Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16806940 Pyrexia following total knee replacement. 2006 Aug This study aims to determine the incidence and factors associated with pyrexia following total knee replacement (TKR). We performed a retrospective analysis of the temperature charts and histories of patients who underwent 170 TKRs. There was a statistically significant increase in mean temperature from pre-operation to post-operation, and this increase remained significant through to 5 days post surgery (p<0.0001). Sixty-two (36.5%) patients were pyrexial (>or=38 degrees C) at some point. Fourteen patients developed a clinical infection, but only four of these were pyrexial. There was no association between pyrexia and infection, allogenic blood transfusion, haemoglobin loss, use of urinary catheter, rheumatoid arthritis, anaesthetic type, and previous pyrexia following TKR. Pyrexia as a diagnostic test for the development of infection had a sensitivity of 0.286 (95% CI=0.084-0.581), specificity of 0.628 (95% CI=0.548-0.704) and positive predictive value of 0.065 (95% CI=0.018-0.157). Pyrexia in the first 5 days following TKR is usually a normal physiological response and should not cause undue concern about the presence of infection.
16736418 SAA1 alpha/alpha alleles in amyloidosis. 2006 Mar BACKGROUND: Amyloidosis, mainly AA type, is one of the common diseases in nephrology clinics in Turkey. AA type amyloidosis is a complication of various chronic infections or inflammatory diseases such as familial Mediterranean fever (FMF), rheumatoid arthritis (RA), tuberculosis and bronchiectasis. A controversy exists in the literature regarding the relationship between SAA1 genotypes and AA type amyloidosis. This study aimed to investigate SAA1 gene polymorphism in different patient groups: 1) amyloidosis, 2) FMF and 3) healthy controls. METHODS: Eighty-two patients from the three groups were included in the study: 1) amyloidosis, 2) FMF without amyloidosis, and 3) healthy controls. SAA1 genotypes were studied by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The homozygous alpha/alpha genotype is the most common SAA1 genotype among patient groups with amyloidosis, and the alpha/alpha genotype frequency is significantly higher than in healthy controls (68 vs. 38%, p<0.05). CONCLUSIONS: The SAA1 alpha/alpha genotype is a risk factor for AA type amyloidosis in Caucasoid populations and more studies are needed to investigate why the gamma/gamma genotype is associated with AA type amyloidosis in Japan.
16724943 Anti-oxidant gene therapy by NF kappa B decoy oligodeoxynucleotide. 2006 Apr Oxidative stress to cardiovascular cells induced by an interaction of multiple cytokines and adhesion molecules has been postulated to be responsible for cardiovascular disease. Since nuclear factor-kappaB (NFkappaB) also plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes, we utilized oligodeoxynucleotides (ODNs) as "decoy" cis-elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation. Indeed, transfection of NFkappaB decoy ODNs into coronary artery effectively prevented transactivation of essential cytokine and adhesion molecule protein expression, and thereby protected the myocardium from infarction. Transfection of NFkappaB decoy ODNs into balloon-injured carotid artery or porcine coronary artery markedly reduced neointimal formation. Thus, a clinical trial using NFkappaB decoy ODNs to treat restenosis was started in 2002. Recently, the therapeutic target utilizing NFkappaB decoy has been expanded to glomerulonephritis, rheumatoid arthritis, atopic dermatitis and osteoporosis. Moreover, the clinical trials to treat RA patients were initiated in 2003 and a Phase I/IIa human clinical trial using NFkappaB decoy ODNs to treat atopic dermatitis was initiated in December 2001. Topical application of NFkappaB decoy ODNs exhibited marked therapeutic effects on the facial skin condition of patients with atopic dermatitis. The covalently modified ODNs were developed by enzymatically ligating two identical molecules, thereby preventing their degradation by exonucleases. Indeed, the modified decoy ODNs possess increased nuclease resistance and are transported more efficiently into cells. Although there are still unresolved issues, decoy ODN drugs should become a reality.
