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ID PMID Title PublicationDate abstract
12114283 Melatonin in rheumatoid arthritis: synovial macrophages show melatonin receptors. 2002 Jun The pineal neurohormone melatonin is widely recognized as exerting important immunoenhancing effects that act on specific receptors in immunocompetent cells. This action results in stimulation of cytokine production in lymphocytes and macrophages. Here we report that the nocturnal plasma concentration of melatonin in rheumatoid arthritis (RA) patients is higher than in healthy controls. Furthermore, melatonin is present in the synovial fluid of RA patients and synovial macrophages express a specific binding site. We suggest that melatonin may exert a disease-promoting role in RA.
15458959 Raised levels of anti-glucose-6-phosphate isomerase IgG in serum and synovial fluid from p 2005 May BACKGROUND: In K/BxN mice, anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are arthritogenic, and their transfer into naive mice induces arthritis. Anti-GPI Abs develop in many human patients with RA and are associated with more severe forms of the disease. OBJECTIVE: To elucidate the serum and synovial fluid (SF) anti-GPI IgG profiles among different patient groups with a variety of arthritides. METHODS: Blood and SF obtained concomitantly from 91 patients with clinically well defined arthritis were tested for concentrations of total anti-GPI IgG, anti-GPI IgG subclasses, B lymphocyte stimulator (BLyS), and APRIL by ELISA. RESULTS: Anti-GPI IgG was detected in sera and SF of patients with many arthritic diseases, but was preferentially associated with inflammatory arthritis, in general, and RA, in particular. The anti-GPI IgG subclass usage was skewed and varied among the different arthritic disease groups. Inverse correlations between serum levels of BLyS and anti-GPI IgG and positive correlations between serum levels of APRIL and anti-GPI IgG were seen among immune based arthritic patients and patients with RA but not among non-immune based patients. No correlations were found in SF from any group of arthritic patients. CONCLUSION: Raised circulating anti-GPI Abs are not unique to patients with RA but are present in many patients with inflammatory arthritis. The difference in anti-GPI IgG subclass usage among disease groups may influence effector function and disease outcome. The inverse correlation between serum BLyS and anti-GPI IgG levels suggests that anti-GPI B cells may be regulated differently from other autoantibody producing B cells. Anti-GPI Abs may serve a pathogenic function in humans by promoting the maintenance of existing disease.
12375239 Factors associated with excessive migration in bone impaction hip revision surgery: a radi 2002 Oct A prospective radiostereometric analysis (RSA) study of 18 patients with cemented revision hip surgery and impaction grafting with an Exeter stem was done with a follow-up of 2 years for all patients. All factors that could influence migration (ie, micromotion) of the stem were analyzed with a repeated measurements analysis of variance. Two groups could be identified: a stable group and a continuous migrating group. Two factors significantly influenced micromotion during the follow-up measurements. The first factor was the Paprosky classification (the bigger the defect, the higher the micromotion). The second factor was cement mantle defects in > or =1 Gruen zones. The migrating hip stems had more Gruen zones with cement mantle defects (45%) compared with the stable prostheses (21%). The effect of the first factor on micromotion was limited and probably clinically less relevant. Because the cement mantle defects found in this study were caused by poor instrumentation, the second factor stresses the importance of good instrumentation, which is essential to make this technically demanding technique effective in creating a stable stem-allograft construct in the defective femoral canal.
