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

ID PMID Title PublicationDate abstract
19026208 Deep infection in the sinus tarsi after triple arthrodesis in rheumatoid patients: a case 2008 Nov BACKGROUND: Triple arthrodesis can be used to correct hindfoot deformities in rheumatoid patients. Postoperative deep infections after triple arthrodesis are challenging to treat often requiring both operative debridement and antimicrobial therapy. The purpose of the present study was to review the treatment of deep infections in the sinus tarsi region in rheumatoid patients after triple arthrodesis using antimicrobial therapy and Papineau bone grafting or local muscle flap. MATERIALS AND METHODS: Seven rheumatoid patients out of 97 who underwent triple arthrodesis between January 1997 and June 2006 had a deep postoperative infection in the sinus tarsi region. These infections were treated with systemic antibiotic therapy combined with open cancellous bone grafting (Papineau technique) in four cases and with a local muscle flap (adductor digiti minimi) in three cases. RESULTS: The median time from diagnosis of the deep infection to complete healing in six patients averaged 22 weeks, while one patient developed sepsis and died one year later. The most common pathogens were staphylococcus epidermis and staphylococcus aureus; a total of 15 pathogens were found. The average number of revision operations before the infection was considered to have resolved completely was seven. CONCLUSION: The rate of deep infections was 7.2% among rheumatoid patients. Infections are challenging to treat and cause prolonged morbidity. Surgical debridement and systemic antibiotic therapy combined with Papineau grafting or a local muscle flap usually yielded successful results after postoperative deep infection of the sinus tarsi region in rheumatoid patients.
18633424 A transmembrane polymorphism in FcgammaRIIb (FCGR2B) is associated with the production of 2008 Dec The aim of the current study was to determine whether the FcgammaRIIb 187-Ile/Thr polymorphism is a predisposition factor for subtypes of RA defined by disease severity and production of autoantibodies against cyclic citrullinated peptides (anti-CCPs) in Taiwanese RA patients. Genotype distributions and allele frequencies of FcgammaRIIb 187-Ile/Thr were compared between 562 normal healthy controls and 640 RA patients as stratified by clinical parameters and autoantibodies. Significant enrichment of 187-Ile allele was observed in RA patients positive for anti-CCP antibodies as compared with the anti-CCP negative RA patients (P=0.001, OR 1.652 (95% CI 1.210-2.257)) or as compared with the normal controls (P=0.005, OR 1.348 (95% CI 1.092-1.664)). In addition, 187-Ile allele was found to be enriched in RA patients positive for rheumatoid factor (RF) compared to the RF negative RA patients (P=0.024, OR 1.562 (95% CI 1.059-2.303)). Furthermore, the homozygotes were enriched in destructive male RA patients (P=0.035; OR 2.038 (95% CI 1.046-3.973)) and the 187-Ile allele was associated with early-onset of RA in Taiwanese patients (P=0.045, OR 1.548 (95% CI 1.007-2.379)). Thus, FcgammaRIIb SNP 187-Ile/Thr may influence the RA phenotypes in Taiwanese RA.
18511715 Influence of musculoskeletal conditions on oral health among older adults. 2008 Jul Both musculoskeletal disorders and diseases of the oral cavity are common and potentially serious problems among older persons, yet little attention has been given to the links between them. Several musculoskeletal diseases, including osteoporosis, Paget's disease, and arthritic disorders, may directly involve the oral cavity and contiguous structures. Drugs used to treat musculoskeletal diseases, including corticosteroids and bisphosphonates, increase the risk of suppression of the immune system and osteonecrosis of the jaw, respectively. Many people with disabling osteoarthritis, rheumatoid arthritis, and other conditions have difficulty practicing good oral hygiene and traveling to dental offices for professional help. Various inexpensive measures can help such individuals, including education of their caregivers and provision of antimicrobial mouthwashes and special toothbrushes.