16515469 Screening methods for antioxidants-a review. 2006 Mar Various environmental, physical and chemical stresses on cells may induce either an overproduction of ROS (Reactive Oxygen Species) or a deficiency of antioxidant enzymes. ROS are responsible for various cellular anomalies like protein damage, deactivation of enzymes, alteration of DNA and lipid peroxidation which in turn leads to pathological conditions like carcinogenesis, reperfusion injury, rheumatoid arthritis, diabetes etc. The regular intake of antioxidants seems to limit or prevent the dangerous effects caused by ROS. Thus, to maintain cellular health, it is important to have a specific and effective antioxidant that scavenges multiple types of free radicals so that it can be used in multiple diseases. Different in vitro and in vivo test systems are available in the literature to assess the free radical scavenging activity of various compounds. Based on the efficiency of free radical scavenging, the compounds are classified into strong, moderate and weak antioxidants. The following review explains the brief procedure and the principle behind various methods available in the literature, which can be used to determine the scavenging of different types of free radicals.
16467313 Factor structure of the child health questionnaire-parent form in pediatric populations. 2006 Mar OBJECTIVE: To conduct separate exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) of the Child Health Questionnaire-Parent Form 50 (CHQ-PF-50) with a sample of children and adolescents with chronic conditions and physically healthy children seen in a pediatric setting. METHOD: Parents of 329 children with chronic conditions including cancer, epilepsy, recurrent headache, inflammatory bowel disease (IBD), juvenile rheumatoid arthritis (JRA), sickle cell disease (SCD), and recurrent sleep disturbance and 332 physically healthy children completed CHQ-PF-50. RESULTS: The EFA yielded a 27-item measure with seven factors for children with chronic conditions and a 28-item measure with eight factors for physically healthy children. Structural equation modeling procedures were used to conduct a second order CFA, which yielded the secondary factors of physical health and psychosocial health. A CFA yielded an excellent fit to the data for each group, but the models were different for each group. CONCLUSIONS: CFA-derived models of the CHQ-PF-50 demonstrated construct validity for measuring the latent constructs of physical and psychosocial health in children and adolescents with chronic conditions and physically healthy children and adolescents. However, somewhat different factor solutions emerged for each group, suggesting that the specific domains assessed by the CHQ-PF-50 were not equivalent across groups. Findings have implications for applications of the CHQ-PF-50.
16449368 Current provision of rheumatology education for undergraduate nursing, occupational therap 2006 Jul OBJECTIVES: Rheumatological conditions are common and all health professionals (HPs) therefore need sufficient knowledge and skills to manage patients safely and effectively. The aim of this study was to examine current undergraduate education in rheumatology for HPs in the UK. METHODS: A questionnaire was sent to curriculum organizers and clinical placement officers for all undergraduate courses in adult nursing, occupational therapy (OT) and physiotherapy (PT) in the UK to ascertain the nature and amount of rheumatology theory and clinical exposure provided. RESULTS: Of the 47 adult nursing, 26 OT and 30 PT undergraduate courses surveyed, 85-90% responded. Overall, rheumatology teaching is 5-10 h over 3 yr. Nursing students receive moderate/in-depth teaching on rheumatoid arthritis (RA) in only 52% of courses (OT 91%, PT 96%) and on osteoarthritis (OA) in 63% (OT 91%, PT 92%). Clinical experience of RA is probably/definitely available in only 56% of nursing courses (OT 72%, PT 88%), with similar results in OA. Overall, nursing students receive the least rheumatology exposure, particularly in psychosocial issues and symptom management, while PT students receive the most. OT students have limited opportunities for clinical exposure to psychosocial and joint protection issues. Use of local rheumatology clinical HP experts is variable (18-93%) and cross-disciplinary exposure is limited (0-36%). Many educators consider their rheumatology training to be insufficient (nursing 50%, PT 42%, OT 24%). CONCLUSIONS: Rheumatology training for undergraduate HPs is limited in key areas and often fails to take advantage of local clinical expertise, with nursing students particularly restricted. Clinical HP experts should consider novel methods of addressing these shortfalls within the limited curriculum time available.
16397778 An unusual patient with kidney stones composed of 1-methyluric acid. 2006 Feb An unusual case with kidney stones composed mainly of 1-methyluric acid is described. The patient, a Caucasian male of Celtic descent, reportedly drank at least eight cups of coffee per day and had a long history of rheumatoid arthritis, gouty attacks and renal colics--the latter attributed to nephrocalcinosis and analgesic nephropathy. He was treated with allopurinol. At 54 years, a bilateral nephrolithotomy was performed. Stone samples were analysed by thermogravimetry and infrared spectroscopy and reported to be 12-25% calcium oxalate, the remainder being organic uric acid-like material. Analysis of the extracts by HPLC confirmed that the organic material contained 67% of 1-methyluric acid and 33% of uric acid. Possible mechanisms leading to the precipitation of 1-methyluric acid from urine are discussed. We conclude that the high caffeine intake resulted in extremely elevated urinary concentrations of 1-methyluric acid favouring the formation of 1-methyluric acid stones.