12097415 Characterization of autoreactive T cells to the autoantigens heterogeneous nuclear ribonuc 2002 Jul 15 The role of autoimmune reactions in the pathogenesis of rheumatoid arthritis (RA) is poorly understood. To address this issue we have investigated the spontaneous T cell response to two well-characterized humoral autoantigens in RA patients and controls: 1) the heterogeneous nuclear ribonucleoprotein A2, i.e., the RA33 Ag (A2/RA33), and 2) filaggrin in unmodified and citrullinated forms. In stimulation assays A2/RA33 induced proliferative responses in PBMC of almost 60% of the RA patients but in only 20% of the controls (patients with osteoarthritis or psoriatic arthritis and healthy individuals), with substantially stronger responses in RA patients (p < 0.00002). Furthermore, synovial T cells of seven RA patients investigated were also clearly responsive. In contrast, responses to filaggrin were rarely observed and did not differ between RA patients and controls. Analysis of A2/RA33-induced cytokine secretion revealed high IFN-gamma and low IL-4 production in both RA and control PBMC, whereas IL-2 production was mainly observed in RA PBMC (p < 0.03). Moreover, A2/RA33-specific T cell clones from RA patients showed a strong Th1 phenotype and secreted higher amounts of IFN-gamma than Th1 clones from controls (p < 0.04). Inhibition experiments performed with mAbs against MHC class II molecules showed A2/RA33-induced T cell responses to be largely HLA-DR restricted. Finally, immunohistochemical analyses revealed pronounced overexpression of A2/RA33 in synovial tissue of RA patients. Taken together, the presence of autoreactive Th1-like cells in RA patients in conjunction with synovial overexpression of A2/RA33 may indicate potential involvement of this autoantigen in the pathogenesis of RA.
14561164 IL-6 and Crohn's disease. 2003 Jun Interleukin-6 (IL-6) is a pleiotropic cytokine with central roles in immune regulation, inflammation, hematopoiesis, and oncogenesis. Its biological activities are shared by IL-6-family of cytokines such as leukemia inhibitory factor and oncostatin M. When IL-6 binds to IL-6R, the IL-6/IL-6R complex then associates with gp130, the common signal transducer of cytokines related to IL-6. IL-6R does not have to be expressed on the cell surface for IL-6 signaling because soluble form of IL-6R (sIL-6R) can bind to IL-6 and function through gp130. Increased levels of IL-6 and sIL-6R have been demonstrated in both serum and intestinal tissues of the patients with active Crohn's disease. In animal model studies, anti-IL-6R monoclonal antibody (mAb) successfully prevented intestinal inflammation and systemic wasting disease by suppressing adhesion molecule expression by vascular endothelium. It also reduced colonic expression of tumor necrosis factor alpha, IL-1beta, and interferon gamma mRNA without affecting the production of transforming growth factor beta, IL-10, and IL-4. Moreover, the treatment displayed therapeutic efficacy against established colitis through the induction of lamina propria T-cell apoptosis. These results strongly suggest that specific targeting of IL-6/sIL-6R pathway will be a promising new approach for the treatment of Crohn's disease, and the clinical trial of humanized anti-IL-6R mAb has been carried out.
11954009 Value of laboratory tests in early prediction of rheumatoid arthritis. 2002 Apr 15 OBJECTIVE: To determine which laboratory test or tests at presentation best predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: Two hundred seventy patients with early arthritis seen in 7 hospitals underwent comprehensive evaluations at 6-month intervals for 2 years, when the diagnosis of RA was assessed by 5 rheumatologists. The sensitivity and specificity of each test at the first visit for discriminating between RA (38%, n = 98) and non-RA patients were determined. Optimal cutoffs for continuous tests were derived from receiver operating characteristic curves. Sensitivity and specificity of test combinations selected by multiple logistic regression were determined. RESULTS: IgM rheumatoid factor (RF) by enzyme-linked immunosorbent assay, IgG-antikeratin antibody (AKA), and latex test had the strongest associations with RA. These 3 tests formed the most powerful combination for distinguishing RA from non-RA. CONCLUSION: IgM-RF, IgG-AKA, and the latex test are the best laboratory tests for discriminating between patients with and without RA. Combining these tests slightly improves diagnostic value.
