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ID PMID Title PublicationDate abstract
17032600 [Life-threatening liver failure and severe dyscrasias in blood and lymph nodes caused by s 2006 Sep 25 We report a case of sulphasalazine-related drug-induced hypersensitivity syndrome (the "three-week sulphasalazine syndrome") in which periferal T-cell lymphoma was a provisory diagnosis. A 40-year-old woman with seropositive rheumatoid arthritis was admitted to a local hospital 26 days after initiation of sulphasalazine treatment. She had fever, lymphadenopathy, dermatitis and facial oedema and showed biochemical signs of progressive hepatitis. Peripheral blood counts showed elevated leucocyte count with 15% atypical plasmacytes. Lymph node biopsy showed altered follicular architecture, a diffuse CD 4 positive predominance and histiocytes with erythrophagocytosis. Investigation by gene rearrangement for clonality of B- and T-lymphocytes ruled out the suspicion of lymphoma. Haematological and near-fatal hepatological changes resolved following discontinuation of sulphasalazine and a three-week course of glucocorticoid therapy. Early awareness of this syndrome via measuring liver function tests on, e.g., days 14-35 in patients started on sulphasalazine is recommended.
17127204 Infection and musculoskeletal conditions: Imaging of musculoskeletal infections. 2006 Dec Imaging procedures are routinely used to evaluate patients suspected of having musculoskeletal infection. Radiographs should be performed whenever musculoskeletal infection is suspected. Even when not diagnostic, radiographs are useful. They provide an anatomic overview of the region of interest, including pre-existing conditions that could influence the selection and interpretation of subsequent procedures. Magnetic resonance imaging (MRI) is sensitive, provides superb anatomic detail, does not use ionizing radiation, and is rapidly completed. This technique is especially valuable for septic arthritis, spinal osteomyelitis, and diabetic foot infections. Among the radionuclide procedures, three-phase bone imaging is readily available, and very accurate in unviolated bone. Labeled leukocyte imaging should be used in cases of 'complicating osteomyelitis' such as prosthetic joint infections. This test is also useful in unsuspected diabetic pedal osteomyelitis and the neuropathic joint. Gallium imaging is a useful adjunct to MIR in spinal infection. 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) will likely play an important role, especially in the evaluation of spinal infection.
18400834 Role of hypoxia-inducible factor-1alpha in hypoxia-induced expressions of IL-8, MMP-1 and 2008 Jun OBJECTIVES: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a master regulator in the cellular response to hypoxic conditions, and rheumatoid synovial tissue is known to exist under hypoxic conditions. Therefore, this study was conducted to determine the contribution of HIF-1alpha to hypoxia-induced MMP and cytokine production in fibroblast-like synoviocytes (FLS). METHODS: RA FLS were transfected with either a plasmid that expresses HIF-1alpha or an empty vector as a control, and then cultured under normoxia (21% O(2)). Also, FLS were transfected with either HIF-1alpha small interfering RNA (siRNA) or control siRNA, and cultured under hypoxic conditions (1% O(2)). Following transfection, the amounts of MMP and cytokine mRNAs and HIF-1alpha protein were examined using real-time RT-PCR and western blotting, respectively. RESULTS: The expression of HIF-1alpha, MMP-1, MMP-3, IL-6 and IL-8 was markedly enhanced in FLS that were cultured under hypoxia. We confirmed that transient transfection of HIF-1alpha overexpressing vector or siRNA had occurred using western blotting, and in vitro studies conducted using FLS transfected with HIF-1alpha overexpression vector showed that they had significantly increased MMP-1, MMP-3 and IL-8 expression levels. Further, hypoxia-induced MMP-3 expression was significantly attenuated by knock-down of HIF-1alpha, whereas hypoxia-induced IL-8 or MMP-1 expression was not significantly repressed by HIF-1alpha siRNA. CONCLUSIONS: Hypoxia-induced MMP-3 expression is exclusively regulated by HIF-1alpha, and hypoxia-induced MMP-1 or IL-8 expression appears to have salvage pathways other than the HIF-1alpha pathway. Together, these data provide new insight regarding the mechanism by which hypoxia participates in joint inflammation and destruction in RA.