16370952 Toxicity of infliximab in the course of treatment of Crohn's disease. 2006 Jan Infliximab is a monoclonal antibody directed against the pro-inflammatory mediator TNF-alpha, which was approved in the US in 1998 for treatment-resistant Crohn's disease. Since that time, the indications have dramatically expanded to include rheumatoid arthritis, ankylosing spondylitis, psoriasis and most recently, active ulcerative colitis. Although the safety profile in the initial studies was quite favourable, subsequent studies have shown that a small percentage of patients reported severe side effects, including pneumonia, tuberculosis, lymphoma, drug-induced lupus and hepatotoxicity. Although these complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment. Furthermore, concurrent use of other immunosuppresive agents, such as 6-mercaptopurine, may reduce the incidence of less serious side effects, such as arthralgias, myopathies and other antibody-associated diseases. Since its approval, infliximab has revolutionised the treatment of Crohn's disease and has shown benefit in a variety of other inflammatory conditions, but significant toxicities can occur that necessitate thorough screening protocols and periodic clinical evaluation.
16305742 Recent developments in targeting access to high cost medicines in Australia. 2005 Nov 23 BACKGROUND: In Australia, the Pharmaceutical Benefits Scheme (PBS) has developed a set of arrangements to control access to high-cost medicines to ensure their use is cost-effective. These medicines include the tumour necrosis factor-alpha inhibitors (TNFIs) for the treatment of rheumatoid arthritis. The aim of this first phase of a qualitative study was to explore basic views on the restricted access to TNFIs in order to confirm where further investigation should take place in the next phase. METHODS: Semi-structured interviews were conducted in 2004 with a member of the four relevant stakeholder groups. Participants were asked their opinions about features of the establishment, process and effects of the system of restricted access to TNFIs. Views on the collaboration between stakeholder groups in the decision-making process were also collected. RESULTS: The principle of 'controlled access' to TNFIs was supported in general. There were concerns regarding some of the specific eligibility criteria. Wider and more transparent stakeholder consultation was judged desirable. Some flexibility around prescribing of TNFIs by physicians, and regular review of the arrangements were proposed. These themes will inform the next phase of the study. CONCLUSION: This first phase highlighted a range of issues associated with the PBS arrangements restricting access to TNFIs. Timely review and report of issues and concerns associated with such policy developments that arose in practice are essential. There is a need for a more comprehensive exploration across a wide range of stakeholders with different perspectives that will in turn be helpful in guiding policy and practice around national arrangements to manage access to high-cost medicines.
16242914 BAFF is elevated in serum of patients with Wegener's granulomatosis. 2005 Dec BAFF (B-cell activating factor of the TNF family) plays a crucial role in B-cell survival. Elevated BAFF serum levels have been linked to several autoimmune diseases in humans, and therapies targeting BAFF were successful in animal models of rheumatoid arthritis and systemic lupus erythematosus. Wagener's granulomatosis (WG), a chronic systemic vasculitis, is characterized by circulating autoantibodies (cANCA) targeting neutrophils, which can produce BAFF. To investigate whether BAFF is involved in WG pathology, BAFF serum levels were measured by ELISA in 46 WG patients and 62 healthy donors. We report the novel finding that in WG patients serum levels of BAFF were significantly increased (median 3.95 ng/ml, p=0.009) compared to healthy controls (median 2.38 ng/ml). The difference was even more pronounced when comparing controls with untreated WG patients (median 4.61 ng/ml, p=0.001). Treatment of WG patients with glucocorticoids was associated with lower BAFF levels. The serum BAFF level in treated WG patients was about the same as in the control group. We propose that BAFF might be a pathogenic factor in WG and that targeting BAFF may represent a new therapeutic strategy in a subset of chronically relapsing WG patients with elevated BAFF levels.