11966773 Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of 2002 Mar Interleukin-17 (IL-17) has been characterized as a proinflammatory cytokine produced by CD4+ CD45RO+ memory T cells. Overproduction of IL-17 was detected in the synovium of patients with rheumatoid arthritis (RA) compared to patients with osteoarthritis. In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R/CDw217) is expressed ubiquitously. Using a real-time RT-PCR assay, we detected similar absolute levels of IL-17R mRNA expression in fibroblast-like synoviocytes (SFC) from patients with RA (mean 9 pg/microg total RNA; ranged from 0.1 pg to 96 pg IL-17R mRNA/microg total RNA) compared to synoviocytes of non-RA patients. Analysis of the IL-17R surface expression confirmed the results obtained for IL-17R mRNA expression. Exposure of SFC to IL-17 led to a mRNA induction of CXC chemokines IL-8, GRO-alpha and GRO-beta. An anti-IL-17 antibody blocked these effects of IL-17. The MAPK p38 appears necessary for the regulation of IL-8, GRO-alpha and GRO-beta expression as shown by inhibition with SB203580. The inhibitors genistein (tyrosine kinase inhibitor) and calphostin C (inhibitor of protein kinase C) reduced significantly the IL-17-stimulated mRNA expression of IL-8, GRO-alpha and GRO-beta in SFC, whereas PD98059 (inhibitor of MEK-1/2) was without effect. Pharmacological drugs used in therapy of RA, such as cyclosporin and methotrexate, induced a fourfold increase of IL-17R mRNA expression and augmented the IL-17-stimulated IL-8 expression. Our results support the hypothesis that IL-17/IL-17R may play a significant role in the pathogenesis of RA contributing to an unbalanced production of cytokines as well as participating in connective tissue remodelling.
12468815 The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMAR 2002 Dec BACKGROUND: Therapy of rheumatoid arthritis (RA) is typically characterized by the sequential use of disease-modifying anti-rheumatic drugs (DMARDs). This study aimed to reveal treatment patterns with traditional DMARDs and their changes during the two decades before the recent introduction of new DMARDs. METHODS: A total of 593 RA patients were followed from their first presentation to our clinic throughout the course of their disease; 222 patients received their first DMARD therapy while under our care. More than 2,300 patient years of therapy were analysed for the efficacy [using C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as surrogates] and duration of drug therapy of consecutive DMARDs. RESULTS: Before 1985, 65-90% of initial DMARDs were gold compounds, but their use decreased continuously thereafter. Antimalarial (AM) drugs were important initial DMARDs in new patients at all times, whereas sulphasalazine (SSZ) and methotrexate (MTX) gained increasing significance after 1985 (the first DMARD was MTX in up to 29% of new patients). Penicillamine (DPA), azathioprine (AZP), cyclosporin (CyA) and combination therapies were not usually employed initially, but were reserved for the later course of the disease. Gender, age and rheumatoid factor were not different between patients receiving different DMARDs. The baseline acute-phase response was higher in patients treated with MTX (mean CRP 3.5 mg/dl) than in those treated with SSZ (CRP 2.4 mg/dl; P < 0.05) or AM (CRP 2.1 mg/dl; P < 0.05), suggesting that MTX was used preferentially in patients with high disease activity. On the other hand, once AM or SSZ had been discontinued, MTX was the most common subsequent DMARD (in 31 and 56% respectively). Comparison of first DMARDs with subsequent ones revealed that first DMARDs were more effective: the acute-phase response decreased most prominently during first therapies (CRP reduction was 1.28 mg/dl during first courses and 0.35 mg/dl during fourth or later courses; P < 0.01); and retention rates were significantly longer for first compared with subsequent therapies (median of 24.5 months for first and 18.6 months for fourth or subsequent therapies; P < 0.001). CONCLUSION: MTX was the most commonly employed DMARD therapy for RA and was used increasingly as first therapy in newly diagnosed RA. Patients with high disease activity were given MTX therapy more often than other DMARDs, while those with low activity were more likely to receive SSZ or AM, and MTX on failure of these drugs. First DMARDs in new patients were retained longer than subsequent DMARDs, apparently because they are more effective.
