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

ID PMID Title PublicationDate abstract
19360410 DNase1 exon2 analysis in Tunisian patients with rheumatoid arthritis, systemic lupus eryth 2009 Nov Autoimmune diseases (AID) are caused by the loss of immunological tolerance against self-antigens. The deoxyribonuclease I (DNASE1) gene seems to participate in the genetic susceptibility of some AID. In fact, two mutations were reported among systemic lupus erythematosus (SLE) patients from Japan and Spain (the 172 A → T mutation (K5X) and the 46_72 deletion, respectively). The aim of our work was to evaluate the DNASE1 contribution in the genetic susceptibility of rheumatoid arthritis (RA, n = 151), Sjögren syndrome (SS, n = 55) and SLE (n = 34) in Tunisia. DNA from patients and healthy subjects (n = 232) were explored. Both reported mutations were absent among patient and control subjects. The DNASE1 exon2 sequence was analysed among 26 control subjects to identify new polymorphic variations that are possible. Five known SNPs were explored. The G/T transversion (rs8176927: R2S) was the most polymorphic functional nonsynonymous SNP. Using PCR-RFLP method, all DNAs were genotyped for rs8176927 for a case-control design. The statistical analysis showed no significant differences between patients and controls genotype data. In conclusion, our study showed, on the one hand, the absence of the K5X mutation and the 46_72 deletion in Tunisian patients affected with RA, SS and SLE and healthy subjects, and, on the other hand, the absence of association between the R2S polymorphism and the genetic susceptibility of RA, SS and SLE.
20448285 Comparison of utility measures and their relationship with other health status measures in 2010 Oct OBJECTIVES: The aim of this study was to compare three health utility instruments (15D, EQ-5D, SF-6D) and a rating scale for health (EQ-Visual Analogue Scale (VAS)) and to investigate their relationship to clinical parameters in patients with rheumatoid arthritis (RA). METHODS: Data were collected from 1041 patients with RA. Agreement between the instruments was assessed with Bland-Altman plots. Linear regression models were fitted for the different instruments and Health Assessment Questionnaire (HAQ) scores, age, gender, patient global, disease duration and educational level. Differences in utility scores across levels of global health and disability, were investigated as well as correlations with disease-specific health status measures. RESULTS: The score range in the 1041 patients with RA was 0.41-1.0 for 15D, -0.48 to 1.0 for EQ-5D, 0.0-1.0 for EQ-VAS and 0.30-1.0 for SF-6D, with a bimodal distribution for EQ-5D. Bland-Altman plots indicated poor agreement between EQ-5D and SF-6D/15D and moderate agreement between SF-6D and 15D. Utility scores were correlated with disease-specific measures, pain and fatigue (r>0.60). Mean utilities ranged from 0.30 (EQ-5D) to 0.69 (15D) in patients rating their own health as poor. When correcting for a non-linear relationship between HAQ and EQ-5D/SF-6D in linear regression models, the estimated utilities had non-overlying CI for HAQ values >1.4. CONCLUSIONS: Diverging scores were observed across utility instruments, especially in patients with high HAQ scores. The choice of utility instrument may have an impact on the results of cost-utility analyses, with large hypothetical differences in price per quality-adjusted life year.
21433310 [Association between BsmI vitamin D receptor gene polymorphism and serum concentration of 2010 INTRODUCTION: Vitamin D is an important modulator of the autoimmune process exerting its effects through the nuclear vitamin D receptor (VDR) with transcription factor properties. Mutations in the VDR gene may be important for vitamin D action on immunocompetent cells. Studies on the influence of serum levels of vitamin D and of vitamin D supplementation on rheumatoid arthritis (RA) activity, progression, and prognosis are sparse, limited to a few parameters, and often conflicting. The aim of this study was (a) to assess the relationship between the presence of BsmI VDR gene polymorphism and RA susceptibility, activity, and progression; (b) to compare vitamin D serum concentration in RA patients and in the control group; (c) to correlate vitamin D concentration in serum, vitamin D substitution in patients, demographic data, disease duration, RA functional and radiologic grade, RA activity, and presence of some antibodies. MATERIAL AND METHODS: The study was performed in 102 RA patients treated at the Department of Rheumatology and Internal Diseases, Pomeranian Medical University in Szczecin (PAM), and at the Rheumatology Outpatient Clinic of the First Public Clinical Hospital. The control group consisted of 57 volunteers with no connective tissue disease. 100 persons formed a control group for genetic tests. The study protocol was approved by the Bioethics Committee of the PAM. RESULTS: Low concentrations of vitamin D were found in RA patients and in the control group. Significantly lower serum concentrations of vitamin D were found in elderly patients. Elevated serum levels of 25(OH)D were associated with high functional status radiologic grades and with high RF levels. No significant correlation was found between BsmI VDR gene polymorphism and RA susceptibility or activity. BsmI polymorphism correlated only with RA functional status. CONCLUSIONS: Vitamin D serum concentration and BsmI VDR gene polymorphism may show some correlation with RA activity and progression.
