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ID PMID Title PublicationDate abstract
17336914 Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of 2007 May PURPOSE: To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG). DESIGN: Retrospective cross-sectional study. METHODS: Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the other rings (e.g., R(1)/R(2), R(1)/R(3)) were compared with limits derived from control eyes. RESULTS: The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R(1)/R(2) ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment. CONCLUSIONS: Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed.
18338203 Reduction of urinary levels of pyridinoline and deoxypyridinoline and serum levels of solu 2008 Sep The effects of soluble TNF-alpha receptor, etanercept, on bone metabolism were investigated in patients with rheumatoid arthritis (RA). Thirty RA patients were administered etanercept once or twice a week for more than 6 months. We evaluated clinical and laboratory parameters and measured urinary excretion levels of pyridinoline (PYD), deoxypyridinoline (DPD), cross-linked N-telopeptides of type I collagen (NTX), and serum levels of bone alkaline phosphatase (BAP), osteoprotegerin (OPG), and soluble receptor activator of NFkappaB ligand (sRANKL) at the baseline and at 3 and 6 months after initial treatment with etanercept. Etanercept treatment resulted in an improvement of symptoms due to RA and in a reduction of urinary excretion levels of PYD and DPD as well as serum sRANKL levels, with a significant difference at 6 months, and an increase of serum BAP levels at 3 and 6 months after the initial treatment with etanercept. Urinary NTX and serum OPG levels did not show a significant change at 3 and 6 months after the initial treatment, but serum OPG levels did show a reverse correlation with serum CRP levels, suggesting that the regulation of inflammation in RA may result in an induction of OPG production. Etanercept may have the ability to reduce the levels of bone resorption markers and to increase the levels of a bone formation marker while reducing sRANKL formation in RA patients.
17462899 Joint stiffness of the ankle during walking after successful mobile-bearing total ankle re 2008 Jan INTRODUCTION: It has been shown that walking kinematics remain near to normal after mobile bearing total ankle replacement (TAR). However, no information is available on mechanical joint loading. The purpose of this study was to determine whether mechanical load and 'quasi-stiffness' of the ankle joint after TAR differs from the normal load and stiffness of a healthy ankle joint during walking. METHODS: Ten TAR patients and 10 age-matched healthy control subjects (CO) participated in this study. Participants walked barefooted on an indoor track at self-selected walking speed. 3D ankle kinematics and ground reaction force were measured and used for the calculation of 3D net joint moments, joint quasi-stiffness coefficients and internal net joint ankle work. RESULTS: Between patients and control subjects no differences were observed in peak moments and stiffness coefficient at the ankle. Internal work at the ankle during the step differed however, significantly (-0.078 (0.088) J kg(-1) versus 0.005 (0.048) J kg(-1) for TAR versus CO, p=0.02), although it could be argued that this difference was due to a minor difference in walking speed between both groups (1.02 (0.07) versus 1.09 (0.07) for TAR versus CO, p=0.02). CONCLUSION: Despite the small difference in internal work at the ankle, there was no significant difference in mechanical loading of the ankle after TAR compared to normal.
18089561 A catalytically independent physiological function for human acute phase protein group IIA 2008 Feb 22 Human group IIA phospholipase A2 (IIA PLA2) is an acute phase protein first identified at high concentrations in synovial fluid from patients with rheumatoid arthritis. Its physiological role has since been debated; the enzyme has a very high affinity for anionic phospholipid interfaces but expresses almost zero activity with zwitterionic phospholipid substrates, because of a lack of interfacial binding. We have prepared the cysteine-containing mutant (S74C) to allow the covalent attachment of fluorescent reporter groups. We show that fluorescently labeled IIA was taken up by phorbol 12-myristate 13-acetate-activated THP-1 cells in an energy-dependent process involving cell surface heparan sulfate proteoglycans. Uptake concurrently involved significant cell swelling, characteristic of macropinocytosis and the fluorescent enzyme localized to the nucleus. The endocytic process did not necessitate enzyme catalysis, ruling out membrane phospholipid hydrolysis as an essential requirement. The enzyme produced supramolecular aggregates with anionic phospholipid vesicles as a result of bridging between particles, a property that is unique to this globally cationic IIA PLA2. Uptake of such aggregates labeled with fluorescent anionic phospholipid was dramatically enhanced by the IIA protein, and uptake involved binding to heparan sulfate proteoglycans on activated THP-1 cells. A physiological role for this protein is proposed that involves the removal of anionic extracellular cell debris, including anionic microparticles generated as a result of trauma, infection, and the inflammatory response, and under such conditions serum levels of IIA PLA2 can increase approximately 1000-fold. A similar pathway may be significant in the uptake into cells of anionic vector DNA involving cationic lipid transfection protocols.