17907223 Problems faced at work due to inflammatory arthritis: new insights gained from understandi 2007 Oct 15 OBJECTIVE: A qualitative study was conducted to better understand patients' perspective on their experience at work in relation to their inflammatory arthritis (IA). Objectives were to identify the problems and barriers to employment that persons with IA face at work because of arthritis, understand why these issues are problematic, and identify strategies helpful for maintaining employment. METHODS: Five focus groups were conducted with 36 employed adults with IA (75% rheumatoid arthritis) recruited from rheumatology practices and outpatient arthritis treatment programs. Script design used brainstorming techniques to identify problems and helpful strategies, and root cause analysis to capture in-depth information about underlying causes of problems. Descriptive qualitative analysis of transcripts was performed by 2 researchers independently to identify problems and organize them into topics and broad categories. RESULTS: Problems clustered around 4 categories: arthritis symptoms, working conditions, interpersonal difficulties at work, and emotional challenges. New insights gained included identifying fatigue as the aspect of IA most limiting employment; challenges posed by invisibility, fluctuation, and unpredictability of arthritis; complexity of interpersonal relationships at work; reluctance to disclose or draw attention to arthritis; numerous barriers to using available supports and requesting job accommodations, including fear of disclosure and concern it could be perceived by coworkers as favoritism; loss of self-efficacy at work; and many emotional challenges. CONCLUSION: This research identified new issues that are meaningful to individuals working with arthritis and that deserve greater attention by professionals counseling people on employment, in intervention efforts to help maintain employment, and in arthritis employment studies.
16487688 A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid 2006 May Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.
17006705 Immunogenicity, efficacy and adverse events of adalimumab in RA patients. 2007 Jan To assess the immunogenicity of adalimumab, a human anti-TNF-alpha mAb, we evaluated the formation of antibodies to adalimumab, efficacy and adverse events among 15 patients with highly active rheumatoid arthritis. Four patients were treated with adalimumab as monotherapy, and 11 patients with concomitant DMARDs. Disease activity was measured by DAS28. The antibodies were detected by ELISA. Thirteen (87%) patients withdrew from therapy within 45 weeks and overall 13 (87%) patients showed antibodies to adalimumab including 11 patients who withdrew from therapy. In four patients without concomitant DMARDs and in nine patients with concomitant DMARDs, we detected anti-adalimumab antibodies. Overall, five of seven patients with adverse drug reactions and all nine patients with lack of efficacy were associated with the formation of antibodies. Two antibody-positive patients developed an exantheme. The results indicate that adalimumab is, in spite of its fully human sequences, immunogenic and induces antibodies in a high rate of adalimumab-treated patients.
18759293 Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with 2008 Sep OBJECTIVE: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was studied in a first-in-human trial in rheumatoid arthritis (RA) patients receiving concomitant methotrexate (MTX). METHODS: The ACTION trial was a combined phase I/II study of placebo plus MTX versus ocrelizumab plus MTX in 237 RA patients (intent-to-treat population). During phase I, 45 patients were treated with 1 of 5 escalating doses of study drug (infusions on days 1 and 15, 10-1,000 mg per each infusion). An additional 192 patients were randomized during phase II. Eligible patients had active disease, an inadequate response to treatment with at least MTX, rheumatoid factor positivity, and elevated levels of acute-phase reactants. The total study duration was 72 weeks. B cell pharmacodynamics over time was investigated. RESULTS: Baseline demographics were similar among the treatment groups. Based on the entire 72-week data set, the incidence of serious adverse events in the ocrelizumab-treated patients was 17.9%, as compared with 14.6% in placebo-treated patients. The incidence of serious infections was 2.0% in all ocrelizumab-treated patients and 4.9% in placebo-treated patients. Infusion-associated adverse events were mostly grade 1 or grade 2 and were more frequent around the time of the first infusion. No serious infusion-associated adverse events were reported in the ocrelizumab group. Evidence of clinical activity was observed at all doses evaluated. Peripheral B cell depletion after infusion was rapid at all doses, with earlier repletion of B cells at doses of 10 mg and 50 mg. Human anti-human antibodies were detected in 19% and 10%, respectively, of those receiving 10 mg and 50 mg of ocrelizumab, compared with 0-5% of those receiving 200, 500, and 1,000 mg. CONCLUSION: Ocrelizumab therapy in combination with MTX was well tolerated. Doses of 200 mg (2 infusions) and higher showed better clinical responses, better reduction of C-reactive protein levels, and very low immunogenicity.
