Does a family history of RA influence the clinical presentation and treatment response in RA?

PubMed

Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

2016-06-01

To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset <12 months before inclusion, N=6869), and response to methotrexate (MTX) monotherapy in the subset starting this treatment (N=4630). Response to tumour necrosis factor inhibitors (TNFi) was examined among all patients with RA starting a TNFi as the first biological disease-modifying antirheumatic drug 2000-2011 (N=9249). Association of family history with clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

QUEST‐RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries

PubMed Central

Sokka, Tuulikki; Kautiainen, Hannu; Toloza, Sergio; Mäkinen, Heidi; Verstappen, Suzan M M; Hetland, Merete Lund; Naranjo, Antonio; Baecklund, Eva; Herborn, Gertraud; Rau, Rolf; Cazzato, Massimiliano; Gossec, Laure; Skakic, Vlado; Gogus, Feride; Sierakowski, Stanislaw; Bresnihan, Barry; Taylor, Peter; McClinton, Catherine; Pincus, Theodore

2007-01-01

Objective To conduct a cross‐sectional review of non‐selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. Methods The review included current disease activity using data from clinical assessment and a patient self‐report questionnaire, which was translated into each language. Data on demographic, disease and treatment‐related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28‐joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. Results Between January 2005 and October 2006, the QUEST‐RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 ⩽3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. Conclusions This international multicentre cross‐sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005–6 including countries that are infrequently involved in clinical research projects. PMID:17412740

Measurement of 224Ra and 226Ra activities in natural waters using a radon-in-air monitor

USGS Publications Warehouse

Kim, G.; Burnett, W.C.; Dulaiova, H.; Swarzenski, P.W.; Moore, W.S.

2001-01-01

We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn (218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

PubMed

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Second-hand exposure to tobacco smoke and its effect on disease activity in Swedish rheumatoid arthritis patients. Data from BARFOT, a multicenter study of RA.

PubMed

Söderlin, Maria K; Andersson, Maria; Bergman, Stefan

2013-01-01

We studied the prevalence and effect on disease activity of ever having had second-hand exposure to tobacco smoke in Swedish rheumatoid arthritis (RA) patients who had never smoked. Between 1992 and 2005, 2,800 patients were included in the BARFOT early-RA study in Sweden. Disease Activity Score 28 joints (DAS28), C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), rheumatoid factor (RF), general health and pain visual analogue scales (VAS), and drug treatment were registered at inclusion and at follow-up at 3, 6, and 12 months and 2 and 5 years. EULAR response criteria were applied at the same follow-up points. In 2010, a self-completion postal questionnaire was sent to 2,102 patients in the BARFOT study enquiring about lifestyle habits such as whether they had ever been exposed to tobacco smoke as a result of someone else smoking. A total of 963/1,421 patients (68%) had had second-hand exposure to tobacco smoke. At 3, 6, and 12 months, at 2 years, and at 5 years of follow-up, there were no differences in EULAR response between patients who had never smoked and who had been exposed or had not been exposed second-hand to tobacco smoke (p=0.91, p=0.88, p=0.84, p=0.61 and p=0.85, respectively). We did not find any association between second-hand exposure to tobacco smoke and disease activity in RA.

Prolong Exposure of NSAID in Patients With RA Will Decrease the Risk of Dementia

PubMed Central

Chang, Kuang-Hsi; Hsu, Yi-Chao; Hsu, Chih-Chao; Lin, Cheng-Li; Hsu, Chung Y.; Lee, Chang-Yin; Chong, Lee-Won; Liu, Hui-Chuan; Lin, Ming-Chia; Kao, Chia-Hung

2016-01-01

Abstract Rheumatoid arthritis (RA), a chronic, systemic inflammatory disorder, primarily affects joints. Several studies have indicated that early inflammation, cardiovascular disease, and depression in patients were associated with a considerably increased risk of dementia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for treating RA. NSAIDs facilitate alleviating RA-associated chronic pain, inflammation, and swelling. Therefore, we conducted this nationwide study for evaluating the association between the dementia risk and NSAID treatment in patients with RA. The RA cohort comprised patients aged 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database (RCIPD). Patients without RA were frequency matched with the RA cohort at a 1:4 ratio according to age, sex, and year of RA diagnosis. The relative risks of dementia were estimated using Cox proportional hazard models. The risk of dementia in the RA cohort was not significantly higher than that in the non-RA cohort (adjusted HR [hazard ratio] = 0.95, 95% confidence interval [CI] = 0.87–1.02). Regarding the duration of NSAID treatment, the risk of dementia was significantly lower when the RA cohort used NSAIDs for >2191 days (HR = 0.56, 95% CI = 0.45–0.68). A longer duration of NSAID treatment possibly reduces the risk of dementia. Additional studies are warranted for verifying the association of dementia risk with NSAID treatment in patients with RA. PMID:26962833

The Impact of Statin Use on Lipid Levels in Statin-Naive Patients with Rheumatoid Arthritis (RA) vs. non-RA Subjects: Results from a Population-Based Study

PubMed Central

Myasoedova, Elena; Gabriel, Sherine E.; Green, Abigail B.; Matteson, Eric L.; Crowson, Cynthia S.