17957709 Hospitalization rates of generic metoprolol compared with the original beta-blocker in an 2007 Dec PURPOSE: A less favourable galenic profile of generic formulations of the beta-blocker metoprolol raised the concern of a higher risk for serious cardiovascular (CV) events. We assessed hospital admission rates for CV diseases and prescription prevalences of various drugs using claims data of statutory health insurances (SHIs) to compare the incidence of serious CV events among users of original and generic metoprolol. Index events included hospitalization due to myocardial infarction, hypertensive crisis and stroke. METHODS: Data files of three SHIs were linked with dispensing data of drug prescriptions from each pharmacy's electronic data processing centre on an individual basis. Incidences of hospital admissions among patients receiving original metoprolol and among patients treated with the generic equivalent were compared by logistic regression, stratified for Bremen and the rest of Northern Germany. Risk estimates and confidence intervals were adjusted for confounders. RESULTS: A total of 49,673 patients receiving metoprolol were identified within a cohort of 3,649,285 insurance members. While the crude analysis revealed a higher risk for index events in patients receiving the generic drug (Bremen: RR 1.45; Northern Germany: RR 1.14), no elevated risk remained after confounder adjustment (Bremen: OR 1.06; Northern Germany: OR 1.04). Among co-morbid conditions considered as confounders, a previous CV event and an elevated thromboembolic risk exerted the strongest effect on index events. CONCLUSIONS: SHI data are a valuable source for pharmacoepidemiology and health services research in Germany. Incidence rates of serious CV events did not reveal any noticeable differences between the original and the generic group after confounder adjustment.
19036923 Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid ar 2008 Dec 9 The ultimate goal for the treatment of autoimmunity is to restore immunological tolerance. Regulatory T cells (Treg) play a central role in immune tolerance, and Treg functional abnormalities have been identified in different autoimmune diseases, including rheumatoid arthritis (RA). We have previously shown that natural Treg from RA patients are competent at suppressing responder T cell proliferation but not cytokine production. Here, we explore the hypothesis that this Treg defect in RA is linked with abnormalities in the expression and function of CTLA-4. We demonstrate that CTLA-4 expression on Treg from RA patients was significantly reduced compared with healthy Treg and is associated with an increased rate of CTLA-4 internalization. Regulation of T cell receptor signaling by CTLA-4 was impaired in RA Treg and associated with delayed recruitment of CTLA-4 to the immunological synapse. Artificial induction of CTLA-4 expression on RA Treg restored their suppressive capacity. Furthermore, CTLA-4 blockade impaired healthy Treg suppression of T cell IFN-gamma production, but not proliferation, thereby recapitulating the unique Treg defect in RA. Our results suggest that defects in CTLA-4 could contribute to abnormal Treg function in RA and may represent a target for therapy for inducing long-lasting remission.
18979608 Tuberculous peritonitis after treatment with adalimumab. 2008 We present a case of tuberculous peritonitis in a woman with rheumatoid arthritis (RA), treated with adalimumab, and we review the association between anti-tumour necrosis factor (anti-TNF) therapy and tuberculosis. There have been only 2 case reports of peritoneal tuberculosis associated with anti-TNF and only 1 with adalimumab.
17617338 Are critical pathways and implant standardization programs effective in reducing costs in 2007 Jul BACKGROUND: Total knee replacement (TKR) operation is one of the most effective procedures, both clinically and in terms of cost. Because of increased volume and cost for this procedure during the past 3 decades, TKRs are often targeted for cost reduction. The purpose of this study was to evaluate the efficacy of two cost reducing methodologies, establishment of critical clinical pathways, and standardization of implant costs. STUDY DESIGN: Ninety patients (90 knees) were randomly selected from a population undergoing primary TKR during a 2-year period at a tertiary teaching hospital. Patients were assigned to three groups that corresponded to different strategies implemented during the evolution of the joint-replacement program. Medical records were reviewed for type of anesthesia, operative time, length of stay, and any perioperative complications. Financial information for each patient was compared among the three groups. RESULTS: Data analysis demonstrated that the institution of a critical pathway significantly shortened length of hospital stay and was effective in reducing the hospital costs by 18% (p < 0.05). In addition, standardization of surgical techniques under the care of a single surgeon substantially reduced the operative time. Selection of implants from a single vendor did not have any substantial effect in additionally reducing the costs. CONCLUSIONS: Standardized postoperative management protocols and critical clinical pathways can reduce costs and operative time. Future efforts must focus on lowering the costs of the prostheses, particularly with competitive bidding or capitation of prostheses costs. Although a single-vendor approach was not effective in this study, it is possible that a cost reduction could have been realized if more TKRs were performed, because the pricing contract was based on projected volume of TKRs to be done by the hospital.