11954010 Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia o 2002 Apr 15 OBJECTIVES: We have investigated in vitro erythroblast iron metabolism in the anemia of rheumatoid arthritis (RA). We also have examined the results in relation to bone marrow iron status in an attempt to explain the reported difference between serum soluble transferrin receptor (sTfR) values in anemia of chronic disease (ACD) and iron deficiency anemia (IDA) in patients with RA. METHODS: Bone marrow was examined in 29 anemic patients with RA, 9 healthy volunteers, and 6 patients with simple IDA. High purity erythroblast fractions were prepared from these bone marrow samples. Erythroblast surface TfR expression and iron uptake was assessed in vitro using (125)I-transferrin (Tf) and (59)Fe-Tf, respectively. The efficiency of erythroblast surface TfR function for Tf-iron uptake was determined by relating total iron uptake at 4 hours to surface TfR number. Serum sTfR values were measured for the RA anemia group, which was subdivided as RA-ACD (marrow iron present) or RA-IDA (marrow iron absent) on the basis of visible reticuloendothelial (RE) marrow iron stores. RESULTS: High purity (87 +/- 5%) erythroblast fractions were obtained from 35 of the 44 marrow samples. Erythroblasts obtained from patients with simple IDA showed a significant increase in surface TfR expression (P = 0.0003) and Tf-iron uptake (P = 0.001). RA anemia also led to a significant increase in erythroblast Tf-iron uptake (P = 0.016). This increase was not associated with an increase in surface TfR expression (P = 0.5), but was seen to occur as a result of a significant increase in the efficiency of surface TfR for Tf-iron uptake (P = 0.027). Within the RA anemia group, the increase in erythroblast Tf- iron uptake at 4 hours was more evident for RA-IDA (3.96 +/- 1.73 versus 1.66 +/- 0.66; P = 0.03) than for RA-ACD (2.69 +/- 1.18 versus 1.66 +/- 0.66; P = 0.057). This additional erythroblast response to absent RE iron stores led to a highly significant difference in serum sTfR values between RA-IDA and RA-ACD (40.2 +/- 14.0 versus 23.9 +/- 5.3 nmoles/liter; P = 0.001) CONCLUSIONS: An increase in erythroblast surface TfR efficiency for Tf-iron uptake compensates for the low plasma iron levels associated with anemia in RA and helps to maintain RA erythroblast iron uptake. With adequate RE iron stores, this increased efficiency limits intracellular iron deprivation and consequently reduces the need to increase surface TfR expression. As a result, serum sTfR levels in RA-ACD remain within the normal range. RA erythroblasts, however, are still able to respond to any additional worsening of the iron supply caused by absent RE iron stores. This additional response causes the highly significant increase in serum sTfR values seen between RA-IDA and RA-ACD.
14769514 Role for osteoprotegerin in rheumatoid inflammation. 2004 Jan Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-alpha, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA.
15320914 Diagnostic and prognostic values of anti glucose-6-phosphate isomerase antibodies in commu 2004 Sep The objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45.4%) compared to healthy subjects (2.5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45.4%, adult-onset Still's disease 44%, systemic sclerosis 42.8%, spondylarthropathies 25% and primary Sjögren's syndrome 5.8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.
14962955 Activation of the STAT1 pathway in rheumatoid arthritis. 2004 Mar BACKGROUND: Expression of signal transducer and activator of transcription 1 (STAT1), the mediator of interferon (IFN) signalling, is raised in synovial tissue (ST) from patients with rheumatoid arthritis (RA). OBJECTIVES: To determine the extent to which this pathway is activated by phosphorylation in RA synovium. Additionally, to investigate the cellular basis of STAT1 activation in RA ST. METHODS: ST specimens from 12 patients with RA and 14 disease controls (patients with osteoarthritis and reactive arthritis) were analysed by immunohistochemistry, using antibodies to STAT1, tyrosine phosphorylated STAT1, and serine phosphorylated STAT1. Lysates of cultured fibroblast-like synoviocytes stimulated with IFNbeta were analysed by western blotting. Phenotypic characterisation of cells expressing STAT1 in RA ST was performed by double immunolabelling for STAT1 and CD3, CD22, CD55, or CD68. RESULTS: Raised levels of total STAT1 protein and both its activated tyrosine and serine phosphorylated forms were seen in RA synovium as compared with controls. STAT1 was predominantly abundant in T and B lymphocytes in focal inflammatory infiltrates and in fibroblast-like synoviocytes in the intimal lining layer. Raised levels of STAT1 are sustained in cultured RA compared with OA fibroblast-like synoviocytes, and STAT1 serine and tyrosine phosphorylation is rapidly induced upon stimulation with IFNbeta. CONCLUSION: These results demonstrate activation of the STAT1 pathway in RA synovium by raised STAT1 protein expression and concomitantly increased tyrosine (701) and serine (727) phosphorylation. High expression of STAT1 is intrinsic to RA fibroblast-like synoviocytes in the intimal lining layer, whereas activation of the pathway by phosphorylation is an active process.