20496428 Converting modified health assessment questionnaire (HAQ), multidimensional HAQ, and HAQII 2010 Oct OBJECTIVE: The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ. METHODS: Analysis was limited to the comparison of rheumatoid arthritis (RA) patients at a random observation when the HAQ was recorded in conjunction with the MHAQ (n = 29,596), the MDHAQ (n = 13,665), or the HAQII (n = 15,823). Development models were randomly limited to 80% of the data (development sample) and the remaining 20% was used for model validation. RESULTS: Two conversion formulas were developed for each of the MHAQ, the MDHAQ, and the HAQII: a short model and a long model inclusive of questions common to both the modified measures and the original HAQ. Short models explained 81-83%, and long models 82-86%, of the variance. Predicted HAQ values of zero were assigned to all cases with an MDHAQ or HAQII score of zero, with remaining cases used for model estimation. Bland-Altman plots demonstrated good concordance between actual and predicted values for each measure. The validation sample closely approximated the results from the development sample (0.005 ≤ ΔR² ≤ 0.009) for each measure. CONCLUSION: We have developed and validated highly accurate conversion formulas from the MHAQ, MDHAQ, and HAQII to the original HAQ in a large sample of RA patients. The developed models are useful for conversion of measures in the research setting. Because of substantial variability at the individual patient level, application of the formulas to individual patients is inadvisable.
19482623 Chemokines and angiogenesis in rheumatoid arthritis. 2009 Jun 1 In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine receptors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention.
20140823 TRU-015, a fusion protein derived from an anti-CD20 antibody, for the treatment of rheumat 2010 Feb TRU-015, being developed by Trubion Pharmaceuticals Inc and Pfizer Inc, is an intravenously administered anti-CD20 IgG fusion protein for the treatment of rheumatoid arthritis. TRU-015 depletes B-cells from the peripheral blood in vitro, and can mediate complement-and antibody-dependent cellular cytotoxicity. TRU-015 was well tolerated in patients with rheumatoid arthritis in phase I and II clinical trials, and demonstrated an efficacy profile similar to other biological agents approved for rheumatoid arthritis. At the time of publication, phase II trials were ongoing in patients with rheumatoid arthritis. TRU-015 could represent a novel therapy for the treatment of rheumatoid arthritis, although the efficacy, safety profile and advantages of this compound compared with existing therapeutic options would need to be established in phase III trials. In addition, this agent also may be useful to the treatment of B-cell neoplasms and autoimmune diseases.
19838716 [Methotrexate in rheumatology]. 2009 Nov Methotrexate (MTX) is a folate inhibitor which has gained a major role in the treatment of rheumatoid arthritis (RA). MTX is not only the disease modifying anti-rheumatic drug of first choice, a large number of clinical trials moreover show that biologic drugs should be combined with MTX in order to obtain optimal therapeutic efficacy. Therefore, MTX is an anchor drug for the treatment of RA. Large studies show the general safety of the drug for long term treatment. The mechanisms of action of MTX in inflammation are complex but increasingly better understood. Current publications show that first steps have been done towards prediction of therapeutic response and toxicity of MTX by analysis of gene polymorphism. Conjugates of MTX which use endogenous albumin as a drug carrier to synovitis as well as new receptor-specific folate inhibitors are currently tested in pre-clinic investigations. The goal to further develop the most successful principle of folate inhibition for the treatment of rheumatic diseases seems to be feasible.
20398019 An endocrinologist's view on relative adrenocortical insufficiency in rheumatoid arthritis 2010 Apr The concept of relative adrenal insufficiency (RAI) has been originally introduced to describe a situation in which critically ill patients, without any prior risk or evidence for adrenal insufficiency, have total serum cortisol levels inadequate for the severity of patients' illness. The concept provided a framework for other disease states, in which higher than normal adrenal function could be expected, such as in chronic inflammation. An intense research in RAI field highlighted some new methodological aspects that significantly improved assessment of adrenal function in chronic illness. Measurement of salivary cortisol may provide additional information on locally available cortisol in target tissues. Low levels of dehydroepiandrosterone (DHEAS) for given age and gender were confirmed as a simple and reliable indicator of decreased adrenal function, even in subjects with normal baseline cortisol or normal corticotropin-stimulated cortisol response. Combined lower DHEAS and lower baseline cortisol levels could be an example of hypocompetence of adrenocortical function, yet clinically not apparent.