2013-01-01

Objectives To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins. Methods Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 ACR criteria first met between 1/1/1988 and 1/1/2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included. Results The study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non-RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) were lower in RA vs non-RA cohort (p<0.001 and p=0.003, respectively). The absolute and percent change in LDL after at least 90 days of statin use tended to be smaller in RA vs non-RA cohort (p=0.03 and p=0.09). After at least 90 days of statin use patients with RA were less likely to achieve therapeutic goals for LDL than the non-RA subjects (p=0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (OR 0.47; 95% CI 0.26, 0.85) was associated with lower likelihood of achieving therapeutic LDL goals. Conclusion Patients with RA had lower TC and LDL levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non-RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals. PMID:23592565

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

PubMed Central

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-01-01

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

Secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis.

PubMed

Hanaoka, Beatriz Y; Ormseth, Michelle J; Michael Stein, C; Banerjee, Daipayan; Nikolova-Karakashian, Mariana; Crofford, Leslie J

2018-05-01

The goals of this study were to determine if secretory sphingomyelinase (S-SMase) activity is elevated in patients with rheumatoid arthritis (RA) compared to control subjects and to examine the relationships of S-SMase activity with functional status, quality of life, and RA disease activity measurements. We collected data on 33 patients who were diagnosed with RA and 17 non-RA controls who were comparable in terms of age, sex, and race. Demographic, clinical data and self-reported measures of fatigue, pain, and physical function were obtained directly from patients and controls. RA patients also completed quantitative joint assessment using a 28-joint count and functional status and quality of life assessment using the Modified Health Assessment Questionnaire (MHAQ). Archived serum samples were used to analyze retrospectively serum S-SMase activity in patients and controls. The mean serum S-SMase activity was 1.4-fold higher in patients with RA (RA 2.8 ± 1.0 nmol/ml/h vs. controls 2.0 ± 0.8 nmol/ml/h; p = 0.014). Spearman's rho correlations between S-SMase activity and oxidant activity, markers of inflammation and endothelial activation with the exception of P-selectin (rho = 0.40, p = 0.034), measures of disease activity, functional status, and quality of life were not statistically significant in patients with RA. We confirmed that S-SMase activity is higher among RA patients compared to controls, as in other acute and chronic inflammatory diseases. Future studies can build on the present findings to understand more fully the biologic role(s) of S-SMase activity in RA.

[The usefullness of hyaluronate injection in patients with RA].

PubMed

Saito, Seiji

2003-06-01

In this seminar, we reported the usefulness of hyaluronate injection in clinical application with patients of RA. In basic research areas, however, the mechanisms responsible for the reported beneficial clinical effects of these treatments remain unclear. There is accumulating experimental evidence to show that the receptors of HA, eg, CD-44, accelerate the inflammation of joint. Administration high molecular weight HA may modulate CD-44 sensitive macromolecular in joint inflammation in part to reduce the activity of proteinases such as MMP-9.

Impairment in immuno-modulatory function of Flk1(+)CD31(-)CD34(-) MSCs from MDS-RA patients.

PubMed

Han, Qin; Sun, Zhao; Liu, Lihui; Chen, Bin; Cao, Ying; Li, Kanghua; Zhao, Robert Chunhua

2007-11-01

Myelodysplastic syndromes are a group of hematopoietic disorders characterized by hematopoietic stem cell dysregulation and abnormalities in the immune system. Mesenchymal stem cells (MSCs) and their derived stromal cells constitute a bone marrow microenvironment, which is the niche for hematopoiesis and a key compartment for immune development and regulation. Existing evidence has shown that MSCs from MDS patients have impaired capacity in supporting hematopoiesis. Here, we conducted an investigation to determine whether the immuno-modulatory function of MSCs is also impaired in MDS-RA (refractory anemia) patients. Flk1(+)CD31(-)CD34(-) MSCs were isolated from 15 MDS-RA patients and cultured for testing biological and immunological characteristics. MDS-RA patient-derived Flk1(+)CD31(-)CD34(-) MSCs showed normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. In conclusion, MDS-RA patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for MDS.

Stages of change, barriers, benefits, and preferences for exercise in RA patients: a cross-sectional study.