16178727 Structure-activity relationships of p38 mitogen-activated protein kinase inhibitors. 2005 Sep Rheumatoid arthritis and other chronic inflammatory diseases constitute a major therapeutic challenge, usually not sufficiently met by the classical antiinflammatory medications. Recent research efforts provided new insights into the molecular basis of these pathologies and disclosed new opportunities for developing improved drugs directed to the chemical mediators of the disease. The enzyme p38 MAP kinase plays a central role in the signal transduction cascade that leads to the production of both the proinflammatory cytokines, TNF-alpha and IL-1 beta, thus representing an attractive therapeutic target for novel antiinflammatory therapies. A number of p38 inhibitors belonging to different structural families have been developed as potential antiinflammatory drugs, and some of them progressed into clinical trials. The initial pyridinyl imidazole inhibitors contributed to the identification and characterization of p38 MAP kinase as the molecular target of these new drugs, and were found to act as competitive inhibitors at the ATP binding site of the enzyme. A number of variations in the pyridine and imidazole rings were subsequently introduced. Other inhibitors structurally unrelated to the pyridinylimidazoles have also been developed, such as the pyridopyridazinones, diaryl ureas, aminobenzophenones and aromatic amides. One of these structural classes, the N,N'-diarylureas, has been found to interact with a distinct allosteric site of p38 MAP kinase and requires a deep conformational change prior to binding.
16051095 Odontoid compression of the brainstem without basilar impression-- "odontoid invagination" 2005 Jun We report five patients with odontoid invagination, in which the odontoid process bulges upward into the foramen magnum and compresses the brainstem without deformity of the occipital bone. Two patients had a craniovertebral abnormality associated with Chiari malformation without instability of the craniovertebral junction (stable odontoid invagination). The other three patients had dislocation of the craniovertebral junction due to iatrogenic destruction of the occipital condyle, rheumatoid arthritis or an anomaly of C2 (unstable odontoid invagination). Patients with stable odontoid invagination underwent a transoral odontoidectomy followed by occipitocervical fixation. Those with unstable odontoid invagination underwent cervical traction followed by posterior fixation in reducible cases, while in irreducible cases odontoidectomy with subsequent occipitocervical fixation was performed. Decompression of the neuraxis together with symptomatic improvement was achieved in all patients and none became unstable or developed new symptoms during follow-up ranging from 3 to 15 years.
15913508 Infliximab: Use in Inflammatory Bowel Disease. 2005 Jun Crohn's disease (CD) and ulcerative colitis (UC) are chronic and often debilitating inflammatory bowel diseases (IBD) without medical cures. Despite the existence of multiple therapies, the medical treatment of these diseases often has proven insufficient and surgery is frequently required. However, as our understanding of the pathogenesis of these disorders and other immune-mediated inflammatory diseases (eg, rheumatoid arthritis and psoriasis) has grown, new and more specific biologic therapies have been developed that are proving more effective than traditional agents. Infliximab is a genetically engineered monoclonal antibody that targets the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and represents the first effective biologic therapy for IBD and has largely revolutionized treatment. Infliximab initially was developed to be used in patients with moderate to severe luminal or fistulizing CD who are refractory to standard medical therapy. More and more practitioners now are using infliximab as first-line therapy because of its superior efficacy. Infliximab rapidly induces remission in CD, but when given chronically, it can provide long-term maintenance of remission. In addition, there are some data to support its use as a steroid-sparing agent and treatment for various extraintestinal manifestations of IBD and, although used predominantly to treat CD, recent data suggest that infliximab also may have a role in the management of UC. Overall, infliximab represents a clinically useful, cost-effective therapy that works well, even though careful patient monitoring is required to avoid rare but significant toxicities. The hope is that infliximab, together with other biologic agents that currently are in development, will allow us to modify the course of IBD, avoid complications such as strictures and abscesses, and reduce the need for surgery.
15761461 Fever of unknown origin: subacute thyroiditis versus typhoid fever. 2005 Mar Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings.
15700232 Determination of sites citrullinated by peptidylarginine deiminase using 18O stable isotop 2005 Peptidylarginine deiminase (PADI) is an enzyme which catalyzes conversion of arginine residues into citrulline residues in proteins. Citrullination is known to be related to autoimmune diseases including rheumatoid arthritis. Previous work in this laboratory succeeded in identifying citrullinated sites of human fibrinogen by mass spectrometry, but discrimination between citrullination and deamidation of asparagines and glutamine required time-consuming and labor-intensive inspection of tandem mass spectra. In this work a stable isotope is utilized to improve on a previous method for the determination of citrullinated sites by mass spectrometry. Since an oxygen atom is incorporated into the citrulline residue from H(2)O in citrullination by PADI, peptides citrullinated in 50% H(2)(18)O would show a characteristic isotope distribution different from natural abundance, and thus determination of citrullinated sites is expected to be much easier. To verify the utility of this new method, the sites of citrullination of human fibrinogen by human PADI4 were investigated using 50% H(2)(18)O. Compared with the previous method, this new method identified citrullinated sites more easily and effectively, while both the determined citrullinated sites and protein sequence coverage were unaltered.