18930988 Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus me 2009 Jul OBJECTIVES: To compare the clinical and radiological efficacy of initial vs delayed treatment with methotrexate (MTX) and infliximab (IFX) in patients with recent onset rheumatoid arthritis (RA). METHODS: In a post hoc analysis of the BeSt study (for Behandel Stratagieen, Dutch for treatment strategies), 117 patients who started initial MTX+IFX were compared with 67 patients who started MTX+IFX treatment after failing (disease activity score (DAS)>2.4; median delay to IFX: 13 months) on > or =3 traditional DMARDs. If the DAS remained >2.4, the protocol dictated IFX dose increases to 6, 7.5 and 10 mg/kg. In case of a DAS < or =2.4 for > or =6 months, IFX was tapered and finally stopped. We aimed to correct for allocation bias using propensity scores. Functional ability was measured by the Health Assessment Questionnaire (HAQ), radiological progression by Sharp/van der Heijde scoring (SHS). RESULTS: Baseline differences between the initial and delayed groups were no longer significant after propensity score adjustment. At 3 years after baseline, patients treated with initial MTX+IFX experienced more improvement in HAQ over time and were less likely to have SHS progression than patients treated with delayed MTX+IFX (p = 0.034). At 2 years after IFX initiation, more patients in the initial group compared with the delayed group could discontinue IFX after a good response (56% vs 29%, p = 0.008). CONCLUSIONS: The results of this post hoc analysis suggest that using MTX+IFX as initial treatment for patients with recent onset RA is more effective than reserving MTX+IFX for patients who failed on traditional DMARDs, with more HAQ improvement over time, more IFX discontinuation and less progression of joint damage.
21073366 An analysis of the diaminopyrimidine patent estates describing spleen tyrosine kinase inhi 2010 Dec IMPORTANCE OF THE FIELD: Discovery of small molecule inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of the leading small molecular targets with regard to clinical developments due to the efforts of Rigel and Portola. AREAS COVERED IN THIS REVIEW: Diaminopyrimidines are one of the most prominent structural elements incorporated into the design of kinase inhibitors. This review provides an extensive overview of the patent estates for the leading discovery programs at Portola and Rigel on diaminopyrimidines and how their patent estates are in relationship with the competition and prior art. WHAT THE READER WILL GAIN: An overview of the patent landscape for diaminopyrimidines. In addition, the reader will be updated on what modifications in these scaffolds lead to very potent SYK inhibitors as judged by the applications. Finally, the authors will provide their best guess on what the structure is of Portola's recently announced clinical candidate. TAKE HOME MESSAGE: The Rigel and the Portola research organizations have filed a series of patent applications on diaminopyrimidines as inhibitors of SYK. The scope of these applications is broad in a crowded chemical space. These applications contain very broad claims and the future will tell how much of the generic space claimed will be allowed in granted patents.
19410985 Prediction of wrist prognosis in patients with early rheumatoid arthritis according to rad 2009 May PURPOSE: We conducted a prospective study of patients with recent-onset rheumatoid arthritis to determine the importance of carpal height ratio (CHR) or ulnar translation ratio (UTR) in predicting radiographic progression of rheumatoid arthritis in the wrist, especially with regard to stable or progressive wrist arthritis. METHODS: We evaluated 106 wrists with early rheumatoid arthritis. Radiologic misalignment was assessed by measuring CHR and UTR. The modified Schulthess classification of rheumatoid wrist involvement was used to classify the subtypes of wrist joint destruction radiographically types I, II, III, and IV, defined as ankylosing, osteoarthritis, disintegrating, and normal, respectively. We evaluated the wrist joints as stable or progressive by measuring the values of CHR and UTR indices. We also examined whether the modified Schulthess classification of rheumatoid wrist involvement subtypes are associated with radiographic progression over 10 years using the baseline CHR and UTR indices. RESULTS: The mean CHR values of types I and III were 0.42 (95% confidence interval [CI], 0.40-0.43) and 0.37 (95% CI, 0.34-0.39), respectively. The mean UTR values of types I and III were 0.348 (95% CI, 0.336-0.360) and 0.351 (95% CI, 0.339-0.367), respectively. These values indicated that degradation was faster in types I and III than in other types. We then found type I and III wrists to have progressive arthritis, and type II and IV wrists stable arthritis. We also found that the baseline CHR index was a significant (p < .05) predictor of radiographic progression. CONCLUSIONS: Our results indicated that type I and III wrists had radiographic progression and ultimately underwent deformation. This analysis also showed that the baseline CHR index was even more useful in predicting radiographic progression after 10 years.