18753157 The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exp 2009 Jul OBJECTIVE: To evaluate the safety of biological treatments for rheumatoid arthritis (RA) using results from randomised controlled trials (RCT). METHODS: The literature was searched to December 2007 for RCT evaluating inhibitors of tumour necrosis factor alpha (anti-TNF) for RA. Safety data were abstracted and risk estimates were calculated using three approaches, meta-analysis with and without adjustment for exposure and simple exposure-adjusted pooling. RESULTS: Eighteen randomised trials involving 8808 RA subjects were included. Treatment with recommended doses of anti-TNF found no increase in the odds of death (odds ratio (OR) 1.39; 95% CI 0.74 to 2.62), serious adverse events (OR 1.11; 95% CI 0.94 to 1.32), serious infection (OR 1.21; 95% CI 0.89 to 1.63), lymphoma (OR 1.26; 95% CI 0.52 to 3.06), non-melanoma skin cancers (OR 1.27; 95% CI 0.67 to 2.42) or the composite endpoint of non-cutaneous cancers plus melanomas (OR 1.31; 95% CI 0.69 to 2.48) when evaluated using the unadjusted meta-analytic method. Risk estimates were similar with the other methods. For subjects who received two to three times the recommended doses of anti-TNF the risk of serious infection was increased with the unadjusted meta-analytic and pooled analysis, (OR 2.07; 95% CI 1.31 to 3.26) and (risk ratio (RR) 1.83; 95% CI 1.18 to 2.85), respectively, but not increased in the exposure-adjusted meta-analysis (RR 1.99; 95% CI 0.90 to 4.37). Meta-regression identified that the risk of serious infection with anti-TNF therapy decreases with increasing trial duration (p = 0.035). CONCLUSION: Meta-analytic and exposure-adjusted pooled analyses on over 8800 RA subjects in RCT treated over an average of 0.8 years did not identify an increased risk of serious adverse events with recommended doses. High-dose anti-TNF therapy was associated with a twofold increase in the risk of serious infections.
16870801 Current clinical applications of omega-6 and omega-3 fatty acids. 2006 Aug BACKGROUND: Recent years have brought a resurgence of research interest in fatty acids, with studied fields running the gamut of human disease. This movement has run in parallel with an increased interest in using nutrition modalities as therapeutic measures, as opposed to their conventional role as energy sources. The aim of this manuscript is to provide a basic review of current clinical applications of omega-6 and omega-3 fatty acids, with a particular focus on the latter. METHODS: A selective review of the voluminous literature, including randomized controlled trials, meta-analyses, population studies, and case reports, was used to compile data and identify trends in pertinent clinical applications of fatty acid therapy. CONCLUSIONS: There are a myriad of disorders and maladies that seem to benefit from fatty acid supplementation, specifically omega-3 fatty acids. It has clearly been shown that omega-3 fatty acid supplementation provides a protective benefit in heart disease, and in particular sudden cardiac death. Rheumatoid arthritis (RA) is another disease entity that has been proven to benefit from this nutrition intervention, with improvement in symptoms and diminished nonsteroidal antiinflammatory drug (NSAID) usage. In addition, many psychiatric disorders, particularly schizophrenia and major depressive disorder (MDD), have shown positive results when supplementation has been used as an adjunct to standard pharmacotherapy. The remainder of clinical applications for omega-3 fatty acids requires further investigation. Specifically, according to preliminary clinical evidence, parenteral administration of fatty acids warrants further study.