18000689 Mediastinal migration of distal occipito-thoracic instrumentation. 2008 Sep We present the occurrence and management of mediastinal migration of the distal aspect of a posterior occipito-thoracic screw-rod construct. No similar occurrence was found in the literature. This event occurred following an emergency tracheotomy (requiring neck hyperextension) in a patient with severe rheumatoid arthritis, who had previously undergone decompression and an Occiput-T2 instrumented fusion for cranio-cervical and sub-axial cervical spine instability. Imaging showed fracture-subluxation of T1/2 and T2/3 with the bilateral C7, T1 and T2 screws in the mediastinum causing tracheal and esophageal compression. Removal of the instrumentation, decompression (T2 corpectomy) and construct revision down to T10 was safely performed from a posterior approach. Severe osteoporosis, some pre-existing screw loosening and hyperextension of the neck were the predisposing factors of this near catastrophic event. By staying directly posterior to the rod and following the fibrous tract already created, the instrumentation was safely removed from the mediastinum.
18709696 SLC22A4 polymorphism and rheumatoid arthritis susceptibility: a replication study in a Jap 2008 Sep OBJECTIVE: The SLC22A4 polymorphisms slc2F1 (rs2073838) and slc2F2 (rs3792876) are reported to be associated with rheumatoid arthritis (RA) in Japanese, but the associations have not been replicated. We assessed the RA susceptibility of slc2F1/F2 polymorphisms. METHODS: We conducted a metaanalysis for slc2F1/F2 polymorphisms to RA susceptibility, which included the replication study of an independent Japanese population consisting of 924 cases and 940 controls. A total of 9 studies (4 Japanese studies, 5 Caucasian studies) consisting of 8076 cases and 6837 controls were included in the metaanalysis. RESULTS: The replication study demonstrated significant associations in a Japanese population (OR 1.20, 95% CI 1.04-1.37, p = 0.0099, in the allelic mode; OR 1.29, 95% CI 1.08-1.55, p = 0.006, in the dominant mode; p = 0.011 in the trend mode). Significant ethnic diversities of allele frequencies of slc2F1/F2 polymorphisms were found (p = 8.6*10(-8)) between Caucasian and Japanese populations (0.07-0.08 and 0.30-0.32, respectively). The metaanalysis demonstrated significant associations for all studies (fixed-effect OR 1.11, 95% CI 1.05-1.18, p = 0.00084; random-effect OR 1.10, 95% CI 1.02-1.19, p = 0.017 in the allelic mode). Although subgroup analysis did not detect a significant association within Caucasian studies, significant associations were found within Japanese studies (fixed-effect and random-effect OR 1.16, 95% CI 1.07-1.25, p = 0.00012 in the allelic mode). CONCLUSION: The associations in Caucasian studies were not significant. Since the significantly low frequency of the risk allele made statistical power lower in Caucasians than in Japanese, whether significant relative risks existed in Caucasian populations was inconclusive. The significant relative risks in Japanese populations were confirmed.
17143972 Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis suscep 2007 Jan OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) promoter -308 A/G polymorphism has been reported to be associated with rheumatoid arthritis (RA) with inconsistent results. We investigated whether TNF-alpha -308 A/G polymorphism confers susceptibility to RA. METHODS: We conducted a random effect metaanalysis on the association of genotypes A/A (recessive effect), A/A + A/G (dominant effect), A allele, and A/A vs G/G genotypes of the TNF-alpha -308 polymorphisms with RA overall and within different ethnic populations. RESULTS: Fourteen studies, 10 of Europeans, 3 of Latin Americans, and one Asian, were included in this metaanalysis. An association between RA and the TNF-alpha -308 A allele was not found in the overall population (OR 1.005, 95% CI 0.715-1.412, p = 0.976). However, stratification by ethnicity indicated that the TNF-alpha A allele was significantly associated with RA in Latin Americans (OR 2.004, 95% CI 1.158-3.467, p = 0.013). Conversely, there was no association detected for the TNF-alpha A allele with RA patients from the European samples (OR 0.911, 95% CI 0.684-1.212, p = 0.520). The OR for the A/A + A/G genotype, the A/A genotypes, and the A/A vs G/G genotypes in samples overall and in each ethnic group showed a similar trend to those for the TNF-alpha A allele. CONCLUSION: This metaanalysis demonstrates that the TNF-alpha -308 A/G polymorphism may represent a significant risk factor for RA in Latin Americans, but not in Europeans.