15651713 Efficacy of lumiracoxib in osteoarthritis: a review of nine studies. 2005 Jan Lumiracoxib is a cyclooxygenase-2 selective inhibitor in development for the treatment of osteoarthritis (OA), rheumatoid arthritis and acute pain. We reviewed nine clinical studies of 1-52 weeks' duration demonstrating the efficacy of lumiracoxib in OA. Male and female patients aged > or = 18 years with primary OA of the hand, hip or knee received lumiracoxib, placebo or active comparators (diclofenac, celecoxib or rofecoxib). Lumiracoxib provided consistent reductions in OA pain intensity and improvements in the patient's global assessment of disease activity and functional status (assessed using the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire or the Australian/Canadian OA Hand Index). These results were superior to placebo and similar to the active comparators tested. In addition, lumiracoxib was consistently superior to placebo and generally similar to active comparators in terms of the new Outcome Measures in Clinical Trials and Osteoarthritis Research Society International criteria. These were used to provide a single measure of response to treatment, taking into account pain, the patient's global assessment of disease activity and functional status.
17946924 Development of a finger joint phantom for evaluation of frequency domain measurement syste 2006 For development and test of new optical imaging devices, phantoms are widely used to emulate the tissue to be imaged. Phantom design gets more difficult the more complex the tissue is structured. We report on developing and testing a solid, stable finger joint phantom to simulate transillumination of finger joints in frequency-domain imaging systems. The phantom consists of the bone, capsule, skin, the capsule volume, and the joint gap. Silicone was used to build the solid parts and a glycerol-water solution for the fluid in the capsule volume and joint gap. The system to test the phantom is an optical frequency-domain scanning set-up. Different stages of joint inflammation as they occur in rheumatoid arthritis (BA) were emulated by assembling the phantom with capsule and fluid having different optical properties. Reliability of the phantom measurement was investigated by repeated assembling. The results show clear discrimination between different stages of joints within the signal deviation due to reassembling of the phantom.
17191007 Osteoimmunology. 2007 Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor kappaB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.
17121493 Osteoporosis: is there a rational approach to fracture prevention? 2006 The most effective way to manage osteoporosis is to prevent fractures before they occur. To do this, a clinician needs to be aware of both the clinical risk factors that predispose a patient to an osteoporotic fracture and the patient's bone mineral density (BMD). An assessment of risk factors that increase fracture risk, including age, weight less than 125 pounds as an adult, family history of hip fracture, low-impact fractures as an adult, inability to rise up from a chair without using one's arms, presence of rheumatoid arthritis (RA), and use of glucocorticoid medication, in addition to low BMD, is necessary to assess fracture risk. Therefore, a complete history and BMD will improve the identification and treatment of patients at high risk of an osteoporotic fracture. Also, patients with systemic inflammatory diseases like RA or systemic lupus erythematosus have an increased risk of fracture owing to systemic inflammation independent of glucocorticoid use. These patients should be screened for osteoporotic risk factors, and BMD tests should be obtained. Treatment to prevent fractures should be initiated at a BMD (T score) <-1 to improve skeletal health in these patients. This review provides an update on the epidemiology of fractures, reviews fracture risk-factor assessment, and makes recommendations on how to screen patients and decide which patients would benefit from an intervention. Lastly, this review analyzes the new initiative by the World Health Organization (WHO) to assess fracture risk and new information on assessment of bone health in rheumatic disease patients.
17110309 Possible pathogenic nature of the recently discovered TT virus: does it play a role in aut 2006 Nov Pathogenesis of viral origin has long been suggested in autoimmune rheumatic diseases. Beside the well-defined virus induced transient or chronic rheumatic diseases often resembling systemic autoimmune disorders such as rheumatoid arthritis, viruses can contribute to disease pathogenesis by several different pathomechanisms. TT virus is a recently discovered virus of extremely high genetic diversity which commonly infects humans. Despite accumulated evidence on the biological characteristics of TTV, its pathogenicity is still in question; many consider TTV as a harmless endosymbiont. The recent paper overviews the biology of TT virus and investigates the hypothesis that TTV might have a causative role in human diseases with special attention to the possibility that TTV might trigger autoimmunity in rheumatic disorders.