15208781 A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatas 2004 Aug Rheumatoid arthritis (RA) is the most common systemic autoimmune disease, affecting approximately 1% of the adult population worldwide, with an estimated heritability of 60%. To identify genes involved in RA susceptibility, we investigated the association between putative functional single-nucleotide polymorphisms (SNPs) and RA among white individuals by use of a case-control study design; a second sample was tested for replication. Here we report the association of RA susceptibility with the minor allele of a missense SNP in PTPN22 (discovery-study allelic P=6.6 x 10(-4); replication-study allelic P=5.6 x 10(-8)), which encodes a hematopoietic-specific protein tyrosine phosphatase also known as "Lyp." We show that the risk allele, which is present in approximately 17% of white individuals from the general population and in approximately 28% of white individuals with RA, disrupts the P1 proline-rich motif that is important for interaction with Csk, potentially altering these proteins' normal function as negative regulators of T-cell activation. The minor allele of this SNP recently was implicated in type 1 diabetes, suggesting that the variant phosphatase may increase overall reactivity of the immune system and may heighten an individual carrier's risk for autoimmune disease.
14730602 Retinoblastoma suppression of matrix metalloproteinase 1, but not interleukin-6, through a 2004 Jan OBJECTIVE: Rheumatoid arthritis (RA) is characterized by increased synovial lining cellularity, inflammation, and destruction of cartilage and bone. During the pathogenesis of RA, synovial fibroblasts reenter the cell cycle and multiply in number. RA synovial fibroblasts express high levels of the MAP kinase p38, which may contribute to the production of interleukin-6 (IL-6) and matrix metalloproteinases (MMPs). IL-6 and MMP-1 promote inflammation and joint destruction, respectively. Taken together, these findings indicate that in RA the enhanced cell cycle activity and production of IL-6 and MMP-1 may be linked. Therefore, we sought to determine if the tumor suppressor gene product retinoblastoma (Rb), a negative regulator of cell cycle activity, inhibits IL-6, MMP-1, and p38 in RA synovial fibroblasts. METHODS: RA and non-RA synovial fibroblasts were examined by enzyme-linked immunosorbent assay (ELISA) for the relative expression of inactive hyperphosphorylated Rb (inactive Rb/total Rb). Ectopic Rb expression was mediated by infection with a replication-defective adenovirus that expresses Rb (Ad-Rb). A control replication-defective adenovirus that expresses beta-galactosidase (Ad-beta-gal) was used. Cell cycle activity was determined by flow cytometry. IL-6 and MMP-1 expression was examined by real-time polymerase chain reaction and ELISA. Expression and activation of p38 were determined by kinase assays and ELISA. The activity of p38 was enhanced by infecting RA synovial fibroblasts with a replication-defective adenovirus that expresses a constitutively active form of MAPK kinase 3 (Ad-CA-MKK3), an upstream activator of p38. RESULTS: Quiescent RA, compared with non-RA synovial fibroblasts, displayed a 200% (P < 0.02) increase in the inactive Rb isoform. Proliferating RA synovial fibroblasts exhibited a 60% (P < 0.12) increase in the inactive Rb isoform compared with non-RA synovial fibroblasts. Increased levels of the active Rb isoform inhibited cell cycle progression and suppressed IL-6 and MMP-1 secretion in RA synovial fibroblasts, although the steady-state levels of IL-6 and MMP-1 messenger RNA remained unchanged. However, Rb overexpression had no effect on spontaneous or IL-1beta-induced production of IL-6 or MMP-1 in non-RA synovial fibroblasts. Ectopic Rb expression reduced the activity of p38. Ad-CA-MKK3 infection in RA synovial fibroblasts increased p38 phosphorylation, and MMP-1 but not IL-6 secretion. In contrast, Rb overexpression inhibited Ad-CA-MKK3-mediated phosphorylation of p38 and subsequent increase in MMP-1. CONCLUSION: Rb-mediated suppression of IL-6 and MMP-1 occurs at a posttranscriptional level. However, Ad-Rb reduction of MMP-1 but not IL-6 requires inhibition of the p38 pathway. These results suggest that Rb negatively regulates p38 activation, leading to decreased MMP-1 secretion in RA synovial fibroblasts.