17143555 MAP kinase subtypes and Akt regulate diosgenin-induced apoptosis of rheumatoid synovial ce 2007 Jan In the present study, we investigated the signalling pathways involved in diosgenin-induced apoptosis in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) in vitro with particular interest on Akt and MAPKs activation in relation to arachidonic acid metabolism via COX-2 pathway. MAPK activation was measured by ELISA quantification in diosgenin-treated human RA FLS. Expression of Akt and phospho-Akt was analyzed by Western blot analysis. Nuclear factor-kappaB (NF-kappaB) translocation was evaluated by electromobility shift assay. The prostanoid production (COX-2 activity) was measured by quantitative ELISA. Diosgenin-induced apoptosis in the presence of MAPK or Akt inhibitors was detected by a quantitative determination of DNA fragmentation. Treatment of human RA FLS with 40 microM diosgenin caused an activation of p38 and JNK and an inhibition of ERK phosphorylation. Akt and NF-kappaB are potentially required for diosgenin-induced apoptosis in human RA FLS because 40 microM diosgenin abrogated Akt phosphorylation which correlated with an inhibition of NF-kappaB nuclear translocation. SB203580 and SP600125 (p38 and JNK inhibitors) reduced diosgenin-induced DNA fragmentation whereas U0126 and LY294002 (MEK and PI3 kinase/Akt inhibitors) caused an amplification of proapoptotic effect of diosgenin. Diosgenin increased COX-2 activity resulting in PGE2 and 6-keto-PGF1alpha overproduction in human RA FLS. All MAPK inhibitors markedly reduced diosgenin-induced PGE2 and 6-keto-PGF1alpha synthesis except for SP600125 on 6-keto-PGF1alpha production. These results provide, for the first time, strong evidence that a combined association implicating a MEK inhibitor (U0126) and diosgenin is the most effective in inducing very strong apoptosis with down-regulation of COX-2 expression and activity in human RA FLS.
17299840 Infliximab does not suppress the tuberculin skin test (purified protein derivative). 2007 Mar OBJECTIVE: Tuberculin skin testing with purified protein derivative (PPD) is part of tuberculosis (TB) screening in patients receiving infliximab. We assessed whether infliximab, a strong inhibitor of inflammation, suppressed dermal induration, the outcome of this test. We also reassessed the booster phenomenon and the interobserver variability in tuberculin testing. METHODS: Forty-seven patients with various diagnoses, who had had a PPD test before infliximab use, were retested after infliximab treatment. The test was also assessed cross-sectionally among 31 patients with rheumatoid arthritis (RA) after 8.6 [+/- 4.1 standard deviation (SD)] months of infliximab use and in 82 patients with RA who had never used this agent. Booster phenomenon and the interobserver variability of reading the test were reassessed among 163 infliximab-naive patients with RA and Behcet's disease (BD) and 47 healthy controls. RESULTS: Among the 47 patients who received infliximab, and for whom sequential data were available, the mean skin induration was 5.9 +/- 8.0 SD mm before and 6.1 +/- 7.5 mm after 4.8 +/- 3.7 months of treatment (p = 0.890). In the cross-sectional study the mean PPD induration was 7.8 +/- 8.4 mm among infliximab-naive patients with RA, while it was 6.6 +/- 2.1 mm in those receiving infliximab (p = 0.271). Booster phenomenon was observed in 14/49 (29%) of patients with RA, 7/31 (23%) of those with BD, and 1/10 of healthy controls. Interobserver variability of PPD reading was good (kappa = 0.92). CONCLUSION: Infliximab use does not suppress the skin reaction to tuberculin. We confirm the booster phenomenon and that the PPD skin test has an acceptable interobserver reliability for an in vivo test.
17474177 [Diagnostic difficulties in polymyositis]. 2006 Polymyositis is a connective tissue disease. Although myositis is the dominant clinical manifestation, internal organs may also be affected. Arthritis occurs in 30% of patients, especially in the course of the anti-synthetase syndrome. We report on a case of a woman with polymyositis and interstitial lung disease. Arthritis and the presence of anti-cyclic citrullinated peptide antibodies in the patient's serum may suggest the diagnosis of the overlap syndrome.