PubMed

Henchoz, Y; Zufferey, P; So, A

2013-01-01

To determine the distribution of exercise stages of change in a rheumatoid arthritis (RA) cohort, and to examine patients' perceptions of exercise benefits, barriers, and their preferences for exercise. One hundred and twenty RA patients who attended the Rheumatology Unit of a University Hospital were asked to participate in the study. Those who agreed were administered a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. Eighty-nine (74%) patients were finally included in the analyses. Their mean age was 58.4 years, mean RA duration 10.1 years, and mean disease activity score 2.8. The distribution of exercise stages of change was as follows: precontemplation (n = 30, 34%), contemplation (n = 11, 13%), preparation (n = 5, 6%), action (n = 2, 2%), and maintenance (n = 39, 45%). Compared to patients in the maintenance stage of change, precontemplators exhibited different demographic and functional characteristics and reported less exercise benefits and more barriers to exercise. Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs different in terms of exercise counselling.

Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

PubMed

Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

2016-10-15

This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days. Copyright © 2016 Elsevier Ltd. All rights reserved.

Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia.

PubMed

Wolfe, Frederick; Michaud, Kaleb

2004-04-01

Fibromyalgia (FM) is a controversial construct. Recently suggested survey criteria identify persons with FM characteristics without physical examination or clinical diagnosis, thereby obviating many of the objections to FM. Little is known about FM among patients with rheumatoid arthritis (RAF). We used the survey definition to characterize persons with RAF and to obtain insight into possible pathogenic mechanisms. A total of 11,866 patients with RA completed the Regional Pain Scale (RPS) and a 0-10 visual analog scale (VAS) for fatigue. FM was diagnosed in patients with an RPS score > or = 8 and a VAS fatigue score > or = 6. Altogether 1731 (17.1%) patients with RA fulfilled the criteria. Fewer RAF patients were married (64.9% vs 69.8%) and more were divorced (14.8% vs 10.4%); fewer were college graduates (19.7% vs 28.1%) and more did not finish high school (15.0% vs 8.9%). We found 35.8% of patients with FM but only 21.5% of those without FM had incomes less than 185% of the US poverty guidelines. Patients with RAF had higher validated hospitalization rates for major comorbid conditions and received treatment for comorbid conditions more often (expressed as odds ratios and 95% confidence interval): hypertension (1.5, 1.4-1.7), cardiovascular (1.8, 1.6-2.0), diabetes (1.9, 1.6-2.3), and depression (2.7, 1.8-4.2). RAF were 3.3 (3.0-3.7) times more likely to have been work-disabled (54.5% vs 26.4%) or to have total joint replacement (14.0% vs 11.2%; OR 1.3, 1.1-1.5), and incurred greater direct 6-month medical costs (6477 vs 4687 US dollars). RAF patients had more severe symptoms across all scales, including the Health Assessment Questionnaire (1.8 vs 1.0), pain (6.7 vs 3.4), Medical Outcomes Study Short Form-36 (SF-36) physical component score (23.5 vs 33.5), SF-36 mental component score (29.5 vs 46.1), and quality of life assessed by EuroQol mapped utilities (0.33 vs 0.65). FM exists in a substantial number of patients with RA (17.1%), who have more severe RA by

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

PubMed

Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, P<0.001). Serum bilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

PubMed Central

Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

2018-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

Long-term blood pressure variability in patients with rheumatoid arthritis (RA) and its impact on cardiovascular events and all-cause mortality in RA: a population-based comparative cohort study

PubMed Central

Myasoedova, Elena; Crowson, Cynthia S.; Green, Abigail B.; Matteson, Eric L.; Gabriel, Sherine E.

2014-01-01

Objectives To examine long-term visit-to-visit blood pressure (BP) variability in rheumatoid arthritis (RA) vs non-RA subjects and to assess its impact on cardiovascular events and mortality in RA. Methods Clinic BP measures were collected in a population-based incident cohort of RA patients (1987 ACR criteria met between 1/1/1995 and 1/1/2008) and non-RA subjects. BP variability was defined as within-subject standard deviation (SD) in systolic and diastolic BP. Results Study included 442 RA patients (mean age 55.5 years, 70% females) and 424 non-RA subjects (mean age 55.7 years, 69% females). RA patients had higher visit-to-visit variability in systolic BP (13.8±4.7 mm Hg), than non-RA subjects (13.0±5.2 mm Hg, p=0.004). Systolic BP variability declined after the index date in RA (p<0.001), but not in the non-RA cohort (p=0.73), adjusting for age, sex and calendar year of RA. During the mean follow-up of 7.1 years, 33 cardiovascular events and 57 deaths occurred in RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of cardiovascular events (hazard ratio [HR] per 1 mm Hg increase in BP variability 1.12, 95% confidence interval [CI] 1.01-1.25); diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95%CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, use of antihypertensives. Conclusion Patients with RA had higher visit-to-visit systolic BP variability vs non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse cardiovascular outcomes and all-cause mortality in RA. PMID:24986852