18807725 [Clinical randomized study of bee-sting therapy for rheumatoid arthritis]. 2008 Jun OBJECTIVE: To observe the clinical effect of bee-sting (venom) therapy in the treatment of rheumatoid arthritis (RA). METHODS: One hundred RA patients were randomly divided into medication (control) group and bee-venom group, with 50 cases in each. Patients of control group were treated with oral administration of Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7. 5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi-points and the above-mentioned Western medicines. Ashi-points were selected according to the position of RA and used as the main acupoints, supplemented with other acupoints according to syndrome differentiation. The treatment was given once every other day and all the treatments lasted for 3 months. RESULTS: Compared with pre-treatment, scores of joint swelling degree, joint activity, pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking duration, morning stiff duration in bee-venom group and medication group were improved significantly (P<0.05, 0.01). Comparison between two groups showed that after the therapy, scores of joint swelling, pain and pressing pain, joint-swelling number and morning stiff duration, and the doses of the administered MTX and Mobic in bee-venom group were all significantly lower than those in medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was markedly higher than that in medication group (P<0.05). In addition, the relapse rate of bee-venom group was obviously lower than that of medication group (P<0.05; 12% vs 32%). CONCLUSION: Combined application of bee-venom therapy and medication is superior to simple use of medication in relieving RA, and when bee-sting therapy used, the commonly-taken doses of western medicines may be reduced, and the relapse rate gets lower.
17265486 Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthri 2007 Feb OBJECTIVE: Regulatory T cells play a suppressive role in many autoimmune diseases and can potentially affect various steps in the progression of disease. The purpose of this study was to analyze the role of Treg cells in the control of arthritis development. METHODS: Using crosses and cell transfers, we tested the effect of the scurfy loss-of-function mutation of the Foxp3 gene in the K/BxN mouse model. In this model, arthritis develops as the result of the production of high levels of pathogenic autoantibodies. RESULTS: The absence of Treg cells in K/BxN mice led to faster and more aggressive arthritis. Strikingly, disease also spread to joints not normally affected in this model. The absence of Treg cells resulted in an acceleration of the immunologic phase of disease, with significantly earlier autoantibody production. However, the broadened spectrum of affected joints in Foxp3-mutant mice was not due to the earlier appearance of autoantibodies and could not be reproduced by increasing the anti-glucose-6-phosphate isomerase antibody load, which demonstrates an impact of Treg cells on effector phase manifestations. In addition, FoxP3+,CD25+ Treg cells accumulated in inflamed joints, even in nontransgenic animals. This preferential localization mimics that in human arthritides and indicates a preferential homing/retention of Treg cells to sites of inflammation. CONCLUSION: These results indicate that Treg cells play a role in antibody-mediated arthritis at several levels. Treg cells are involved in constraining the immune phase of disease, as well as limiting the articular damage provoked by the pathogenic autoantibodies in terms of severity and of the range of affected joints, which may contribute to the limited distal predominance of many arthritides.
17477938 Tissue distribution of humanized anti-human Fas monoclonal antibody (R-125224) based on fa 2007 May 8 R-125224 is a novel humanized anti-human Fas monoclonal antibody prepared from HFE7A, which is a monoclonal mouse IgG anti-Fas antibody, by grafting the mouse complementarity-determining regions to human IgG, presently being developed as a drug for treatment of rheumatoid arthritis. In the present study, we investigated the tissue distribution of radioactivity in cynomolgus monkeys with collagen-induced arthritis at the arm joint (CIA monkeys) after intravenous administration of (125)I-labeled R-125224 ((125)I-R-125224). At 168 h after administration, we observed a high radioactivity in the bone marrow, thymus, lungs, liver, adrenals, spleen, ovaries, axillary lymph node and mesenteric lymph node compared to the radioactivity in the plasma. These tissues and organs in human are reported to express Fas antigen, strongly suggesting a specific binding of (125)I-R-125224 to Fas antigen in cynomolgus monkeys. Semi-micro autoradioluminograms of arm joint showed that radioactivity is detected in pharmacological site, such as the bone marrow and articular cavity at 168 h. The kinetics in binding of R-125224 to activated monkey lymphocytes and hepatocytes was also investigated. K(d) values of activated lymphocytes and hepatocytes were 1.51+/-0.08 and 0.60+/-0.11 nM, respectively, which were similar to those values in human lymphocytes and hepatocytes, demonstrating that R-125224 cross-reacts with the monkey Fas antigen.