20512337 Circadian rhythm and the influence of physical activity on circulating surfactant protein 2011 Dec Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed at assessing the diurnal rhythmicity and the influence of physical activity on circulating SP-D in patients with RA at different stages compared with healthy individuals. Patients with early RA (ERA) with disease duration <6 months and with long-standing RA (LRA) with disease duration 5-15 years were included in two sub-studies. Healthy individuals served as controls. Diurnal variation: blood samples were collected every 3 h from 7 a.m to 10 p.m and the following morning. Physical activity: blood sampling was done before and after standardized physical challenge. SP-D was measured by ELISA. SP-D exhibited diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P < 0.001, ERA: P = 0.004 and LRA: P = 0.009). Three hours after cessation of physical activity, SP-D decreased below pre-exercise levels in both ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P < 0.001, LRA: P < 0.001 and controls: P = 0.005). In patients with RA, the decline was already observed 1 h post-exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP-D in serum decreases following physical activity in health and RA disease. This study underscores the need of standardized blood sampling conditions in future studies on SP-D.
19260977 Bibliographical investigation of complementary alternative medicines for osteoarthritis an 2009 Mar BACKGROUND: A variety of complementary and alternative medicine (CAM) treatments are provided to the elderly. We investigated the efficacy and safety of CAM substances that are available to patients with osteoarthritis (OA) and rheumatoid arthritis (RA), both in Japan and overseas. METHODS: Information on CAM products was collected from the World Wide Web, using the keywords "arthritis" and "supplement" in five languages (Japanese, English, French, Italian and German) using a popular search engine for each of the languages. References to published work on the products were researched using PubMed with the keywords of "arthritis", "anti-inflammatory" and "analgesics". Such published work was classified according to the evidence levels established by the Cochrane Library. RESULTS: Two-hundred and sixty CAM products for OA or RA were available in Japan, of which 41 CAM products had been tested in randomized controlled trials (RCT); there was no scientific evidence for the remaining 219 CAM products. Most of the previous RCT suggested that CAM was effective in OA or RA. Herein, we confirmed the significant OA relieving effects of chondroitin sulfate through a meta-analysis. Effectiveness was assessed using subjective scores, not disease-specific immunological or serological markers for assessment. Toxicological investigations had only been performed for a few CAM products. CONCLUSION: Some CAM products that are effective against RA may be used together with biological therapy. However, some of the CAM products available in Japan should be tested using objective markers. Some CAM products for OA could be used for the relief of pain.
20369240 Rheumatoid arthritis masquerading as acromegaly recurrence: report of two cases. 2012 Sep Acromegaly is a chronic endocrinopathy characterized by hypersecretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). The arthropathy in acromegaly is the most frequent and important cause of morbidity and functional disability in acromegaly. Rheumatoid arthritis (RA) is a rarely reported clinical situation in patients with acromegalic. We herein report 57- and 45-year-old two women, who complained bilateral, symmetric pain, swelling and morning stiffness in the joints of hands after optimal acromegaly treatment resembling acromegaly arthropathy. There was not arthralgia in other joints of the patients. Laboratory and radiological evaluations were carried out. After excluding the acromegaly activation and arthropathy by GH and IGF-1 measurement, according to clinical presentation, laboratory and radiological assessments, patients were diagnosed as RA.
19555796 Depression increases risk of incident myocardial infarction among Veterans Administration 2009 Jul OBJECTIVE: This study evaluates whether depression is a risk factor for incident myocardial infarction (MI) in Department of Veterans Affairs (VA) patients with rheumatoid arthritis (RA) between 30 and 79 years of age. METHODS: We used a retrospective cohort study of 15,634 patients with RA. Diagnoses and sociodemographic data were obtained from VA administrative and pharmacy databases between fiscal years 1999 and 2006. Entry into the cohort required 2 years of patient time with no evidence of cardiovascular disease. Cox proportional hazard models with time-dependent covariates were computed to determine whether RA patients with depression as compared to RA patients without depression were at increased risk for MI during the maximum 6-year follow-up period. RESULTS: Unadjusted analyses indicated depressed RA patients were 1.4 times more likely than nondepressed RA patients to have an MI during follow-up. These results remained significant (HR=1.4; 95% CI: 1.1-1.8) in the adjusted Cox proportional hazards model which included the effects of sociodemographics and known physical risks (e.g., diabetes) for MI. CONCLUSIONS: Depressed RA patients, without a history of cardiovascular disease, are 40% more likely to have a heart attack as compared to those without depression. These data demonstrate a rapid (within 6 years) transition to MI following onset of depression in RA patients. Increased monitoring of depression and heart disease status in this patient population may be warranted which in turn may result in longer duration of life.