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

PubMed

Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund; Aslam, Fawad; Khan, Nasim A; Jacobs, Johannes W G; Henrohn, Dan; Rasker, J J; Kauppi, Markku J; Lang, Hui-Chu; Mota, Licia M H; Aggarwal, Amita; Yamanaka, Hisahi; Badsha, Humeira; Gossec, Laure; Cutolo, Maurizio; Ferraccioli, Gianfranco; Gremese, Elisa; Bong Lee, Eun; Inanc, Nevsun; Direskeneli, Haner; Taylor, Peter; Huisman, Margriet; Alten, Rieke; Pohl, Christoph; Oyoo, Omondi; Stropuviene, Sigita; Drosos, Alexandrosos A; Kerzberg, Eduardo; Ancuta, Codorina; Mofti, Ayman; Bergman, Martin; Detert, Jaqueline; Selim, Zaraa I; Abda, Essam A; Rexhepi, Blerta; Sokka, Tuulikki

2014-01-01

The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants.

PubMed

Hartkamp, Linda M; Fine, Jay S; van Es, Inge E; Tang, Man Wai; Smith, Michael; Woods, John; Narula, Satwant; DeMartino, Julie; Tak, Paul P; Reedquist, Kris A

2015-08-01

Bruton's tyrosine kinase (Btk) is required for B lymphocyte and myeloid cell contributions to pathology in murine models of arthritis. Here, we examined the potential contributions of synovial Btk expression and activation to inflammation in rheumatoid arthritis (RA). Btk was detected by immunohistochemistry and digital image analysis in synovial tissue from biologically naive RA (n=16) and psoriatic arthritis (PsA) (n=12) patients. Cell populations expressing Btk were identified by immunofluorescent double labelling confocal microscopy, quantitative (q-) PCR and immunoblotting. The effects of a Btk-specific inhibitor, RN486, on gene expression in human macrophages and RA synovial tissue explants (n=8) were assessed by qPCR, ELISA and single-plex assays. Btk was expressed at equivalent levels in RA and PsA synovial tissue, restricted to B lymphocytes, monocytes, macrophages and mast cells. RN486 significantly inhibited macrophage IL-6 production induced by Fc receptor and CD40 ligation. RN486 also reduced mRNA expression of overlapping gene sets induced by IgG, CD40 ligand (CD40L) and RA synovial fluid, and significantly suppressed macrophage production of CD40L-induced IL-8, TNF, MMP-1 and MMP-10, LPS-induced MMP-1, MMP-7 and MMP-10 production, and spontaneous production of IL-6, PDGF, CXCL-9 and MMP-1 by RA synovial explants. Btk is expressed equivalently in RA and PsA synovial tissue, primarily in macrophages. Btk activity is needed to drive macrophage activation in response to multiple agonists relevant to inflammatory arthritis, and promotes RA synovial tissue cytokine and MMP production. Pharmacological targeting of Btk may be of therapeutic benefit in the treatment of RA and other inflammatory diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

RAPID3 scores and hand outcome measurements in RA patients: a preliminary study.

PubMed

Qorolli, Merita; Hundozi-Hysenaj, Hajrije; Rexhepi, Sylejman; Rehxepi, Blerta; Grazio, Simeon

2017-06-01

The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported disease activity measure used to assess physical function, pain, and global health in patients with rheumatoid arthritis (RA) without formal joint counts. Since hand involvement and its decreased function are hallmarks of RA, the aim of our study was to investigate the performance of RAPID3 scores with regard to hand function and to confirm previous findings that the RAPID3 score as a disease activity measure is strongly correlated with the DAS28 score. Sixty-eight consecutive patients with RA (85% female), aged 18-75 years, were included in the study and were recruited during their outpatient visit. Apart from demographic and clinical data, the obtained parameters of interest included RAPID3 scores and assessments of the function of the hand, namely, the signal of functional impairment (SOFI)-hand, grip strength, and pulp-to-palm distance, as well the Health Assessment Questionnaire- Disability Index (HAQ-DI) and DAS28 scores. Pearson's correlation coefficient, Student's t test and linear regression were used in the statistical analysis of the results. The significance was set to p < 0.05. A positive correlation was found between RAPID3 scores and HAQ-DI scores, SOFI-hand scores, and pulp-to-palm distance, and negative correlation was observed between RAPID3 scores and grip strength. The order regarding the strength of correlations between RAPID3 scores and other variables (from the strongest to the weakest) was as follows: HAQ-DI, grip strength, SOFI-hand and pulp-to-palm distance. The hand assessment variables had stronger correlations with RAPID3 scores than with DAS28 scores. Our preliminary study showed that RAPID3 scores were strongly correlated with measurements of the functional ability of the hand, demonstrating that RAPID3 can be used as a measure of disease activity in clinical practice and to characterize hand function. Further studies are needed to confirm this result.