16900373 Defensins- and cathepsin G-ANCA in systemic lupus erythematosus. 2006 Dec In this study, we examined the content of antineutrophil cytoplasmic antibodies (ANCA) against defensins and cathepsin G in sera from systemic lupus erythematosus (SLE) patients and their significance in estimating the activity of SLE. Defensins- and cathepsin G-ANCA in sera from 28 patients with SLE, eight patients with rheumatoid arthritis (RA) and eight patients with microscopic polyangitis (mPA) were measured by ELISA. Significantly increased defensins- and cathepsin G-ANCA were found in sera of patients with SLE and mPA when compared with the value of normal controls. Though significantly higher defensins- and cathepsin G-ANCA were detected in both active and inactive SLE patients, the value in active SLE patients was significantly higher than inactive SLE patients. After the therapy with high dose of prednisolone, the serum level of defensins- and cathepsin G-ANCA was decreased, and this decrease was sustained for at least 16 weeks. This study suggests that defensins- and cathepsin G-ANCA may serve as useful markers of the disease activity of SLE.
16900293 A tale of two citrullines--structural and functional aspects of myelin basic protein deimi 2007 Feb Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is responsible for adhesion of these surfaces in the multilayered myelin sheath. The pattern of extensive post-translational modifications of MBP is dynamic during normal central nervous system (CNS) development and during myelin degeneration in multiple sclerosis (MS), affecting its interactions with the myelin membranes and with other molecules. In particular, the degree of deimination (or citrullination) of MBP is correlated with the severity of MS, and may represent a primary defect that precedes neurodegeneration due to autoimmune attack. That the degree of MBP deimination is also high in early CNS development indicates that this modification plays major physiological roles in myelin assembly. In this review, we describe the structural and functional consequences of MBP deimination in healthy and diseased myelin.
17139865 [Shoulder pain: imaging examinations]. 2006 Sep 30 Non-traumatic shoulder pain is a diagnostic challenge for clinicians. Usually, the clinical examination is supplemented by nowadays well-defined imaging studies. Radiography is the first examination to be requested on a systematic basis. It always includes several views to study the whole scapular region (glenohumeral joint, subacromial space, acromioclavicular joint etc.). If the radiographic examination is not precise enough, a noninvasive and non-irradiating examination is performed, either ultrasonography or magnetic resonance imaging. The latter seems to be more comprehensive than ultrasonography. However, the usefulness of the association radiography-ultrasonography should be emphasized: both examinations are perfectly complementary, inexpensive and easy to access. Invasive examinations, such as CT arthrography, are still too often requested following a radiological examination. Since they do not investigate the whole shoulder, they should be limited to the investigation of specific diseases, often as part of presurgical assessments required for or by the orthopedic surgeon.
17507872 [The role of fucosylation of glycoconjugates in health and disease]. 2007 Fucose is a deoxyhexose that is present in the L-configuration of many N- and O-linked oligosaccharide structures of membrane as well as soluble glycoproteins and glycolipids produced by mammalian cells. The fucose molecule is present in ABH blood group antigens and in some oligosaccharide structures belonging to the Lewis(x), Lewis(y), Lewis(a), and Lewis(b) antigens. Characteristic of fucose is its almost exclusive presence at a terminal position, i.e. not inserted in an oligosaccharide chain. Fucose can be alpha 1,2, alpha 1,3, alpha 1,4, and alpha 1,6 linked to the glycans of glycoconjugates. This predisposes fucose to play a crucial role in biological recognition events, such as cell-cell and cell-matrix interactions. In the present review the influence of fucose on the properties and biological functions of glycoproteins is described. The state of current knowledge on the role of fucosylglycotopes, fucose-containing glycans, in many physiological processes, such as fertilization, embryogenesis, fetal development, neuron transmission, leukocytes adhesion, signal transduction, and apoptosis, as well as in diseases, such as rheumatoid arthritis, cystic fibrosis, peptic ulcer disease, inflammatory process, and cancer, is summarized. Finally, some examples of changes in fucose expression and its possible determination as a marker for diseases diagnosis and monitoring are shown.
18025126 Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rhe 2007 Nov 26 This report shows that interleukin (IL) 17-producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor beta and IL-6 additionally need IL-1 and neutralization of interferon (IFN) gamma and IL-4 for CCR6 expression. Forced expression of RORgamma t, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1beta, IL-17, or tumor necrosis factor alpha, and is suppressed by IFN-gamma or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.