20151800 Association of periodontitis with rheumatoid arthritis: a pilot study. 2010 Feb BACKGROUND: Similarities exist in the epidemiology and immunopathogenesis of periodontitis and rheumatoid arthritis (RA), but the associations between their respective disease activities and severities are less well documented. We evaluated the prevalence and severity of periodontitis in United States (U.S.) veterans with RA and their relationship to RA disease activity and severity. METHODS: Patients with RA from an outpatient rheumatology clinic were eligible, and patients with osteoarthritis (OA) served as controls. Dentists, masked to the rheumatologic diagnoses, performed periodontal probing and examined dental panoramic radiographs to assess the presence and severity of periodontitis. Associations of periodontitis with RA were examined using multivariate regression, whereas the association of periodontitis with disease-severity measures in RA was examined using the chi(2) test. RESULTS: Sixty-nine patients with RA (57 males and 12 females) and 35 patients with OA (30 males and five females) were studied. Moderate to severe periodontitis was more prevalent in patients with RA (51%) than controls (26%) (P = 0.03), an association independent of age, race, smoking, diabetes mellitus, and gender. Patients with RA who were seropositive for rheumatoid factor (RF) were more likely to have moderate to severe periodontitis (59%) than patients who were RF negative (15%) (P = 0.02). Likewise, patients with RA who were positive for the anti-cyclic citrullinated peptide (CCP) antibodies were more likely to have moderate to severe periodontitis (56%) than patients who were anti-CCP negative (22%) (P = 0.01). There were no associations of periodontitis status with other measures of RA disease activity or severity. CONCLUSIONS: In a cohort of U.S. veterans, periodontitis was more common and severe in patients with RA compared to patients with OA. Although unrelated to disease activity, the presence of periodontitis in patients with RA was associated with seropositivity for RF and the anti-CCP antibody, which was highly relevant given the associations of these autoantibodies with poor outcomes and disease pathogenesis in RA.
20931346 The effects of strength and endurance training in patients with rheumatoid arthritis. 2011 May Patients with rheumatoid arthritis (RA) suffer from muscle loss, causing reduced muscle strength and endurance. The current study aimed to: (1) evaluate the effects of combined strength and endurance training (CT) on disease activity and functional ability in patients with RA and (2) investigate the benefits of a 6-month supervised CT program on muscle strength, cardio-respiratory fitness, and body composition of RA patients. Forty patients with RA, aged 41-73 years, were recruited for the current study. Twenty of these patients (19 females, one male) were randomly assigned to a 6-month supervised CT program; 20 patients (17 females, three males) served as controls. Within the CT program, strength training consisted of sets of weight bearing exercises for all major muscle groups. In addition to strength training, systematic endurance training was performed on a cycle ergometer two times per week. For RA patients involved in CT, disease activity (p = 0.06) and pain (p = 0.05) were reduced after the 6-month training period while general health (p = 0.04) and functional ability (p = 0.06) improved. Cardio-respiratory endurance was found to have improved significantly (by 10%) after 6 months of CT (p < 0.001). The overall strength of patients undertaking CT increased by an average of 14%. Lean body mass increased, and the percentage of body fat was found to decrease significantly (p < 0.05). A combination of strength and endurance training resulted in considerable improvements in RA patients' muscle strength and cardio-respiratory endurance, accompanied by positive changes in body composition and functional ability. Long-term training appears to be effective in reducing disease activity and associated pain and was found to have no deleterious effects.