Clinical characteristics of RA patients with secondary SS and association with joint damage.

PubMed

Brown, Lindsay E; Frits, Michelle L; Iannaccone, Christine K; Weinblatt, Michael E; Shadick, Nancy A; Liao, Katherine P

2015-05-01

Secondary SS (sSS) is a common extra-articular manifestation of RA. There are conflicting data regarding the association of sSS with worse joint damage. This study aims to characterize sSS patients in an RA cohort and study the association between sSS and joint damage. We conducted a cross-sectional study of RA patients with ≥1 year of follow-up at a large academic centre. Subjects with co-morbid diseases that can also result in sicca symptoms were excluded from the analysis. Subjects were considered to have sSS if they were reported as having sSS by their rheumatologist at recruitment into the cohort and had the diagnosis confirmed by chart review. The primary outcome was Sharp score using bilateral hand radiographs at recruitment. We constructed a linear regression model to determine the association of sSS status and Sharp score adjusted by age, gender, disease duration and ACPA and RF status. We studied 829 RA subjects, mean age 57 years, 83% female, mean RA duration 13 years, 74% seropositive; 85 subjects (10.3%) had sSS. We observed a female predominance (95.3%), longer mean disease duration (16.9 years) and higher frequency of RF or ACPA positive among patients with sSS and RA. Having sSS at baseline was associated with higher Sharp scores (P = 0.03), independent of age, gender, RA disease duration and seropositive disease. In our RA cohort, RA subjects with sSS had worse joint damage, suggesting that sSS is a marker of more aggressive disease. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vitamin D status and its association with quality of life, physical activity, and disease activity in rheumatoid arthritis patients.

PubMed

Raczkiewicz, Anna; Kisiel, Bartłomiej; Kulig, Maciej; Tłustochowicz, Witold

2015-04-01

Vitamin D deficiency is common in rheumatoid arthritis (RA) and may be related to disease activity. Population-based studies have shown the influence of vitamin D deficiency on quality of life (QoL), but it was not investigated in RA patients. The aim of the study was to determine possible relationship between vitamin D deficiency, QoL, physical activity (PA), and disease activity in RA. In 97 consecutive RA patients without vitamin D supplementation (86 women and 11 men, aged 59.4 ± 12 years), serum 25-hydroxycholecalciferol (25(OH)D), calcium, phosphorus, and parathyroid hormone were measured. The patients completed Short Form 36 (SF-36), Beck Depression Inventory, and Health Assessment Questionnaire, assessed the intensity of pain, fatigue, and PA. Disease Activity Score in 28 Joints was used to assess disease activity. A comparison control group consisted of 28 osteoarthritis patients (25 women and 3 men aged 56.2 ± 15 years). Vitamin D deficiency was detected in 76.3% of RA and in 78.6% of osteoarthritis patients (P = 0.75). There was a negative correlation between 25(OH)D serum concentration and Disease Activity Score in 28 Joints in patients with active arthritis. There was a positive correlation between serum 25(OH)D and the level of PA and most aspects of SF-36, and negative correlation between serum 25(OH)D and Health Assessment Questionnaire and Beck Depression Inventory in patients with disease duration of 1 year or longer. After inclusion of PA into multivariable analysis, only the correlations between 25(OH)D and SF-36 mental subscale (MCS) and pain remained significant. Vitamin D deficiency is highly prevalent in RA patients and is associated with higher disease activity and worse QoL indices. Regular PA correlates with higher vitamin D titers and better QoL in RA. Further studies are needed to explain possible influence of vitamin D on RA activity.

Rheumatoid arthritis patients with active disease and no history of cardiac pathology have higher brain natriuretic peptide (BNP) levels than patients with inactive disease or healthy control subjects.

PubMed

Armstrong, D J; Gardiner, P V; O'Kane, M J

2010-05-01

Rheumatoid arthritis (RA) is associated with increased incidence cardiac failure. It is yet unclear how much the increased incidence is secondary to ischaemic damage, or whether inflammatory cytokines might have a direct effect on the myocardium. To establish if patients with active rheumatoid arthritis but no history of cardiac disease have higher serum levels of brain natriuretic peptide (BNP), than patients with less active RA, or disease-free controls. 90 patients with RA and 31 healthy control subjects were recruited. Each was screened to exclude previous history of cardiac disease. RA disease activity was measured using the DAS28 assessment, and other demographic, physical and laboratory tests performed. Serum BNP levels were measured in all subjects. There was no difference in the age, percentage females or BMI between the RA and control subjects. Median BNP in the RA patients was 80.0 pg/ml (IQR 38.0-132.0) compared with 48.5 (26.0-86.0) in the control subjects (p=0.017). There was a significant correlation between DAS28 and serum BNP in the RA group, r=0.37, p<0.01. RA patients were divided into three groups according to DAS28 scores. Patients with very active disease (DAS28>5.1) had significantly higher BNP levels than patients with moderately active disease (3.2RA patients with inactive disease did not differ from Controls. RA patients with no history of cardiac disease have higher serum BNP levels than healthy control subjects. RA patients with active RA have higher BNP levels than RA patients with moderately active or inactive disease, raising the possibility of a directly depressive effect of inflammatory cytokines on the myocardium.

