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ID PMID Title PublicationDate abstract
16244831 [Imaging techniques in rheumatology: conventional radiography in rheumatoid arthritis]. 2005 Oct Conventional radiography is still regarded the gold standard for imaging techniques in rheumatoid arthritis (RA). It is a very important tool for the diagnosis, the differential diagnosis, and the evaluation of the course and prognosis of the disease. Special advantages of conventional radiography are the worldwide availability and experience with the method over decades and the relatively low costs. Moreover, x-rays can be stored and re-evaluated over long periods of time. Joint damage caused by RA can be quantified by means of scoring methods. The amount of destruction correlates well with functional disability over time. The inhibition of damage progression seen on radiographs is the most important characteristic of a DMARD. Typical radiographic changes are part of the ACR classification criteria of RA. Technically, bone structure can be demonstrated with a high local resolution better than with all other imaging techniques, whereas only indirect conclusions can be drawn concerning soft tissue and cartilage lesions. This review includes recommendations given by the "Commission on Imaging Techniques" of the German Society of Rheumatology regarding technical and personal preconditions, costs, indication as well as practical performance of radiography in RA. In addition, radiographic changes that can be expected in RA including destruction and repair are discussed briefly.
16142743 Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiolo 2005 Sep OBJECTIVE: To evaluate the dehydroascorbate (DHA) transport mechanisms in human chondrocytes. METHODS: The transport of L-(14)C-DHA in human chondrocytes was analyzed under various conditions, including the use of RNA interference (RNAi), to determine the role of glucose transporter 1 (GLUT-1) and GLUT-3 in L-14C-DHA transport and to evaluate the effects of physiologically relevant oxygen tensions on L-14C-DHA transport. In order to estimate the contributions of reduced ascorbic acid (AA) and DHA to intracellular ascorbic acid (Asc), the quantities of AA and DHA were measured in synovial fluid samples from osteoarthritis (OA) patients and compared with the reported levels in rheumatoid arthritis (RA) patients. RESULTS: DHA transport in human chondrocytes was glucose-sensitive, temperature-dependent, cytochalasin B-inhibitable, modestly stereoselective for L-DHA, and up-regulated by low oxygen tension. Based on the RNAi results, GLUT-1 mediated, at least in part, the uptake of DHA, whereas GLUT-3 had a minimal effect on DHA transport. DHA constituted a mean 8% of the total Asc in the synovial fluid of OA joints, in contrast to 80% of the reported total Asc in RA joints. CONCLUSION: We provide the first evidence that chondrocytes transport DHA via the GLUTs and that this transport mechanism is modestly selective for L-DHA. In the setting of up-regulated DHA transport at low oxygen tensions, DHA would contribute 26% of the total intracellular Asc in OA chondrocytes and 94% of that in RA chondrocytes. These results demonstrate that DHA is a physiologically relevant source of Asc for chondrocytes, particularly in the setting of an inflammatory arthritis, such as RA.
16331752 Extravasation into synovial tissue induces CCL20 mRNA expression in polymorphonuclear neut 2005 Dec OBJECTIVE: Examination of expression of the chemokine macrophage inflammatory protein-3a (CCL20/Mip-3alpha) in blood polymorphonuclear neutrophils (PMN) and synovial fluid (SF) PMN of patients with rheumatoid arthritis (RA). METHODS: Paired samples of blood PMN and SF PMN were obtained from 11 patients with RA. In addition, SF was prepared from 9 patients with osteoarthritis (OA) and 10 patients with juvenile idiopathic arthritis (JIA). PMN were isolated via density centrifugation to a purity of 98%. Total RNA was isolated and the expression of CCL20 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. In some experiments blood PMN obtained from healthy donors were stimulated with individual SF of patients with RA. For quantitative considerations, CXCL8, CCL20, interleukin 1, and tumor necrosis factor-alpha (TNF-alpha) levels were determined in SF by ELISA. RESULTS: In SF of RA patients CCL20 and CXCL8 levels were elevated, up to 7.5 ng/ml and 23.6 ng/ml, respectively. No significant level of either chemokine was found in SF of patients with JIA and OA. CCL20 mRNA was undetectable in blood PMN of all patients with RA. In SF PMN, CCL20 mRNA was found in 6/11 RA patients. Expression of CCL20 mRNA in 5/6 SF PMN samples was observed in the absence of detectable TNF-alpha levels in SF. Cell culture experiments, however, confirmed the ability of TNF-alpha in SF to induce CCL20 mRNA expression in blood PMN. Notably, expression of CCL20 was also found in PMN after stimulation with SF lacking TNF-alpha. CONCLUSION: Recruitment of PMN to the synovial microenvironment induces expression of CCL20 mRNA independent of the concentrations of TNF-alpha accumulating in SF of patients with RA.