17628840 [Phlegmonous gastritis in a 44-year-old woman on immunosuppressive therapy]. 2007 Jul 30 HISTORY AND ADMISSION FINDINGS: A 44-year-old woman was on long-term immunosuppressive therapy with leflunomide and adalimumab for rheumatoid arthritis. She was admitted to the emergency room with diffuse abdominal pain of sudden onset. On physical examination she had rebound tenderness in all four abdominal quadrants. INVESTIGATIONS: The white blood cell count was 3300/l, C-reactive protein 25 mg/dl and serum lactate 10 mmol/l. Abdominal computed tomography revealed a diffusely thickened gastric wall and ascites. At explorative laparotomy 1000 ml of a cloudy peritoneal fluid were aspirated and found to be negative for bacteria. But a culture of a mesenterial smear grew streptococci group A. Intra-operative endoscopy showed extensive hemorrhagic gastritis. Because there was no perforation or transmural necrosis gastric resection was not performed. DIAGNOSIS, TREATMENT AND COURSE: Diffuse thickening of the gastric wall, extended mucosal necrosis and the peritoneal finding of streptococci in an immunocompromised patient suggested the diagnosis of phlegmonous gastritis. On treatment with antibiotics and proton pump inhibitor the patient made a slow recovery over the following eight weeks. Nine months after the event an asymptomatic antral stricture was noticed at follow-up gastroscopy. CONCLUSION: Phlegmonous gastritis is a rare but life-threatening complication in immunosuppressed patients.
17257224 CD25-expressing B-lymphocytes in rheumatic diseases. 2007 Feb B cells play an important role in the development of autoimmune diseases due to their production of autoantibodies, antigen-presenting capacity and production of pro-inflammatory cytokines. The purpose of the present study was to analyse B cells from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, with respect to their expression of the IL-2 receptor (IL-2R) subunit CD25. Using flow cytometry, we found that CD25(+) B cells from RA patients expressed significantly higher frequencies of CD122 and CD132 than CD25(+) B cells from control subjects, indicating a fully functional IL-2R. These CD25(+) B cells also expressed higher frequencies of the co-stimulatory molecule CD80, whereas IgM and IgA expression was decreased compared with CD25(+) B cells from healthy controls. In addition B cells from SLE patients co-expressed CD25 together with CD80, CD122, and CD132, but to a lower degree IgD and IgM, when compared with healthy controls. Taken together, our results indicate that CD25(+) B cells from RA and SLE patients are in a highly activated state, display a more mature phenotype and suggest that this B cell subset may be involved in the pathogenesis of RA and SLE.
17668369 Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AID 2007 Aug Pfizer Inc is developing maraviroc, a CCR5 receptor antagonist for the treatment of HIV-1 infection and rheumatoid arthritis. In April 2007, the FDA advisory committee voted to approve maraviroc for HIV-1 infection. Phase II and III clinical trials, and post-approval studies are ongoing in both treatment-experienced and -naive HIV patients. Phase II trials have also been initiated in patients with rheumatoid arthritis.
18215798 Retinal toxicity secondary to Plaquenil therapy. 2008 Feb BACKGROUND: Hydroxychloroquine sulfate (Plaquenil; Sanofi-Aventis, Bridgewater, New Jersey) is an antimalarial agent, which is sometimes used for the treatment of certain autoimmune disorders. Its use has been associated with ocular side effects; the most concerning is toxic maculopathy. CASE REPORT: A 71-year-old arthritic white woman requested a second opinion regarding retinal Plaquenil toxicity. The patients history was significant for seronegative rheumatoid arthritis diagnosed 6 years prior. She had taken Plaquenil 400 mg a day for about 5 years but had discontinued the drug 6 months before when bilateral central scotomas were first noted. At the consultation visit, her visual acuities were 20/20 in both eyes. SITA-Standard 10-2 disclosed a dense scotoma with 4 degrees of central sparing in each eye. Fundus examination found retinal pigment epithelium changes bilaterally; no "bulls eye" retinopathy was observed. CONCLUSION: Withdrawal of the medication is the only effective treatment for Plaquenil toxicity and, even then, the toxic effects may progress because of the slow clearance of the drug. Though controversy exists regarding screening recommendations, a baseline ophthalmic examination should be performed on all patients before initiating Plaquenil. If a patient is considered low risk, examinations can be scheduled annually. For high-risk patients, 6-month progress visits are strongly recommended.