18721278 Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid arthritis 2008 Aug Human allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein primarily identified in human and rat allografts, and data from several studies suggest an important role for AIF-1 in inflammatory processes. The aim of this study was to examine the association between AIF1 rs2269475:C>T polymorphism and rheumatoid arthritis (RA). AIF1 genotype was determined by means of the polymerase chain reaction-restriction fragment length polymorphism method in 276 White patients with RA and 236 healthy subjects. The frequency of the AIF1 rs2269475 TT genotype was significantly higher in the patients with RA than in the controls (OR=5.59, 95% CI: 1.22-25.55). The frequency of T allele carriers in the patient group with RA was 31.9% vs 19.1% among controls (P=0.0003). Moreover, the frequency of individuals positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies was significantly elevated in the T allele carriers (OR=8.82, 95% CI: 2.06-37.7). It is noteworthy that no significant linkage disequilibria between the AIF1 C/T and DRB1 alleles associated with RA development and anti-CCP antibody production [including the most frequent, i.e. *04 (32.7%) and *01 (23.5%)] (P>0.1) were found. Our results show that the AIF1 rs2269475 T allele is associated with increased risk of RA development. Moreover, the frequency of individuals positive for anti-CCP antibodies is significantly increased among T allele carriers.
16248997 The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern 2006 Apr Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.
17971359 Association of the nitric oxide synthase (eNOS) gene polymorphism with increased risk for 2007 Nitric oxide (NO), a short-lived gaseous free radical, synthesized from L-arginine by NO synthases (NOS), is a potent mediator of biologic responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Most biological necessary NO is produced by the family of three NOS. To date, several functionally relevant genetic polymorphisms in the eNOS gene have been associated with various vascular, infectious and autoimmune diseases. To our knowledge, no study has explored these polymorphisms for both SLE and RA in the same population. The objective of this study was to investigate the influence of the eNOS gene intron 4 a/b VNTR polymorphism (a 27-base-pair tandem repeat-based polymorphism) on susceptibility to SLE and RA in patients living in the island of Crete, a genetically homogeneous population. A group of 145 healthy subjects and 190 SLE patients were included in this study. Similarly, a second group of 235 healthy controls and 202 RA patients were analysed. In both cases, patients and controls were sex- and age-matched. Herein we report that the presence of a/b genotype of the eNOS gene may act as a risk factor not for the presence of SLE but for the development of glomerulonephritis (OR 2.71, 95% CI: 1.4-5.2), while it may be a susceptibility gene for RA (OR: 2.005, 95% CI: 1.31-3.07). Thus, in our population, the a/b genotype of the eNOS gene represents a severity rather than a susceptibility genotype for SLE.
18378918 A prospective randomised controlled trial of autologous retransfusion in total knee replac 2008 Apr We undertook a prospective randomised controlled trial to investigate the efficacy of autologous retransfusion drains in reducing the need for allogenic blood requirement after unilateral total knee replacement. We also monitored the incidence of post-operative complications. There were 86 patients in the control group, receiving standard care with a vacuum drain, and 92 who received an autologous drain and were retransfused postoperatively. Following serial haemoglobin measurements at 24, 48 and 72 hours, we found no difference in the need for allogenic blood between the two groups (control group 15.1%, retransfusion group 13% (p = 0.439)). The incidence of post-operative complications, such as wound infection, deep-vein thrombosis and chest infection, was also comparable between the groups. There were no adverse reactions associated with the retransfusion of autologous blood. Based on this study, the cost-effectiveness and continued use of autologous drains in total knee replacement should be questioned.
