variety of inflammatory diseases, including rheumatoid arthritis, osteoarthritis, and asthma. A topical administration route is currently used to deliver active compounds in psoriatic and eczematous patients. In this double-blind study we compare a novel BA formulation (containing Bosexil(®), INCI [International Nomenclature of Cosmetic Ingredients]: lecithin, Boswellia serrata resin extract) with a placebo formulation. A third arm of the trial received a formulation of Vaccinium myrtillus seed oil, previously demonstrated as an effective local treatment for psoriatic lesions. METHODS: Patients with psoriasis or erythematous eczema were randomly assigned, in a 1:1:1 ratio, to Bosexil(®), V. myrtillus seed oil, or placebo. In order to evaluate the effects of treatment, the changes of scales and erythema from diagnosis to the end of treatment were scored in psoriatic patients, while changes in itch and erythema were analyzed for erythematous eczema patients. Psoriasis Area Severity Index and Eczema Area and Severity Index scores were also calculated. RESULTS: In patients with psoriasis, scales and erythema improved both with Bosexil(®) and the V. myrtillus seed oil treatment in comparison with placebo. In particular, the treatment with Bosexil(®) formulation improved scales (70% of cases) and erythema (50% of cases) without any case of worsening. In patients with eczema, the administration of placebo did not result in any improvement in 90% of cases, and in the remaining 10% worsened both itch and erythema. Bosexil(®) formulation improved both itch (60% of cases) and erythema (60% of cases) without any case of worsening. V. myrtillus seed oil improved itch and erythema in 66.7% and 77.8% of patients, respectively. CONCLUSION: A topical formulation of Bosexil(®) may be promising for the treatment of psoriasis and erythematous eczema. Long-term studies are recommended to evaluate the adherence to this topical treatment and its clinical benefits in real life.
25389506 Pulmonary Mycobacterium kansasii Infection Mimicking Malignancy on the (18)F-FDG PET Scan 2014 A 66-year-old male presented with chest pain, malaise, generalized weakness, and weight loss. He had been receiving etanercept injection for rheumatoid arthritis. Chest X-ray revealed a right upper lobe mass. Chest computed tomography (CT) showed a right apical mass, highly suggestive of a Pancoast tumor. The thoracic fluorine-18 fluoro-deoxy-glucose ((18)F-FDG) positron emission tomography (PET) scan demonstrated significantly high metabolic pulmonary lesions with the standardized uptake value (SUV) of 12.5, consistent with lung cancer. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL). BAL cytology was negative for malignant cells. BAL acid fast bacilli (AFB) smears were positive, and Mycobacterium kansasii was eventually isolated. He received a 12-month course of rifampin, isoniazid, and ethambutol. Interval resolution of pulmonary lesions was noted on follow-up serial CT chest studies. There has been increasing incidence of nontuberculous mycobacterial infections reported in patients treated with the antitumor necrosis factor-alpha (anti-TNF-alpha) agents. Infectious foci have an increased glucose metabolism which potentially causes a high FDG uptake on the (18)F-FDG PET scan, leading to undue anxiety and cost to the patients. This is the first reported case of pulmonary M. kansasii infection with a positive thoracic (18)F-FDG PET study mimicking malignancy in a patient on etanercept.
25309946 The Dynamic Duo-Inflammatory M1 macrophages and Th17 cells in Rheumatic Diseases. 2013 Nov 1 The synovial tissue of Rheumatoid Arthritis (RA) patients is enriched with macrophages and T lymphocytes which are two central players in the pathogenesis of RA. Interaction between myeloid cells and T cells are essential for the initiation and progression of the inflammatory processes in the synovium. With the rapid evolution of our understanding of how these two cell types are involved in the regulation of immune responses, RA is emerging as an ideal disease model for investigating the cell-cell interactions and consequently introducing novel biologic agents that are designed to disrupt these processes. This review will discuss the bidirectional interaction between the IL-23(+) inflammatory macrophages and IL-17(+) GM-CSF(+) CD4 T cells in rheumatic diseases as well as potential antirheumatic strategies via apoptosis induction in this context.
