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ID PMID Title PublicationDate abstract
18568424 Kinase inhibitors for the treatment of inflammatory and autoimmune disorders. 2009 Mar Drugs targeting inhibition of kinases for the treatment of inflammation and autoimmune disorders have become a major focus in the pharmaceutical and biotech industry. Multiple kinases from different pathways have been the targets of interest in this endeavor. This review describes some of the recent developments in the search for inhibitors of IKK2, Syk, Lck, and JAK3 kinases. It is anticipated that some of these compounds or newer inhibitors of these kinases will be approved for the treatment of rheumatoid arthritis, psoriasis, organ transplantation, and other autoimmune diseases.
18466566 Power of the 2-locus TDT for testing the interaction of two susceptibility genes. 2007 We recently proposed a new strategy: 2-locus TDT for detecting two susceptibility genes through their interaction in trio families. We apply our method to two candidate genes, A and C, on the Genetic Analysis Workshop 15 (GAW15) simulated rheumatoid arthritis data and study the power to identify an interactive effect of these genes.This study was performed with full knowledge of the answers.
19005999 Do non-steroidal anti-inflammatory drugs influence chronic inflammation? The effects of pi 2008 Nov OBJECTIVE: The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on acute inflammation have been thoroughly investigated. NSAIDs are, however, also prescribed for patients with chronic inflammation, such as rheumatoid arthritis (RA), and objective improvement suggestive of anti-inflammatory action from NSAIDs has not been convincingly shown in chronic RA. An antigen-induced arthritis (AIA) model was used to investigate the effects of piroxicam on chronic inflammation. METHODS: AIA was induced by injecting methylated bovine serum albumin (mBSA) into the knee joints of previously immunized rats that were treated orally with the NSAID piroxicam or with saline. This treatment was started either before AIA was induced or after it had reached a chronic phase. The findings were recorded by clinical and histological assessment of the joints. RESULTS: The piroxicam group developed significantly less acute and subsequent chronic knee joint inflammation but this was only evident if the drug was administered prior to the intra-articular mBSA injections. Piroxicam treatment that was initiated during the chronic inflammation did not have any clinical effect, whereas short-term corticosteroid treatment abolished the chronic inflammation. Moreover, histological analysis of the chronic inflammation revealed significantly more inflammatory changes in the piroxicam group compared with the control group. CONCLUSIONS: Piroxicam treatment had no beneficial effects on the chronic stable inflammation in this model and might even delay histological resolution. As the anti-inflammatory effect of piroxicam is restricted to acute inflammation, the use of NSAIDs during periods of chronic stable arthritis in humans, such as in RA, may need to be investigated.
17348600 Improving patient outcomes with prayer. 2007 Jan Matthew's et al.'s (2000) study supported the use of prayer in rheumatoid arthritis patients. The results of this study can be used to support the group's research utilization project to educate nurses about the impact religion and prayer can have on patient outcomes. A suggestion for future research is to include a more widespread age group, ranging from school age children up to the older adult, as study participants. Two feasability issues for educating nurses about the benefits of prayer on patient outcomes are the time and money.
16752740 [Natural gas-steam-thermal springs in combined therapy of osteomuscular system diseases]. 2006 Jan The article describes effects of unique thermal springs of Yangan-Tau mountain in patients with locomotor diseases. Effects of gas, steam and thermal factors of the water from the above springs were studied in patients with rheumatoid arthritis who took baths in the sanatorium Yangan-Tau. Changes in the cytokine profile of the patients were analysed.