17016220 Outcomes of shoulder arthroplasty in Olmsted County, Minnesota: a population-based study. 2007 Feb Most studies on shoulder arthroplasty include a diverse group of patients presenting to a tertiary care center. Little information is available regarding outcomes in a community setting. We reviewed 98 residents (110 shoulders) of Olmsted County, Minnesota who had shoulder arthroplasties from 1976 to 2000. There were 65 total shoulder arthroplasties and 45 humeral head replacements. The most common indications were osteoarthritis for total shoulder arthroplasties (48/65) and acute fracture for hemiarthroplasties (27/45). The Neer ratings were excellent or satisfactory in 92% of total shoulder arthroplasties and 56% of hemiarthroplasties. The 10-year survival rate was 96%. The mean postoperative active forward elevation was greater in patients who had a total shoulder arthroplasty (132 degrees) compared with a hemiarthroplasty (113 degrees), as was external rotation (total shoulder arthroplasties = 58 degrees, humeral head replacements = 38 degrees). The outcomes for total shoulder arthroplasty and hemiarthroplasty compared favorably with outcomes reported in the literature. There was a high rate of satisfactory or excellent results after total shoulder arthroplasty for osteoarthritis. Hemiarthroplasty offered less satisfactory results, most likely related to the use of this procedure for trauma. This information will assist the community surgeon in counseling patients and weighing the risks and benefits of a shoulder arthroplasty.
18240240 Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvan 2008 Feb OBJECTIVE: Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant-induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM-1 and EM-2 has never been investigated in OA and RA. METHODS: We established a highly sensitive radioimmunoassay to detect EM-1 and EM-2. In patients with RA and patients with OA, immunohistochemistry for EM-1 and EM-2 was performed, and double-staining was used to identify EM-positive cells. The effects of EM-1 and EM-2 on the secretion of interleukin-6 (IL-6) and IL-8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM-1 were tested in a rat model of adjuvant-induced polyarthritis. RESULTS: EM-positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM-positive cells was higher in patients with OA than in those with RA. EM-1 inhibited synovial secretion of IL-6 in patients with RA and secretion of IL-8 in patients with RA and those with OA (maximum 10(-10)M). EM-2 inhibited IL-8 secretion only from RA tissue (maximum 10(-10)M). In rats with adjuvant-induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM-1 than was observed in controls. Rats with adjuvant-induced polyarthritis benefited from EM-1 treatment. CONCLUSION: EM-1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant-induced polyarthritis. Local enhancement of EM-1 might be an interesting therapeutic option in different forms of arthritis.
18477997 Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. 2008 Jul Despite the high prevalence and morbidity of osteoarthritis (OA), an effective treatment for this disease is currently lacking. Restoration of the diseased articular cartilage in patients with OA is, therefore, a challenge of considerable appeal to researchers and clinicians. Techniques that cause multipotent adult mesenchymal stem cells (MSCs) to differentiate into cells of the chondrogenic lineage have led to a variety of experimental strategies to investigate whether MSCs instead of chondrocytes can be used for the regeneration and maintenance of articular cartilage. MSC-based strategies should provide practical advantages for the patient with OA. These strategies include use of MSCs as progenitor cells to engineer cartilage implants that can be used to repair chondral and osteochondral lesions, or as trophic producers of bioactive factors to initiate endogenous regenerative activities in the OA joint. Targeted gene therapy might further enhance these activities of MSCs. Delivery of MSCs might be attained by direct intra-articular injection or by graft of engineered constructs derived from cell-seeded scaffolds; this latter approach could provide a three-dimensional construct with mechanical properties that are congruous with the weight-bearing function of the joint. Promising experimental and clinical data are beginning to emerge in support of the use of MSCs for regenerative applications.
18781962 Genetic susceptibility to autoimmune disorders: clues from gene association and gene expre 2008 Sep Susceptibility to autoimmune disorders results from the interaction of multiple genetic factors that regulate the threshold of autoreactivity. Genome-wide microsatellite screens and large-scale single nucleotide polymorphism (SNP) association studies have identified chromosomal loci that are associated with specific disorders including systemic lupus erythematosus, rheumatoid arthritis, juvenile arthritis, multiple sclerosis, and diabetes. Numerous candidate gene association studies have in turn investigated the association of specific genes within these chromosomal regions, with susceptibility to autoimmune diseases (e.g. FcgammaReceptors, TYK2 and systemic lupus). More recently, large-scale differential gene expression studies performed on selected tissues from patients with autoimmune disorders, have led to the identification of gene signatures associated with the activation of specific pathways in these diseases (e.g. interferon signature in lupus). In the future, integrated analyses of gene (and protein) expression together with SNP data will allow us to sketch an intelligible picture of the genesis of autoimmunity in humans. This review sets out to illustrate how the most recent advances in the field of systemic lupus erythematosus, rheumatoid arthritis and juvenile arthritis have led to a better understanding of these disorders.