25275765 Impact of the 2012 London Olympic and Paralympic Games on physical activity of rheumatolog 2014 Oct BACKGROUND: Lack of physical activity in the general population is one of the biggest health challenges we face. For rheumatology patients, and other patients with chronic disease, exercise is an essential part of disease management. However, very few patients exercise effectively.One of the aspirations of the London 2012 Olympic/Paralympic Games was to catalyze people into long-term physical activity. METHODS: We surveyed our rheumatology patients at 3 high-profile times in the year after the Olympics. RESULTS: Two hundred fifty-three patients were enrolled within the study; the largest diagnosis subgroup being rheumatoid arthritis (36%). Ninety-five percent of our patients regard exercise as beneficial; 36% still think it does harm. Most common barriers to exercise were pain (53%), tiredness (44%), and lack of time (36%). Forty-five percent exercise daily, mostly just walking. Twnety-seven patients (16%) were motivated by the 2012 Olympic and Paralympic Games toward physical activity. They were mostly motivated by athletics' individual stories (67%), taking part in a big sports festival (11%) and demonstration of top sporting levels (4%). Eighteen patients in total (7%) increased their amount of exercise in response to the London 2012 Olympic and Paralympic Games. There was no difference between patient diagnostic groups. CONCLUSIONS: Only a small minority of patients increased their amount of exercise in response to the 2012 Olympic and Paralympic Games. The message about the importance of physical exercise to health needs to be clear, unambiguous, and consistent, because a significant number of patients still think that physical activity does harm. Big sporting events such as the London 2012 Olympic and Paralympic Games can be used as an opportunity to remind patients that physical activity does good and is not harmful. Athletes' individual stories could be used in future as part of a strategy to encourage exercise for all patients.
25241838 Intractable hematuria secondary to systemic amyloidosis with bladder involvement. 2014 Sep OBJECTIVE: To present the therapeutic management of intractable hematuria secondary to systemic amyloidosis with bladder involvement. METHODS: We describe the clinical case, the medical management, the endo-urological technique used, and the results supported by relevant published literature. RESULTS: A 50-year-old woman with a 20-year history of rheumatoid arthritis in chronic treatment with corticosteroids and non-steroidal anti-inflammatory drugs in addition to chronic renal insufficiency not requiring hemodialysis. Twenty-four hours after resection of a hepatic hydatid cyst she presented intractable hematuria. The ultrasound and CT scan showed the formation of a large blood clot in the bladder not affecting the upper urinary tract. An intra-operative cystoscopy revealed a distended bladder showing signs of inflammation with diffuse, widespread bleeding. Hemostasis was achieved and a biopsy of the mucosa was taken, associated to bladder irrigation with potassium alum as a hemostatic. Given the persistence of the hematuria, further revision in the operating room as well as blood transfusion were carried out and, due to the hemodynamic instability that could not be controlled, finally selective embolization was performed. Intravesical instillation of dimethyl sulphoxide every 72 hours was used to control any remaining hematuria. The biopsy showed bladder amyloidosis. The addition of intravenous steroids and orally administered colchicine successfully controlled the patient's clinical status. CONCLUSIONS: Secondary amyloidosis of the bladder is a condition associated with hematuria that is difficult to manage. Hematuria control is often difficult, requiring aggressive treatment in addition to more conservative approaches.
25186605 Peptides and peptidomimetics as immunomodulators. 2014 Peptides and peptidomimetics can function as immunomodulating agents by either blocking the immune response or stimulating the immune response to generate tolerance. Knowledge of B- or T-cell epitopes along with conformational constraints is important in the design of peptide-based immunomodulating agents. Work on the conformational aspects of peptides, synthesis and modified amino acid side chains have contributed to the development of a new generation of therapeutic agents for autoimmune diseases and cancer. The design of peptides/peptidomimetics for immunomodulation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus and HIV infection is reviewed. In cancer therapy, peptide epitopes are used in such a way that the body is trained to recognize and fight the cancer cells locally as well as systemically.