16981296 Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic a 2006 Nov OBJECTIVE: To compare the prevalence of cardiovascular diseases and their risk factors between patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) and control subjects. METHODS: Data for patients continuously enrolled in an integrated outcomes database between January 1, 2001, and December 31, 2002, with International Classification of Diseases, 9th Revision codes of 714.x (RA), 696.0 (PsA), or 720.0 (AS) were evaluated in this cross-sectional comparative study. Control groups were established for each patient group (1:4 ratio) by matching on the basis of age, sex, geographic region, and length of time in plan. Age- and sex-adjusted prevalence of cardiovascular comorbidities and risk factors were calculated; the prevalence ratio of the comorbidities and risk factors for the patient groups compared with the control population were estimated. Use of selected cardiovascular medications was also compared between patient and control groups. RESULTS: The RA, PsA, and AS cohorts comprised 28,208, 3066, and 1843 patients, respectively. The prevalence ratio of ischemic heart disease (1.5, 1.3, 1.2), atherosclerosis (1.9, 1.4, 1.5), peripheral vascular disease (2.4, 1.6, 1.6), congestive heart failure (2.0, 1.5, 1.8), cerebrovascular disease (1.6, 1.3, 1.7), type II diabetes (1.4, 1.5, 1.2), hyperlipidemia (1.2, 1.2, 1.2), and hypertension (1.3, 1.3, 1.3) were higher in patients than controls. For RA, PsA, and AS, use of angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics, nitrates/vasodilators, anticoagulants, and antihyperlipidemia agents was significantly higher in patients than controls. CONCLUSION: Cardiovascular diseases and their risk factors were more common in patients with RA, PsA, and AS than in matched controls.
17485531 Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhib 2007 Jun Beta interferon (IFN-beta) is a cytokine with potent immunomodulatory properties and has been described as a promising therapeutic molecule for the treatment of rheumatoid arthritis (RA). IFN-beta was previously overexpressed intra-articularly using an adenoviral vector in rats with adjuvant arthritis (AA) as a model of RA. This effect was powerful, albeit transient due to the vector chosen. Therefore, in the context of pre-clinical development, a delivery vector optimized for intra-articular gene transfer, recombinant adeno-associated virus type 5 (rAAV5), was selected. To exert an optimal effect, protein production should parallel the course of the disease. For this reason, the gene for IFN-beta was placed under the control of an inflammation-responsive [nuclear factor (NF)-kappaB] promoter. After intra-articular injection of the rAAV5 constructs in rats with AA, local transcription of the transgene and production of the IFN-beta protein was found, leading to a pronounced and sustained effect on paw swelling when the expression was under the control of the NF-kappaB-responsive promoter. Additionally, a significant beneficial effect was observed on proteoglycan depletion and erosions. Thus, intra-articular overexpression of IFN-beta using a rAAV5 vector exhibits potential as an innovative therapy for the treatment of RA.
17265437 Five types of inflammatory arthritis following total knee arthroplasty. 2007 Jun 15 Joint effusion after total knee arthroplasty (TKA) is considered as a manifestation of certain inflammatory reactions within prosthetic joints. This study investigated causes of joint effusion following TKA and analyzed phenotypic characteristics of synovial fluid leukocytes for each cause. Forty-six TKAs for rheumatoid arthritis (RA) and 49 TKAs for osteoarthritis (OA) displaying joint effusion were investigated. Causes of joint effusion were clinically identified and frequencies of each cause were compared between RA and OA. Synovial fluid cell phenotypes were analyzed using a fluorescence-activated cell sorter. Clinical diagnoses for joint effusion were classified into five different groups: deep infection (DI); increased activity of RA (IRA); particle-induced synovitis (PS); metal sensitivity (MS); and nonspecific synovitis (NS). The most frequent cause of post-TKA effusion was IRA in RA, and NS in OA. Biomaterial-related arthritis such as PS and MS were more frequent with OA than with RA. Analysis of synovial fluid cell phenotypes revealed that the characteristic cells for each diagnosis were CD16(+)CD14(-) neutrophils in IRA and DI, CD14(+) macrophages in PS, and CD3(+)CD45RO(+) T cells in MS. Post-TKA joint effusion is clinically caused by five different types of arthritis. Phenotypic characteristics of synovial fluid leukocytes reflect joint pathology and contribute to diagnosis and exclusion of biomaterial-related arthritis.