Role of physical activity in the management and assessment of rheumatoid arthritis patients.

PubMed

Hernández-Hernández, María Vanesa; Díaz-González, Federico

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting diarthrodial joints, in which patients tend to perform less physical activity (PA) than recommended. This review focuses on the existing evidence about the relationship of PA and RA, specifically how the former influences joint inflammation, disability, quality of life and pain in RA patients, and also how disease activity potentially impacts PA in these patients. A literature search of EMBASE and MEDLINE databases from January 2000 to January 2015. The evidence indicating that PA in RA patients is safe and the benefits from regularly performing, both aerobic and resistance exercises, in these patients include improvement in: quality of life, functionality, pain and number of swollen joints. Interestingly, recent studies suggest that changes in disease activity in RA patients inversely correlate with variations in PA, as assessed by accelerometry. The regular monitoring of PA in RA patients might facilitate a more objective evaluation of variations in disease activity, helping physicians to make general and therapeutic recommendations that will improve both the health status and the joint functionality of these patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

atRA-induced apoptosis of mouse embryonic palate mesenchymal cells involves activation of MAPK pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Zengli; Xing Ying

2006-08-15

Our previous studies have shown that atRA treatment resulted in cell-cycle block and growth inhibition in mouse embryonic palatal mesenchymal (MEPM). In the current study, gestation day (GD) 13 MEPM cells were used to test the hypothesis that the growth inhibition by atRA is due to apoptosis. The effects of atRA on apoptosis were assessed by performing MTT assay, Cell Death Detection ELISA and flow cytometry, respectively. Data analysis confirmed that atRA treatment induced apoptosis-like cell death, as shown by decreased cell viability and increased fragmented DNA and sub-G1 fraction. atRA-induced apoptosis was associated with upregulation of bcl-2, translocation ofmore » bax protein to the mitochondria from the cytosol, activation of caspase-3 and cytochrome c release into cytosol. atRA-induced apoptosis was abrogated by z-DEVD-fmk, a caspase-3 specific inhibitor, and z-VAD-fmk, a general caspase inhibitor, suggesting that the atRA-induced cell death of MEPM cells occurs through the cytochrome c- and caspase-3-dependent pathways. In addition, atRA treatment caused a strong and sustained activation of c-Jun N-terminal kinase (JNK) and p38 kinase (p38), as well as an early but transient activation of extracellular signal-regulated kinase (ERK). Importantly, atRA-induced DNA fragmentation and capase-3 activation were prevented by pretreatment with the JNK inhibitor (SP600125) and the p38 MAPK inhibitor (SB202190), but not by pretreatment with MEK inhibitor (U0126). From these results, we suggest that mitogen-activated protein kinase-dependent pathways is involved in the atRA-induced apoptosis of MEPM cells.« less

Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co-existent bronchiectasis.

PubMed

Perry, Elizabeth; Eggleton, Paul; De Soyza, Anthony; Hutchinson, David; Kelly, Clive

2017-12-01

Patients with rheumatoid arthritis (RA) and co-existent bronchiectasis (BRRA) have a five-fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. However, RA disease activity measures such as Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have not been studied, so we assessed these parameters in patients with BRRA and RA alone. BRRA patients (n = 53) had high-resolution computed tomography proven bronchiectasis without any interstitial lung disease and ≥ 2 respiratory infections/year. RA alone patients (n = 50) had no clinical or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor (immunoglobulin M) and anti-CCP were measured in all patients, together with detailed clinical and radiology records. In BRRA, bronchiectasis predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti-CCP (89% vs. 46%) and rheumatoid factor (79% vs. 52%) (P = 0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (P = 0.003). There were no significant differences between groups in smoking history or disease-modifying anti-rheumatic drug/biologic therapy. Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co-existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Physical Activity Assessment Using an Activity Tracker in Patients with Rheumatoid Arthritis and Axial Spondyloarthritis: Prospective Observational Study

PubMed Central

Servy, Hervé; Molto, Anna; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Fautrel, Bruno; Gossec, Laure