12974768 Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis 2003 Oct Evidence suggests that spironolactone, an aldosterone antagonist, has effects on many cell types independent of its binding to cytosolic mineralocorticoid receptors. We tested the effects of spironolactone on ex vivo-activated human blood leucocytes using gene expression analyses (GeneChip, 12,000 genes) and enzyme immunoassay for quantitating secreted pro- and anti-inflammatory cytokines. Furthermore, to evaluate the safety and efficacy of spironolactone as an anti-inflammatory drug 21 patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) or other arthritides were treated for up to 22 months with 1-3 mg/kg/day. Spironolactone, at in vivo attainable doses, markedly suppressed transcription of several proinflammatory cytokines and, accordingly, inhibited release of tumour necrosis factor, lymphotoxin, interferon-gamma, granulocyte-macrophage colony-stimulating factor and interleukin 6 (70-90% inhibition). Release of these cytokines was also suppressed when testing whole blood from RA patients receiving 50 mg spironolactone twice daily, indicating that pharmaceutical use of the drug may suppress the release of inflammatory cytokines. Spironolactone therapy was generally well tolerated, although treatment had to be stopped in two adults on concomitant methotrexate therapy. Sixteen patients (76%) responded favourably. American College of Rheumatology criteria (ACR)20 or better was achieved in six of nine RA patients; four reached ACR70. Eight of nine JIA patients improved. In conclusion, spironolactone inhibits production of several proinflammatory cytokines considered to be of pathogenic importance in many immunoinflammatory diseases and shows positive effect in patients with chronic arthritis. Its effect as an anti-inflammatory drug should be explored, because prolonged spironolactone therapy is reasonably safe and economically attractive compared with many modern anti-inflammatory therapies.
11954005 Health outcomes assessment in community pharmacy practices: a feasibility project. 2002 Apr 15 OBJECTIVES: To evaluate the feasibility and benefit of capturing outcomes data in community pharmacy settings, and to characterize the health status, resource use, and medication use of patients with musculoskeletal disorders. METHODS: Patients (n = 460) with musculoskeletal disorders including osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain from 12 community pharmacy sites responded to disease-specific questions, the Medical Outcomes Study Short Form-36 (SF-36) health survey, demographics, and resource use using touch screen computer technology. Patients provided information and met with a community pharmacist for scheduled visits at baseline, 3, 6, 9, and 12 months. Pharmacists, with the aid of the patient-reported information, documented medication use and identified and addressed drug therapy problems of the patients at each visit. Baseline results, based on descriptive statistics are reported. RESULTS: OA was reported by 71% of the patients, 55% reported low back pain, and 19% reported RA. Despite receiving a variety of analgesic medications, a majority of the patients reported experiencing moderate to severe pain. SF-36 scores of the study population were significantly lower than age-adjusted population norms, with arthritis patients reporting worse physical health than patients with low back pain. Drug therapy problems were identified in 58% of the population, with need for additional drug therapy (31%) and adverse drug reactions (18%) being the most common problems identified. CONCLUSIONS: Results indicate that routine capture of patient-reported health outcomes data is feasible in community pharmacy settings using touch screen technology.
15196997 Autoimmune diseases and vaccinations. 2004 Mar The potential association between vaccination and autoimmune diseases has been largely questioned in the past few years, but this assumption has mostly been based on case reports. The available evidence derived from several negative epidemiological studies is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. However, there are still uncertainties as to whether a susceptible subpopulation may be at a higher risk of developing an autoimmune disease without causing an overall increase in the disease incidence. Based on selected examples, this review highlights the difficulties in assessing this issue. We suggest that a potential link between vaccines and autoimmune diseases cannot be definitely ruled out and should be carefully explored during the development of new candidate vaccines.