16942002 Hand arthritis in systemic lupus erythematosus: an ultrasound pictorial essay. 2006 A small minority of systemic lupus erythematosus (SLE) patients may develop a deforming arthritis, typically with a non-erosive (Jaccoud's) pattern, although erosive features indistinguishable from rheumatoid arthritis may also occur. High-resolution ultrasonography (HRUS) allows detailed 'real time' imaging of joint and tendon morphostructural changes involving the hand in patients with several rheumatic diseases. The main aim of this pictorial essay is to provide the first descriptive HRUS and power Doppler (PD) findings of joint and tendon involvement of the hand and wrist in patients with SLE arthritis. Seventeen patients with SLE and hand involvement were examined. HRUS of the wrist, 2nd and 3rd MCP joints, 3rd PIP joint and 2nd, 3rd and 4th finger flexor tendons were studied in the dominant hand for each patient. Sixteen (94%) patients had joint effusion or synovial hypertrophy in the wrist. Twelve (71%) patients had joint effusion or synovial hypertrophy in 2nd or 3rd MCPJs. Eight (47%) patients had erosion at 2nd or 3rd MCPJs. In three cases erosions were not present radiologically. Eleven (65%) patients had evidence of tenosynovitis. In SLE, HRUS with PD detects a high prevalence of inflammatory pathology in the tendons and synovium of the hand and wrist, and a high prevalence of MCP joint erosions. HRUS offers a sensitive, real-time and readily repeatable assessment of soft-tissue, inflammatory and bony changes in SLE hands.
17108524 Information technology in clinical research in rheumatology domain. 2006 The development of a functional clinical database of rheumatic diseases represents an essential step in the process of acquiring the necessary epidemiological and other information on disorders under study. In 1999-2005 the Institute of Rheumatology in cooperation with the EuroMISE Center has developed the Clinical database/National Register of selected systemic inflammatory rheumatic diseases inclusive of a bank of sera and DNA. Aims of this phase of the pilot research were gathering clinical, laboratory, genetic, pharmaco-and socio-economic data in a representative sample of patients with systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease; rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis. In 2002 the preset number of over 2000 registered patients had been achieved with collaboration of 34 territorial and 20 institutional rheumatologists in the whole covering the majority of the Czech Republic. Based on experiences gathered, the systems for other related studies are being developed and implemented using modern information technologies.
16958499 Infections and inflammatory conditions of the cervical spine in children. 2006 Because infections and inflammatory disorders of the cervical spine are uncommon in children and adolescents, diagnosis and treatment are frequently delayed. Intractable pain, limitation of neck motion, and neurologic compromise may occur as the result of these pathologic processes. It is important to identify these symptoms for early diagnosis and treatment of conditions such as bacterial and tuberculous infections, intervertebral disk calcification, juvenile rheumatoid arthritis, and Grisel's syndrome.
16995415 [Regulation of osteoclast activity: a new approach in the therapy of bone diseases]. 2006 Bone remodelling is process of constant resorption and formation of a bone. Osteoclasts are the cells responsible for bone resorption. Deregulation of osteoclast differentiation, activity or function can cause severe diseases, such as osteoporosis, osteopetrosis or rheumatoid arthritis. Advances in molecular biology of osteoclasts and osteoimmunology open new approaches for the specific and efficient therapy.
21603466 Infliximab-associated Chiasmopathy. 2008 Fall Optic neuropathy has been reported in association with the use of tumor necrosis factor-alpha antagonists such as etanercept, infliximab, and adalimumab. This is a report of a patient who began experiencing decreased vision approximately 1 month after starting infliximab therapy for rheumatoid arthritis. Visual field testing showed bitemporal hemianopic scotomas, indicating involvement of the nerve fibers in the optic chiasm. The infliximab was discontinued, and the patient experienced substantial improvement in her visual acuity and visual field.
18608173 Gene expression profiles at different stages of collagen-induced arthritis. 2008 Nov The molecular basis to autoimmune arthritis is unclear. To identify candidate molecules that may be involved in the development and progression of collagen-induced arthritis (CIA), an animal model for human rheumatoid arthritis, we used microarray and real-time PCR assays to examine the gene expression profiles at the onset, peak and decline phase of CIA. Our results showed that, of the 514 immune-related genes assayed in microarrays, fifty-eight genes showed differential expression with thirty-one up-regulated and twenty-seven down-regulated in CIA joints, in comparison to normal joint tissue. By real-time PCR, expression of some chemokines/chemokine receptors, such as CCR1, CXCR4, CXCL13 and MCP1, showed significantly elevated in the inflamed joints. Quite a few genes were significantly up- or down-regulated at the peak time point, which indicates their roles in the progression of the disease. In addition, the expression levels of some genes remained significantly elevated at all stages of the disease. These gene expression profiles may help understand the pathogenesis of the disease.