19035425 Incidence and risk factors of prosthetic joint infection after total hip or knee replaceme 2008 Dec 15 OBJECTIVE: Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic joint infection and to clarify if RA is an independent predictor of this complication. METHODS: This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine whether RA is an independent risk factor for prosthetic joint infection. RESULTS: We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%) joint arthroplasties were complicated by an infection during a mean +/- SD followup of 4.3 +/- 2.4 years. Revision arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02-8.75) and a previous prosthetic joint infection of the replaced joint (HR 5.49, 95% CI 1.87-16.14) were significant predictors of postoperative prosthetic joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic joint infections (HR 4.08, 95% CI 1.35-12.33) in patients with RA. CONCLUSION: Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.
17533095 Radiography: a review for the rehabilitation professional. 2007 Apr In the normal course of practice, rehabilitation professionals are not typically provided with x-rays or radiology reports. Hand therapists who obtain x-rays or reports will glean valuable information about the patient that might otherwise go unidentified. Unique details discovered from an x-ray can contribute to improved clinical treatment plans and functional outcomes. Radiography is the general term used to describe the commonly known imaging procedures of x-ray and fluoroscopy. The purposes of this article are to provide the reader with an overview of basic radiography terminology and provide information to help better understand the typical positions and views used in upper extremity radiography. With this knowledge, guidelines for reviewing x-rays will be presented and several examples of bony pathology revealed by x-rays will be presented along with several case studies.
16508937 Deiminated Epstein-Barr virus nuclear antigen 1 is a target of anti-citrullinated protein 2006 Mar OBJECTIVE: To test the hypothesis that deimination of viral sequences containing Arg-Gly repeats could generate epitopes recognized by anti-citrullinated protein antibodies (ACPAs) that are present in rheumatoid arthritis (RA) sera. METHODS: Multiple antigen peptides derived from Epstein-Barr virus (EBV)-encoded Epstein-Barr nuclear antigen 1 (EBNA-1) were synthesized, substituting the arginines with citrulline, and were used to screen RA sera. Anti-cyclic citrullinated peptide antibodies were purified by affinity chromatography and tested on a panel of in vitro deiminated proteins. Their ability to bind in vivo deiminated proteins was evaluated by immunoprecipitation, using EBV-infected cell lines. RESULTS: Antibodies specific for a peptide corresponding to the EBNA-1(35-58) sequence containing citrulline in place of arginine (viral citrullinated peptide [VCP]) were detected in 50% of RA sera and in <5% of normal and disease control sera. In addition, affinity-purified anti-VCP antibodies from RA sera reacted with filaggrin-derived citrullinated peptides, with deiminated fibrinogen, and with deiminated recombinant EBNA-1. Moreover, anti-VCP antibodies immunoprecipitated, from the lysate of calcium ionophore-stimulated lymphoblastoid cell lines, an 80-kd band that was reactive with a monoclonal anti-EBNA-1 antibody and with anti-modified citrulline antibodies. CONCLUSION: These data indicate that ACPAs react with a viral deiminated protein and suggest that EBV infection may play a role in the induction of these RA-specific antibodies.
16906370 Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in me 2006 This report documents the results of a study performed to examine clinical use of mizoribine (MZR), using data from a large-scale prospective cohort study, IORRA (Institute of Rheumatology Rheumatoid Arthritis). The number of patients with RA entered in this study from October 2000 through October 2003 was 6238. Three hundred and six patients (4.9%) received MZR therapy. Mizoribine users who were taking methotrexate (MTX) (MTX-MZR group, n = 94) and over 70 years of age (elderly group, n = 45) were collected. Cumulative retention rates of MZR were calculated by Kaplan-Meier analysis. Median drug survival of MZR was 28 months for the poor responders to MTX and 43 months for the poor responders to MZR, with no significant difference between these groups. Cumulative retention rate of MZR in the elderly group did not show a significant difference compared to that in patients aged under 70 years. Ten patients (10.6%) in the MTX-MZR group and 10 patients (22.2%) in the elderly group experienced adverse effects of MZR. None of these adverse effects was serious. This study indicated that, although MZR has not been frequently prescribed for RA patients, it may be useful and relatively safe for patients who are poor responders to MTX as an additional regimen to MTX therapy as well as for elderly patients.