15680868 Post-coronary artery bypass graft liver failure: a possible association with leflunomide. 2005 Feb We report the case of a 75-year-old woman who died of liver failure following coronary artery bypass grafting. The possibility of an association with leflunomide is discussed.
15752429 A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is ind 2005 Mar 7 BACKGROUND: The recruitment of lymphocytes to secondary lymphoid organs relies on interactions of circulating cells with high endothelial venules (HEV). HEV are exclusive to these organs under physiological conditions, but they can develop in chronically-inflamed tissues. The interaction of L-selectin on lymphocytes with sulfated glycoprotein ligands on HEV results in lymphocyte rolling, which represents the initial step in lymphocyte homing. HEV expression of GlcNAc6ST-2 (also known as HEC-GlcNAc6ST, GST-3, LSST or CHST4), an HEV-restricted sulfotransferase, is essential for the elaboration of L-selectin functional ligands as well as a critical epitope recognized by MECA-79 mAb. RESULTS: We examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA) synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-alpha and lymphotoxin-alphabeta induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells. CONCLUSION: These observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA.
17065118 NeuFlex compared with Sutter prostheses: a blind, prospective, randomised comparison of Si 2006 Forty patients (156 metacarpophalangeal joints) with mutilating rheumatoid arthritis were randomly allocated in a blinded manner to have either NeuFlex or Sutter implants. Indications for operation were pain and severe deformity. Thirty-nine patients were followed up postoperatively for one year. An independent physiotherapist and occupational therapist examined each one. Grip strength, range of motion, and pain during activity and at rest were measured. The Canadian Occupational Performance Measure (COPM) assessed the patients' evaluation of their occupational performance. Both groups had overall good results, but it seems that though patients' mobility and grip strength improve considerably, pain seems to do so only relatively. Most patients seem to be satisfied with the operation and their functional gain. Five out of 78 Sutter and two out of 78 NeuFlex implants broke. We found no major differences between the two designs, but the patients in the NeuFlex group seemed to be more satisfied with their occupational performance (COPM performance) (p=0.05).
16831656 Long-term results with the Kudo type 3 total elbow arthroplasty. 2006 Jul From 1992 to 1993, 17 elbows were replaced with the unlinked Kudo type 3 total elbow arthroplasty in 16 patients with arthritic joint destruction. Of these elbows, 8 were available for clinical examination after a mean of 9.5 years. Of the 17 elbow implants, 5 were revised: 2 because of loosening of the ulnar component, 1 because of dislocation, 1 because of a periprosthetic fracture, and 1 because of a late deep infection. At 9.5 years' follow-up, 67.9% of the prostheses had survived, and the mean survival of the implant was 8.7 years (95% confidence interval, 7.5-10 years). In this study, we observed high rates of progressive valgus tilting of the ulnar component. This valgus tilting is of major concern because it provides more stress to a smaller area on the polyethylene. It may, therefore, cause an increased degree of polyethylene wear and, thereby, reduce the final implant survival rate.
17117592 Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronar 2006 Nov Vertex Pharmaceuticals Inc, in collaboration with Kissei Pharmaceutical Co Ltd, is developing VX-702, one of a series of second-generation, orally active p38 MAP kinase inhibitors, for the potential treatment of inflammation, rheumatoid arthritis and cardiovascular diseases. In June 2005, a phase II clinical trial of VX-702 was initiated in rheumatoid arthritis. In July 2006, Vertex was planning to file an IND in the second half of 2006.
16257177 Investigating the genetic basis of susceptibility to rheumatoid arthritis. 2005 The challenges in identifying genetic polymorphisms that influence the susceptibility to rheumatoid arthritis are the same as those faced in most complex diseases; genetic and phenotypic heterogeneity, an unknown number of loci presumed to have small genetic effects, non-genetic modifying effects that have yet to be fully characterised and a history of unconfirmed genetic associations. Despite the difficulties, the chronic nature of the disease, incomplete efficacy of existing therapies and resultant heavy healthcare burden for the developed world in managing patients with this condition, mean that an understanding of the genetic basis of disease susceptibility, severity and response to therapy is keenly sought. Many linkage and association studies have been carried out and in this article the results of linkage studies are summarised. Recently a number of convincing candidate genes have begun to emerge and an update has been provided for three of these: PTPN22, CTLA-4 and MIF.