18438855 Profound and paradoxical impact on arthritis and autoimmunity of the rat antigen-presentin 2008 May OBJECTIVE: The antigen-presenting lectin-like receptor complex (APLEC) was recently identified as a genetic determinant for arthritis susceptibility. We undertook this study to define mechanisms underlying the impact of APLEC on arthritis, to determine whether sex effects occur, and to determine whether APLEC influences different types of arthritis and phenotypes other than susceptibility. METHODS: Arthritis-susceptible DA rats were compared with sex-matched congenic rats in which APLEC alleles were substituted with alleles from arthritis-resistant PVG rats. Six different arthritogenic agents were injected at the base of the tail: Freund's incomplete adjuvant, pristane, squalene, killed mycobacteria, yeast beta-glucan, or rat type II collagen (CII). Arthritis was visually scored, body weight was measured, and anti-CII IgG and cytokine messenger RNA (mRNA) levels were determined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. RESULTS: In 5 models of rheumatoid arthritis (RA), congenic rats deviated profoundly from DA rats by having reduced arthritis susceptibility, delayed onset, decreased severity, and/or reduced body weight loss. Paradoxical opposite genetic effects were noted, including a more severe disease course in congenic males in pristane-induced arthritis and decreased clinical signs in collagen-induced arthritis despite increased autoantibody levels. Interestingly, the anti-CII IgG isotype profile was skewed in congenic rats, and markedly reduced lymph node mRNA levels for interleukin-17 suggested that the cytokine profile of autoreactive T helper cells was also skewed in a less pathogenic direction. CONCLUSION: Rat APLEC regulates autoimmunity and multiple phenotypes in several types of arthritis. However, delineating the genetic impact may require stratification for sex or mode of arthritis induction. This pathogenetic complexity should be considered when evaluating APLEC in inflammatory and autoimmune diseases, including RA.
18797063 Hodgkin's lymphoma in a patient of psoriasis treated with long-term, low-dose methotrexate 2008 Jul Methotrexate (MTX) is used in the treatment of a variety of diseases such as rheumatoid arthritis, dermatomyositis, juvenile rheumatoid arthritis and chronic plaque psoriasis. It has been well documented that there is a risk of development of lymphomas in these patients although none have been reported in patients of psoriasis treated with methotrexate. A 58-year-old male patient, a known case of psoriasis since 1994, had been receiving treatment with a low dose of MTX, 5 mg weekly for ten years intermittently (7-8 months/year). The cumulative dose of MTX taken was 1.5 gm. He developed high-grade fever with cervical lymphadenopathy that was nonresponsive to routine line of management. Lymph node biopsy revealed the presence of mixed cellularity type of Hodgkin's lymphoma. CT scan showed cervical, mediastinal and abdominal lymphadenopathy. The patient responded well to withdrawal of MTX and chemotherapy. This is the first case of lymphoma occurring in a patient of psoriasis treated with low-dose MTX.
18466556 Two-stage approach for identifying single-nucleotide polymorphisms associated with rheumat 2007 We used the simulated data set from Genetic Analysis Workshop 15 Problem 3 to assess a two-stage approach for identifying single-nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA). In the first stage, we used random forests (RF) to screen large amounts of genetic data using the variable importance measure, which takes into account SNP interaction effects as well as main effects without requiring model specification. We used the simulated 9187 SNPs mimicking a 10 K SNP chip, along with covariates DR (the simulated DRB1 gentoype), smoking, and sex as input to the RF analyses with a training set consisting of 750 unrelated RA cases and 750 controls. We used an iterative RF screening procedure to identify a smaller set of variables for further analysis. In the second stage, we used the software program CaMML for producing Bayesian networks, and developed complex etiologic models for RA risk using the variables identified by our RF screening procedure. We evaluated the performance of this method using independent test data sets for up to 100 replicates.