2018-01-01

Background Physical activity can be tracked using mobile devices and is recommended in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) management. The World Health Organization (WHO) recommends at least 150 min per week of moderate to vigorous physical activity (MVPA). Objective The objectives of this study were to assess and compare physical activity and its patterns in patients with RA and axSpA using an activity tracker and to assess the feasibility of mobile devices in this population. Methods This multicentric prospective observational study (ActConnect) included patients who had definite RA or axSpA, and a smartphone. Physical activity was assessed over 3 months using a mobile activity tracker, recording the number of steps per minute. The number of patients reaching the WHO recommendations was calculated. RA and axSpA were compared, using linear mixed models, for number of steps, proportion of morning steps, duration of total activity, and MVPA. Physical activity trajectories were identified using the K-means method, and factors related to the low activity trajectory were explored by logistic regression. Acceptability was assessed by the mean number of days the tracker was worn over the 3 months (ie, adherence), the percentage of wearing time, and by an acceptability questionnaire. Results A total of 157 patients (83 RA and 74 axSpA) were analyzed; 36.3% (57/157) patients were males, and their mean age was 46 (standard deviation [SD] 12) years and mean disease duration was 11 (SD 9) years. RA and axSpA patients had similar physical activity levels of 16 (SD 11) and 15 (SD 12) min per day of MVPA (P=.80), respectively. Only 27.4% (43/157) patients reached the recommendations with a mean MVPA of 106 (SD 77) min per week. The following three trajectories were identified with constant activity: low (54.1% [85/157] of patients), moderate (42.7% [67/157] of patients), and high (3.2% [5/157] of patients) levels of MVPA. A higher body mass index was

(226) RA AND (228) RA ACTIVITIES ASSOCIATED WITH AGRICULTURAL DRAINAGE PONDS AND WETLAND PONDS IN THE KANKAKEE WATERSHED, IL-IN, USA

EPA Science Inventory

Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-a and -B activities were measured up to 455 and 1650 mBq L-1, respectively. 226Ra and 228Ra averaged 139 and 192 mBq L-01...

Nociceptive Afferent Activity Alters the SI RA Neuron Response to Mechanical Skin Stimulation

PubMed Central

Favorov, O.V.; Li, Y.; Lee, J.; Quibrera, P.M.; Tommerdahl, M.

2010-01-01

Procedures that reliably evoke cutaneous pain in humans (i.e., 5–7 s skin contact with a 47–51 °C probe, intradermal algogen injection) are shown to decrease the mean spike firing rate (MFR) and degree to which the rapidly adapting (RA) neurons in areas 3b/1 of squirrel monkey primary somatosensory cortex (SI) entrain to a 25-Hz stimulus to the receptive field center (RFcenter) when stimulus amplitude is “near-threshold” (i.e., 10–50 μm). In contrast, RA neuron MFR and entrainment are either unaffected or enhanced by 47–51 °C contact or intradermal algogen injection when the amplitude of 25-Hz stimulation is 100–200 μm (suprathreshold). The results are attributed to an “activity dependence” of γ-aminobutyric acid (GABA) action on the GABAA receptors of RA neurons. The nociceptive afferent drive triggered by skin contact with a 47–51 °C probe or intradermal algogen is proposed to activate nociresponsive neurons in area 3a which, via corticocortical connections, leads to the release of GABA in areas 3b/1. It is hypothesized that GABA is hyperpolarizing/inhibitory and suppresses stimulus-evoked RA neuron MFR and entrainment whenever RA neuron activity is low (as when the RFcenter stimulus is weak/near-threshold) but is depolarizing/excitatory and augments MFR and entrainment when RA neuron activity is high (when the stimulus is strong/suprathreshold). PMID:20308203

Motivation as a determinant of physical activity in patients with rheumatoid arthritis.

PubMed

Hurkmans, E J; Maes, S; de Gucht, V; Knittle, K; Peeters, A J; Ronday, H K; Vlieland, T P M Vliet

2010-03-01

A sufficient level of physical activity is important in reducing the impact of disease in rheumatoid arthritis (RA) patients. According to self-determination theory, the achievement and maintenance of physical activity is related to goal setting and ownership, which can be supported by health professionals. Our objective was to examine the association between physical activity and the extent to which RA patients 1) believe that physical activity is a goal set by themselves (autonomous regulation) or by others (coerced regulation) and 2) feel supported by rheumatologists (autonomy supportiveness). A random selection of 643 RA patients from the outpatient clinics of 3 hospitals were sent a postal survey to assess current physical activity level (Short Questionnaire to Assess Health-Enhancing Physical Activity), regulation style (Treatment Self-Regulation Questionnaire), and the autonomy supportiveness of their rheumatologists (modified Health Care Climate Questionnaire). Of the 271 patients (42%) who returned the questionnaire, 178 (66%) were female, their mean +/- SD age was 62 +/- 14 years, and their mean +/- SD disease duration was 10 +/- 8 years. Younger age, female sex, higher education level, shorter disease duration, lower disease activity, and a more autonomous regulation were univariately associated with more physical activity. Hierarchical multiple regression analyses demonstrated that younger age and a more autonomous regulation were significantly associated with a higher physical activity level (P = 0.000 and 0.050, respectively). Regulation style was a significant determinant of physical activity in RA patients. This finding may contribute to further development of interventions to enhance physical activity in RA patients.