16982117 [Aspergillosis in systemic diseases treated with steroids and/or immunosuppressive drugs: 2006 Nov This is a multicentric retrospective study of aspergillosis in patients treated by corticosteroids and/or immunosuppressive drugs for systemic diseases and a review of the literature. Nine patients, 5 men and 4 women, mean age of 62.8 years old were included among which Horton's diseases (3 cases), systemic lupus erythematosus (2), polymyositis (1), microscopic polyangiitis (1), idiopathic thrombocytopenic purpura (1), rheumatoid polyarthritis (1). Aspergillosis occurred in average 28.4 month after the diagnosis of systemic disease, and 28 months after the beginning of its treatment: corticosteroids in all cases, at a dose of 50.8 mg/day (equivalent prednisone) in average, cyclophosphamide (2 cases), methotrexate (1), intravenous immunoglobulins (1), leflunomide (1). All cases were invasive or chronic pulmonary aspergillosis located in the lungs (6 cases), or in the brain (3). Revealing symptoms were mild and non specific. Lymphopenia was severe in most cases, in average 472 lymphocytes/mm3 and 283 CD4+/mm3. The diagnosis was confirmed 20.75 days after the first symptoms in invasive aspergillosis, and 18.5 months in the chronic pulmonary cases, by cultures in 7 cases (broncho-alveolar lavage: 4; cerebral biopsy: 3), and direct microscopy examination of broncho-alveolar lavage in 2 cases. Specific serology was positive in 4 cases. Patients were treated by voriconazole (4 cases), itraconazole (2), amphotericin B (1), association of caspofungin and voriconazole (1), successive voriconazole and itraconazole (1). Six patients recovered from aspergillosis with 10.8 months of following time, 3 patients died a few days after confirmation of the diagnosis. Fifty-four cases of the literature are analysed.
17299730 Stereoselective disposition of fenoprofen in plasma and synovial fluid of patients with rh 2007 May 5 The simultaneous disposition of fenoprofen enantiomers in synovial fluid and plasma was studied in 11 patients with arthritis and chronic knee effusions treated with a single oral dose of 600 mg rac-fenoprofen. A plasma sample and a synovial fluid sample were collected simultaneously from each patient up to 16 h after the administration of fenoprofen. A stereospecific assay for fenoprofen using LC-MS-MS was developed and applied successfully to the analysis of the enantiomers in plasma (LOQ = 10 ng of each enantiomer/ml) and synovial fluid (LOQ = 25 ng of each enantiomer/ml). The values of the area under the curve (AUC) for the S-(+)-fenoprofen eutomer were approximately 2.5 times higher in plasma than in synovial fluid (256 vs 104 microg h/ml), while the values for the R-(-)-fenoprofen distomer were about four times higher in plasma than in synovial fluid (42.5 vs 10.5 microg h/ml). These data demonstrate accumulation of the S-(+)-fenoprofen eutomer in plasma and in synovial fluid, with concentrations versus time AUC (+)/(-) ratios of 6.0 in plasma and 9.9 in synovial fluid, suggesting a greater accumulation of the eutomer at the active site represented by synovial fluid than in plasma. This result demonstrates the importance of enantioselective methods and of analysis of synovial fluid rather than plasma in studies of the pharmacokinetics-pharmacodynamics of fenoprofen.
17144481 [Diagnostic problems in pleural involvement in systemic diseases]. 2006 Jul Pleuropulmonary manifestations in connective tissue diseases are frequent and variable. Pleural involvement is due especially to autoimmune inflammation and vasculitis, causing increased capillary permeability. Many of pleural effusions are asymptomatic, but with advancement in chest scanning techniques and immunohistology, pleuropulmonary abnormalities are increasingly being recognized in the early stages of a variety of connective tissue disease. The purpose of this article is to provide comprehensive information about incidence, pathophysiology, clinical manifestation and treatment for pleural diseases associated with connective tissue diseases.