18668561 High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patie 2008 Aug OBJECTIVE: To estimate the 10-year absolute risk of cardiovascular (CV) events in newly diagnosed rheumatoid arthritis (RA) patients and the potential contribution of CV risk factors to absolute risk assessment. METHODS: A population-based incidence cohort of RA patients (defined according to the American College of Rheumatology 1987 criteria) was assembled and compared with an age- and sex-matched non-RA cohort. Data were collected on CV risk factors and CV events. Cox regression models were used to estimate the 10-year risk of a combined CV end point, adjusting for CV risk factors. Subjects were classified into 5 risk categories based on their 10-year absolute risk. RESULTS: The absolute CV risk in RA patients was similar to that in non-RA subjects who were 5-10 years older. The absolute risk varied substantially according to the presence of CV risk factors. The 10-year absolute CV risk among 60-69-year-old RA patients with no risk factors was 16.8%, but rose to 60.4% if risk factors such as smoking, hypertension, dyslipidemia, diabetes, and obesity were present. Among RA patients with a low body mass index, in addition to the above risk factors, the 10-year absolute CV risk rose to 86.2%. CONCLUSION: More than half of the newly diagnosed RA patients who were 50-59 years of age and all of those >60 years of age had a >10% risk of CV disease within 10 years of their RA incidence and should be targeted for specific CV risk reduction strategies tailored to their personal risk profiles.
17080518 An index of patient reported outcomes (PRO-Index) discriminates effectively between active 2006 Nov OBJECTIVE: To analyze 2 indices composed of the 3 patient reported outcomes (PRO) in the American College of Rheumatology (ACR) Core Data Set--physical function, pain, and global estimate--without joint count or laboratory data, for capacities to distinguish active from control treatments in 4 pivotal clinical trials. METHODS: Data from 4 clinical trials involving adalimumab, in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARD) or as monotherapy, versus control treatment were made available to analyze properties of various indices. A categorical PRO-Index M was defined as "majority" improvement in 2 of the 3 PRO measures at 20%, 50%, and 70% levels; results were evaluated to analyze agreement with ACR20, ACR50, ACR70 responses and an "all Core Data Set measures" index based on 4 of the 7 measures having such levels of improvement. A continuous PRO-Index C was defined as the median or 2nd highest of 3 percentage differences from baseline to endpoint; results were evaluated to analyze agreement with a continuous ACR-N, "all Core Data Set measures" index, and Disease Activity Score 28 (DAS28). RESULTS: All indices distinguished active versus control treatment at similar levels, including PRO-Index M versus ACR20, ACR50, and ACR70 responses, and PRO-Index C versus DAS28. CONCLUSION: PRO indices based only on patient questionnaire data, without joint counts or laboratory tests, may be useful quantitative measures of therapeutic efficacy for use in standard rheumatology clinical care.
18302252 Gene expression analysis of major lineage-defining factors in human bone marrow cells: eff 2008 Jul Adult bone marrow cells (BMCs) include two populations:;mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and age-related disorders on lineage differentiation, we performed quantitative RT-PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar-gamma for adipocytes, sox9 for chondrocytes, and rankl for osteoclasts, in bone marrow from 80 healthy subjects and patients (14-79 years old) with two age-related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis-related genes, bcl-2 and drak1, were studied. RANKL and PPAR-Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age-related decline in CBFa1 transcripts. DRAK1 expression showed an age-associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females (p < 0.01). Compared with age-matched controls, RA patients exhibited increased RANKL, PPAR-Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPAR-Gamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age-related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age-related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss.
18424211 Organizing pneumonia after rituximab therapy: Two cases. 2008 May Rituximab, a chimeric monoclonal antibody against CD20, very rarely causes lung toxicity. Clinical presentations include lung infiltrates, alveolar hemorrhage, and adult respiratory distress syndrome. Three cases of organizing pneumoinia (formerly called bronchiolitis obliterans with organizing pneumonia or BOOP) have been reported. In our experience, organizing pneumonia occurred in 2 of 25 patients treated with rituximab, for RA and Castleman's disease, respectively. Because organizing pneumonia may be asymptomatic, as illustrated by one of our cases, we recommend obtaining a chest radiograph routinely before rituximab re-treatment.