15743467 Microcirculation abnormalities in patients with fibromyalgia - measured by capillary micro 2005 This unblinded preliminary case-control study was done to demonstrate functional and structural changes in the microcirculation of patients with primary fibromyalgia (FM). We studied 10 women (54.0 +/- 3.7 years of age) with FM diagnosed in accordance with the classification criteria of the American College of Rheumatology, and controls in three groups (n = 10 in each group) - age-matched women who were healthy or who had rheumatoid arthritis or systemic scleroderma (SSc). All 40 subjects were tested within a 5-week period by the same investigators, using two noninvasive methods, laser fluxmetry and capillary microscopy. The FM patients were compared with the healthy controls (negative controls) and with rheumatoid arthritis patients and SSc patients (positive controls). FM patients had fewer capillaries in the nail fold (P < 0.001) and significantly more capillary dilatations (P < 0.05) and irregular formations (P < 0.01) than the healthy controls. Interestingly, the peripheral blood flow in FM patients was much less (P < 0.001) than in healthy controls but did not differ from that of SSc patients (P = 0.73). The data suggest that functional disturbances of microcirculation are present in FM patients and that morphological abnormalities may also influence their microcirculation.
16107513 Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence an 2006 Mar Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.
16029422 Early disease onset and increased risk of other autoimmune diseases in familial generalize 2005 Aug Generalized vitiligo is an autoimmune disorder in which acquired white patches of skin and overlying hair result from autoimmune loss of melanocytes from involved areas. Although usually sporadic, family clustering of vitiligo may occur, in a non-Mendelian pattern typical of multifactorial, polygenic inheritance. Sporadic vitiligo is associated with autoimmune thyroid disease, pernicious anemia, Addison's disease, and lupus; these same disorders occur at increased frequency in patients' first-degree relatives. Here, we studied 133 'multiplex' generalized vitiligo families, with multiple affected family members. The age of onset of vitiligo is earlier in these 'multiplex' families than in patients with sporadic vitiligo. Affected members of the multiplex vitiligo families have elevated frequencies of autoimmune thyroid disease, rheumatoid arthritis, psoriasis, adult-onset insulin-dependent diabetes mellitus, pernicious anemia, and Addison's disease. Probands' unaffected siblings have elevated frequencies of most of these same autoimmune diseases, particularly if the proband had non-vitiligo autoimmune disease. Familial generalized vitiligo is thus characterized by earlier disease onset and a broader repertoire of associated autoimmune diseases than sporadic vitiligo. This mostly likely reflects a greater inherited genetic component of autoimmune susceptibility in these families. These findings have important implications for autoimmune disease surveillance in families in which multiple members are affected with vitiligo.
16652418 Safety of infliximab used in combination with leflunomide or azathioprine in daily clinica 2006 May OBJECTIVE: To investigate the safety of infliximab (INF) combination therapy with leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis (RA). METHOD: A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period. Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed. RESULTS: Data on 225 patients with RA were collected retrospectively. INF was used in combination with LEF in 171 patients and with AZA in 54. The duration of INF exposure was similar in both groups (mean 8.8 mo). AE were reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion (5.3%), and skin reactions (4%). At the time the questionnaires were sent out, 161 patients were continuing combination therapies. The main reasons for drug withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one temporary discontinuation for surgery. CONCLUSION: Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations.
16969427 Combined cannabinoid therapy via an oromucosal spray. 2006 Aug Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.
17236388 Awake intubation using fast-track laryngeal mask airway as an alternative to fiberoptic br 2006 Dec Patients with rheumatoid arthritis (RA) pose a unique challenge to the anesthetist. The manifestations of RA may include cervical spine instability, limited range of motion, and temperomandibular joint involvement limiting mouth opening. Therefore, securing the airway while maintaining the head and neck in a neutral position is of particular concern to the anesthetist. While this is most commonly accomplished using an awake fiberoptic technique, the following case is presented as a safe and efficient initial alternative to the primary use of fiberoptic bronchoscopy in the appropriate patient population.
15889759 Dose adjustment over time of etanercept and infliximab in patients with rheumatoid arthrit 2005 Apr Dose escalation of biologics in patients with rheumatoid arthritis may affect the cost of care. Longitudinal claims data from a large U.S. health plan were analyzed retrospectively. A total of 4,426 health plan members had a medication claim for either etanercept (N = 690; mean age, 48.4 yr; 72% female) or infliximab (N = 424; mean age, 54.3 yr; 73% female) during the selection period. The study revealed that the mean dosage in patients receiving infliximab for rheumatoid arthritis symptoms increased by 29% from first to last dose. The mean weekly dosage for etanercept remained stable. Etanercept was associated with a significantly lower hazard of dose increase relative to infliximab. The estimated annual costs of infliximab and its administration varied by 31%, whereas the estimated costs of etanercept remained stable over time. This increased dose of infliximab may translate into increased costs for a payer over time.