19205321 Metallosis in revision total elbow arthroplasty. Complications and staging method. 2008 Dec Although total elbow arthroplasty is a reliable treatment method for the arthritic joint, revision is necessary if loosening, instability, wear, fracture or infection occurs. We report 12 patients with 19 months (10-29) follow-up after revision arthroplasty for painful loosening in six cases, periprosthetic fracture in three, gross instability in one and skin perforation with possible infection in two. All cases presented with severe metallosis. Fractures were seen in four, triceps insufficiency in three and skin perforation in two. All patients were treated with exchange arthroplasty using the Coonrad-Morrey prosthesis. Three patients had in addition strut-allografting. The two patients with skin perforation and possible infection had a staged procedure. Mayo Elbow Performance Score improved from 24 to 87 with uneventful healing, fracture consolidation and allograft incorporation. At follow-up, triceps insufficiency persisted in all three cases. Transient neuropathy was present in five patients (4 ulnar, 1 radial). Metallosis in total elbow arthroplasty may be associated with severe tissue damage. A staging method is presented.
17327660 Dose evaluation of boron neutron capture synovectomy using the THOR epithermal neutron bea 2007 Mar 21 Rheumatoid arthritis is one of the most common epidemic diseases in the world. For some patients, the treatment with steroids or nonsteroidal anti-inflammatory drugs is not effective, thus necessitating physical removal of the inflamed synovium. Alternative approaches other than surgery will provide appropriate disease control and improve the patient's quality of life. In this research, we evaluated the feasibility of conducting boron neutron capture synovectomy (BNCS) with the Tsing Hua open-pool reactor (THOR) as a neutron source. Monte Carlo simulations were performed with arthritic joint models and uncertainties were within 5%. The collimator, reflector and boron concentration were optimized to reduce the treatment time and normal tissue doses. For the knee joint, polyethylene with 40%-enriched Li(2)CO(3) was used as the collimator material, and a rear reflector of 15 cm thick graphite and side reflector of 10 cm thick graphite were chosen. The optimized treatment time was 5.4 min for the parallel-opposed irradiation. For the finger joint, polymethyl methacrylate was used as the reflector material. The treatment time can be reduced to 3.1 min, while skin and bone doses can be effectively reduced by approximately 9% compared with treatment using the graphite reflector. We conclude that using THOR as a treatment modality for BNCS could be a feasible alternative in clinical practice.
18617548 A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid arthritis. 2008 Sep OBJECTIVE: Environmental factors are involved in RA pathogenesis and epidemiological studies have suggested that smoking is an environmental risk factor for RA. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the major toxic components in cigarettes. To clarify the biological effects of smoking in RA, we investigated the role of TCDD in RA pathogenesis. METHODS: Human synovial tissue was obtained from RA and OA patients and aryl hydrocarbon receptor (AhR) expression in these tissues was evaluated using immunohistochemistry and real-time PCR. Expression of various cytokines was measured by real-time PCR following stimulation of RA synoviocytes with different concentrations of TCDD. To study the role of AhR, we treated RA synoviocytes with alpha-naphthoflavone, a known AhR antagonist. To evaluate which signal transduction pathways were stimulated by the TCDD-AhR interaction, we used inhibitors of nuclear factor-kappaB (NF-kappaB) and extra-cellular stimulus-activated kinase (ERK). RESULTS: Higher AhR mRNA and protein levels were observed in RA synovial tissue than in OA tissue. TCDD up-regulated the expression of IL-1beta, IL-6 and IL-8 through binding to AhR, and this effect was transmitted via the NF-kappaB and ERK signalling cascades. AhR expression in synovial cells was up-regulated by TNF-alpha. CONCLUSION: TNF-alpha activates AhR expression in RA synovial tissue, and that cigarette smoking and exposure to TCDD enhances RA inflammatory processes. TCDD induces inflammatory cytokines via its association with AhR, resulting in stimulation of the NF-kappaB and ERK signalling cascades. Thus TCDD exposure, such as smoking exacerbates RA pathophysiology.