18431089 Osteoporosis risk factor assessment increases the appropriate use of dual energy X-ray abs 2008 Feb BACKGROUND: Male patients are frequently not tested for osteoporosis even in the presence of recognized risk factors for that disease. OBJECTIVES: To evaluate if the assessment of risk factors for osteoporosis increases the utility of dual energy X-ray absorptiometry (DXA) in men over the age of 50 attending a rheumatology clinic. METHODS: Men over 50 attending a rheumatology clinic completed a checklist of 10 risk factors for osteoporosis before seeing the physician. The physician reviewed the checklist and made a management decision. The checklists and medical records were reviewed for medical history and DXA results. Comparisons were made with DXA requests before the use of the checklist. RESULTS: Medical records of 183 men were reviewed, including 111 African Americans (AA) and 67 whites. Twenty-three percent of patients had rheumatoid arthritis (14% of AA, 37% of whites) and 27% of patients were on glucococorticoids. Before the use of the checklist, 14% of men had a DXA (6% of AA and 29% of whites) compared with 29% of patients (21% for AA and 42% for whites) after the checklist was instituted in the clinic. Sixty-three percent of AA with rheumatoid arthritis had DXA compared with 65% of whites. Thirteen patients had osteoporosis whereas 16 had osteopenia. CONCLUSIONS: The use of a check list of risk factors for osteoporosis may increase the appropriate use of DXA in male patients over the age of 50 at risk for osteoporosis.
17934840 Treatment of Crohn's disease with leflunomide as second-line immunosuppression : a phase 1 2008 Apr The aim of this study was to assess the potential of leflunomide, an immunosuppressant in rheumatoid arthritis, as a second-line immunosuppression treatment of patients with Crohn's disease refractory or intolerant to azathioprine. The study cohort consisted of 24 patients. The primary end point was steroid-free remission, and secondary end points were changes in the Crohn's disease activity index (CDAI) and steroid intake, responsiveness of arthralgias and adverse events. Results were expressed in medians (quartiles). The remission rate increased from 21 to 42% by week 16 (P < 0.05). In the intention-to-treat analysis, the CDAI decreased from 219 to 87 (P = 0.018) and the steroid intake from 25 to 3 mg/day (P = 0.033). In the per-protocol analysis, the CDAI decreased from 182 to 87 (P = 0.0183) and the steroid intake from 45 to 4 mg/day (P = 0.0778). Patients with arthralgias improved significantly. However, adverse side effects were frequent. Leflunomide may improve disease activity, especially in terms of arthralgias, and reduce steroid intake. Adverse events were more frequent in our patients than has been reported in controlled studies for rheumatoid arthritis but corresponded to those found in post-marketing studies.
17331230 The funding and use of high-cost medicines in Australia: the example of anti-rheumatic bio 2007 Mar 1 BACKGROUND: Subsidised access to high-cost medicines in Australia is restricted under national programs (the Pharmaceutical Benefits Scheme, PBS, and the Repatriation Pharmaceutical Benefits Scheme, RPBS) with a view to achieving cost-effective use. The aim of this study was to examine the use and associated government cost of biological agents for treating rheumatoid arthritis over the first two years of subsidy, and to compare these data to the predicted outcomes. METHODS: National prescription and expenditure data for the biologicals, etanercept, infliximab, adalimumab, and anakinra were collected and analysed for the period August 2003 to July 2005. Dispensing data on biologicals sorted by the metropolitan, rural and remote zones and by prescriber major specialty were also examined. RESULTS: A total of 27,970 prescriptions for biologicals was reimbursed. The government expenditure was A$53.1 million, representing only 19% of that expected. Almost all prescriptions were reimbursed by the PBS (98%, A$52 million) and the remainder by the RPBS. Approximately 62% of the prescriptions were for concessional patients (A$32.9 million). There was considerable variability in the use of biologicals across Australian states and territories, usage roughly correlating with the per capita adjusted number of rheumatologists. The total number of prescriptions continued to increase over the study period. Etanercept was the most highly prescribed agent (74% by number of prescriptions), although its use was beginning to plateau. Use of adalimumab increased steadily. Use of infliximab and anakinra was considerably lower. The resultant health outcomes for individual patients are unknown. Prescribers from capital cities and other metropolitan centres provided a majority of prescriptions of biologicals (89%). CONCLUSION: The overall uptake of biologicals for treating rheumatoid arthritis over the first two years of PBS subsidy was considerably lower than expected. Long-term safety concerns and the expanded clinical uses of these drugs emphasise the need for evaluation. It is essential that there is comprehensive, ongoing analysis of utilisation data, associated expenditure and, importantly, patient outcomes in order to enhance accountability, efficiency and equity of policies that allocate substantial resources to subsidising national access to high-cost medicines.