16205926 Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 e 2006 May The objective of this study has been the well established fact that proinflammatory cytokines and metalloproteinases play a crucial role in the pathogenesis of chronic arthritis as well as the development of pannus, with the eventual erosive changes. Among the proinflammatory cytokines, interleukin-18 (IL-18) has been shown to contribute to the pathogenesis of chronic synovitis by increasing the secretion of interleukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) and also stimulating angiogenesis. The aim of this study is to investigate the synovial IL-18, IL-1beta, TNF-alpha and matrix metalloproteinase-3 (MMP-3) levels in patients with Behçet's disease (BD), and compare them with the levels of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). 30 patients with BD, 20 with RA, and 20 with OA were included in the study. The synovial levels of IL-18, IL-1beta, TNF-alpha and MMP-3 were detected using the two-step sandwich ELISA method. The synovial IL-18, TNF-alpha and MMP-3 levels were significantly higher in RA patients than patients with BD (P=0.004, 0.019, 0.025, respectively) and with OA (P=0.004, 0.045, 0.032, respectively). There were no differences, with respect to the cytokine levels, when patients with BD were compared with those with OA. Patients with RA and BD had higher IL-1beta levels than patients with OA (P=0.017, 0.013, respectively). However, no such difference was found for IL-1beta between BD and RA patients. Among patients with RA, positive correlations were found between TNF-alpha and MMP-3 (r=0.683, P=0.001). Our results showed that MMP-3 and proinflammatory cytokines, except IL-1beta, were expressed in relatively small quantities in Behçet's synovitis. Detection of the lower levels of these cytokines and metalloproteinases might explain the non-erosive character of Behçet's arthritis. We suggest that IL-1beta may be involved in the pathogenesis of Behçet's synovitis.
16697964 Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoi 2006 Apr Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases.
17343252 Heat shock protein 70 membrane expression on fibroblast-like synovial cells derived from s 2006 Nov OBJECTIVE: To screen fibroblast-like synovial cells derived from synovial tissue of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) patients for the membrane expression of the heat shock protein Hsp70. METHODS: We performed flow cytometric (fluorescence-activated cell sorting, or FACS) analysis on fibroblast-like synovial cells of 15 RA patients and three JIA patients to investigate Hsp70 membrane expression. Skin fibroblasts derived from the operation wound (n = 4) and peripheral blood mononuclear cells (PBMC) of seven RA and three JIA patients were also tested. Peripheral blood lymphocytes (PBL) and skin fibroblasts of 10 healthy individuals were used as negative controls. RESULTS: A significantly higher percentage of Hsp70 membrane expression was found on fibroblast-like synovial cells derived from arthritis-affected joints in RA patients (mean 47.7%) when compared with autologous skin fibroblasts (mean 9.5%, p < 0.001) and control skin fibroblasts (mean 5.6%, p < 0.001) or autologous PBL (mean CD45/Hsp70-positive 10.4%, p < 0.001) and control PBL (mean CD45/Hsp70-positive 7.7%, p < 0.001). A high percentage of Hsp70 membrane expression was also observed on fibroblast-like synovial cells derived from three patients with JIA (mean 35.2%) when compared with autologous PBL (mean CD45/Hsp70-positive 10.4%). Synovial cells derived from non-affected joints in a patient with RA who underwent synovectomy for trauma showed low expression of Hsp70 (10.9%). CONCLUSION: Fibroblast-like synovial cells derived from patients with severe course of RA and JIA are strongly positive for membrane-expressed Hsp70.
17033852 Ultrasound detects rapid progression of erosive disease in early rheumatoid arthritis: a p 2007 Feb OBJECTIVE: To evaluate and compare sequential ultrasound exams (US) with power-Doppler (PD) to radiography for the detection of synovitis and erosions in patients with early RA. METHODS: Radiographs and US with PD of the hands and feet were performed at baseline and 6+/- 2 months afterwards in 21 early RA patients. Their mean (range) age was 42.6 (21-81) years and the female/male ratio was 4:3; mean disease duration was 9 (1-28) months. Joints assessed were bilateral 2nd and 5th MCPs, 5th MTPs and the most swollen PIP in each hand, for a total of eight joints per patient. Radiographs (PA, lateral and pronated oblique) were read for erosions using the method of Sharp/van der Heijde. On US, erosions were defined as cortical defects greater than 2 mm in diameter with an irregular floor. Synovitis was rated as +1 (increase in joint fluid without synovial hyperemia), +2 (mild blood flow), +3 (moderate blood flow), and +4 (severe blood flow). Two blinded trained assessors read all images. RESULTS: US detected 15 erosions in 10 patients at baseline and 31 erosions in 12 patients on follow-up; radiographs could detect only one erosion at baseline and five erosions in three patients on follow-up. PD detected synovitis in all patients at baseline and on follow-up. Of the joints found to have synovitis, 64% were identified as such at baseline and 38% on follow-up. CONCLUSIONS: Sequential US can determine disease progression in patients with early RA. Such data may allow the clinician to treat RA patients earlier in the hope of preventing joint damage.