15244490 Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of osteoart 2004 INTRODUCTION: The objective of this study was to evaluate the potential economic implications of using etoricoxib versus non-selective NSAID alternatives in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in the UK. STUDY DESIGN: Decision-analytical modelling was used to calculate the expected costs and consequences of the use of etoricoxib compared with non-selective NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), NSAIDs plus histamine H2 receptor antagonists and NSAIDs plus misoprostol over a continuous treatment period of 1 year. METHODS: The model considered direct medical costs from the perspective of the UK National Health Service (NHS) and used data from phase IIb and III clinical trials of etoricoxib to determine probabilities of gastrointestinal (GI) events. Model outcomes were defined as resource-consuming GI-related events, including clinically evident gastroduodenal perforations, symptomatic gastroduodenal ulcers, or upper GI bleeding (collectively, PUBs ['perforation, ulcers and/or bleeding']). Resource utilisation and costs (2002 values) for the treatment of OA and RA as well as GI events were based on published literature and information available from UK-specific sources. MAIN OUTCOME MEASURES AND RESULTS: The model suggests that etoricoxib is cost saving compared with non-selective NSAIDs plus PPIs or non-selective NSAIDs plus misoprostol. The model also suggests that etoricoxib is cost effective in terms of the incremental cost per QALY gained for non-selective NSAIDs alone (pound 19,766) and for non-selective NSAIDs plus H2 antagonists (pound 9350). The incremental cost of etoricoxib per PUB avoided was pound 12,446 versus non-selective NSAIDs alone and pound 6438 versus NSAIDs co-prescribed with H2 antagonists. For patients without the presence of specific GI risk factors (history of GI event, corticosteroid use or disability), etoricoxib may be cost effective for patients over age 56 years, assuming a cost-effectiveness threshold of pound 30,000 per QALY gained. Etoricoxib may also be cost effective in patients of all ages who had at least one specific GI risk factor. CONCLUSIONS: The model suggests, with its underlying assumptions and data, that etoricoxib is a cost-effective alternative to therapeutic regimens involving non-selective NSAIDs for OA or RA, from the UK NHS perspective. Etoricoxib may be cost saving and dominant over non-selective NSAIDs used together with a PPI or misoprostol. When compared with non-selective NSAIDs alone or non-selective NSAIDs co-prescribed with H2 antagonists, the incremental cost per QALY gained with use of etoricoxib was within the generally accepted threshold for cost effectiveness (less than pound 30,000 per QALY gained).
12143976 Fracture of the greater trochanter during hip replacement: a retrospective analysis of 21/ 2002 Jun We reviewed retrospectively 373 total hip replacements operated on using a lateral approach with the patient in a supine position. We found 21 iatrogenic fractures of the greater trochanter, all in women. 15 cases were diagnosed during the operation and were treated with wire fixation. 6 fractures were diagnosed on radiographs during the first 3 months following the operation. 2 of these 6 cases presented in association with dislocation of the prosthesis; 1 after 6 weeks and 1 after 2 months. Displaced nonunion occurred in2 cases, 5 healed with minimal displacement and 14 with no displacement. 8 patients limped slightly at follow-up after mean 4 (1-7) years and 4 had some pain over the lateral thigh.
15059219 Collagenolytic (necrobiotic) granulomas: part 1--the "blue" granulomas. 2004 May A collagenolytic or necrobiotic non-infectious granuloma is one in which a granulomatous infiltrate develops around a central area of altered collagen and elastic fibers. The altered fibers lose their distinct boundaries and exhibit new staining patterns, becoming either more basophilic or eosinophilic. Within the area of altered collagen, there may be deposition of acellular substances such as mucin (blue) or fibrin (red), or there may be neutrophils with nuclear dust (blue), eosinophils (red), or flame figures (red). These color distinctions can be used as a simple algorithm for the diagnosis of collagenolytic granulomas, i.e. "blue" granulomas vs. "red" granulomas. Eight diagnoses are included within these two groupings, which are discussed in this two-part article. In this first part, the clinical presentation, pathogenesis, and histologic features of the "blue" collagenolytic granulomas are discussed. These are the lesions of granuloma annulare, Wegener's granulomatosis, and rheumatoid vasculitis. In the subsequent half of this two-part series, the "red" collagenolytic granulomas will be discussed; these are the lesions of necrobiosis lipoidica, necrobiotic xanthogranuloma, rheumatoid nodules, Churg-Strauss syndrome, and eosinophilic cellulitis (Well's syndrome).