19327235 The proteasome inhibitor bortezomib inhibits the release of NFkappaB-inducible cytokines a 2009 Jan OBJECTIVE: The proteasome is a multicatalytic proteinase complex regulating the intracellular breakdown of many proteins, including those mediating the activation of pro-inflammatory signaling pathways (e.g. NFkappaB), cell proliferation and survival. Conceptually, proteasome inhibitors may therefore elicit potential anti-inflammatory properties by inhibiting these processes and thereby impair the cellular release of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-alpha) in RA patients. METHODS: Whole-blood from 19 RA patients (including methotrexate-responsive and non-responsive patients) and 7 healthy volunteers was incubated ex-vivo with the proteasome inhibitor bortezomib after T-cell stimulation with alphaCD3/CD28. Inhibition of cytokine production by bortezomib was measured after 24 and 72 hours by ELISA. Effects of bortezomib on apoptosis and T-cell activation (CD25 expression) were measured by FACS-analysis. RESULTS: Bortezomib proved to be a rapid (<24 hour) and potent inhibitor of the release of several NFkappaB-inducible cytokines (including TNF-alpha, IL-1Beta, IL-6 and IL-10) by activated T-cells from healthy volunteers and RA patients, regardless of their clinical responsiveness to methotrexate. Median concentrations of bortezomib required to inhibit TNF-alpha production by 50% (mIC-50) were 12 nM (range: 8-50 nM) for healthy volunteers and 46 nM (range: 18-60 nM) for RA patients. A reduction of T cell activation and a marked induction of T-cell apoptosis were revealed as late effects after bortezomib incubations beyond 24 hours. CONCLUSION: Proteasome inhibitors represented by bortezomib may elicit potential anti-inflammatory properties that deserve further exploration in experimental therapies for RA.
19370385 A new low-field extremity magnetic resonance imaging and proposed compact MRI score: evalu 2009 Magnetic resonance imaging (MRI) is a useful tool for evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA). However, conventional whole-body MRI is inconvenient on several levels. We have therefore developed a new low-field extremity MRI (compact MRI, cMRI) and examined its clinical utility. Thirteen RA patients treated with anti-tumor necrosis factor (TNF) biologics were included in the study. The MRI was performed twice using a 0.21-T extremity MRI system. The MRI images were scored using our proposed cMRI scoring system, which we devised with reference to the Outcome Measures in Rheumatology Clinical Trials RA MRI score (OMERACT RAMRIS). In our cMRI scoring system, synovitis, bone edema, and bone erosion are separately graded on a scale from 0 to 3 by imaging over the whole hand, including the proximal interphalangeal joint. The total cMRI score (cMRIS) is then obtained by calculating the total bone erosion score x 1.5 + total bone edema score x 1.25 + total synovitis score. In this study, one patient showed a progression of bone destruction even under low clinical activity, as assessed by the disease activity score on 28 joints (DAS28); however, another patient's cMRIS decreased concurrently with the decrease in DAS28, with the positive correlation observed between DeltaDAS28 and DeltacMRIS (R = 0.055, P < 0.05). We conclude that cMRI and cMRIS are useful for assessing total disease activity and as a method linking MRI image evaluation to clinical evaluation.
19303802 Prevalence of subclinical amyloidosis in Tunisian patients with rheumatoid arthritis. 2009 May INTRODUCTION: Secondary amyloidosis is a serious complication of rheumatoid arthritis (RA). Symptoms are late to occur, so that screening is in order, most notably in patients with long-standing RA. The objectives of our study were to determine the prevalence of subclinical amyloidosis in RA patients by abdominal fat aspiration biopsy (AFAB) and minor salivary gland biopsy (MSGB) and to identify factors associated with subclinical amyloidosis. METHODS: We prospectively studied 107 consecutive patients with RA (94 women and 13 men) recruited between March 2005 and January 2006. Clinical and laboratory findings, imaging study results, and treatment were recorded for each patient. AFAB and MSGB were performed routinely. Amyloid deposits were identified by polarized light microscopy after Congo red staining. RESULTS: The prevalence of subclinical amyloidosis was 21.5% by AFAB and 3.7% by MSGB. Factors associated with subclinical amyloidosis were a longer time to diagnosis (P=0.03), extraarticular manifestations (P=0.019), proteinuria >0.3 g/24 h (P=0.024), and absence of methotrexate therapy (P=0.046). Subclinical amyloidosis was not associated with age, sex, RA duration, joint deformities, DAS28 score, Health Assessment Questionnaire score, Steinbrocker radiological stage, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, creatinine, or hemoglobin. CONCLUSION: The prevalence of subclinical amyloidosis by AFAB is high (21.5%). AFAB is more sensitive than MSGB for detecting subclinical amyloidosis. A simple screening tool such as AFAB should be used, particularly in patients with risk factors. Subclinical amyloidosis requires close monitoring to ensure the early detection and treatment of symptomatic amyloidosis.