Correlation of Paraoxonase Status with Disease Activity Score and Systemic Inflammation in Rheumatoid Arthritic Patients.

PubMed

Bindal, Usha Dudeja; Saxena, Rahul; Siddiqui, Merajul Haque; Sharma, Dilutpal

2016-03-01

Despite, various preventive efforts on conventional cardiovascular disease (CVD) risk factors, the incidence of CVD in rheumatoid arthritis (RA) patients increases continuously. To solve this conundrum one needs more investigations. The present study was conducted to evaluate the plasma paraoxonase (PON) activity along with the markers of systemic inflammation, oxidative stress and disease activity score-28 (DAS28) in RA patients and clarify their role in determining the probability of RA patients to develop future CVD risk. Plasma PON, total antioxidant activity (TAA), C-reactive protein (CRP), synovial interleukin-6 (IL-6) and erythrocyte malondialdehyde (MDA) levels were estimated in 40 RA patients aged 40-55 years aged and 40 age-matched healthy controls. The data obtained were compared statistically by using Student's t-test and Pearson correlation test. Besides dyslipidaemia, marked reduction in plasma PON and TAA (p< 0.05) were observed in RA patients as compared with that of healthy controls. Erythrocyte MDA, plasma CRP and synovial IL-6 levels were increased significantly (p<0.05) in RA patients. PON was negatively correlated with MDA (r = - 0.672; p < 0.001), CRP (r = -0.458; p<0.05), IL-6 (r = -0.426; p<0.05) and DAS28 (r = -0.598; p < 0.001), and positively correlated with HDL cholesterol (r = 0.648; p<0.001) and TAA (r = 0.608; p< 0.001) levels in RA patients. Alteration in PON activity might contribute to the progression of future CVD risk in RA patients, which may result from interplay of several confounding factors, such as inflammation, oxidative stress and dyslipidaemia. Furthermore, plasma PON activity, CRP and TAA levels could be considered as non-traditional factors to predict CVD risk. Thus, it is suggested that future drugs could be developed to target the non-traditional risk factors in RA patients.

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study

PubMed Central

Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel A; Calvo-Alén, Jaime; Hørslev-Petersen, Kim; Luukkainen, Reijo K; Combe, Bernard; Burmester, Gerd R; Devlin, Joe; Ferraccioli, Gianfranco; Morelli, Alessia; Hoekstra, Monique; Majdan, Maria; Sadkiewicz, Stefan; Belmonte, Miguel; Holmqvist, Ann-Carin; Choy, Ernest; Tunc, Recep; Dimic, Aleksander; Bergman, Martin; Toloza, Sergio; Pincus, Theodore

2008-01-01

Introduction We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. Methods The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. Results Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

PubMed

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

2017-08-01

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

The relationship between disease activity, quality of life, and personality types in rheumatoid arthritis and ankylosing spondylitis patients.

PubMed

Donisan, T; Bojincă, V C; Dobrin, M A; Bălănescu, D V; Predețeanu, D; Bojincă, M; Berghea, F; Opriș, D; Groșeanu, L; Borangiu, A; Constantinescu, C L; Ionescu, R; Bălănescu, A R

2017-07-01

We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.

Analytical study of 226Ra activity concentration in market consuming foodstuffs of Ramsar, Iran.

PubMed

Gooniband Shooshtari, M; Deevband, M R; Kardan, M R; Fathabadi, N; Salehi, A A; Naddafi, K; Yunesian, M; Nabizadeh Nodehi, R; Karimi, M; Hosseini, S S

2017-01-01

Ramsar, a city of Iran located on the coast of the Caspian Sea, has been considered to be enormously important due to its high natural radioactivity levels. People living in High Level Natural Radiation Areas (HLNRAs) have been exposed by several sources, one of which could be foodstuff. However, many studies have been carried out to measure the environmental radioactivity in Ramsar, but no survey has been conducted in all stapled consumed foods yet. This study was dedicated to determine 226 Ra activity concentration in the daily diets of Ramsar residents as a probable exposure. Approximately 70 different market samples were collected during the four seasons based on the daily consumption patterns of residents which have the highest consumption and their availability in the seasons. All samples, after washing, drying and pretreatment, were analyzed for 226 Ra radionuclide determination by α-spectrometry. The mean radioactivity concentration of 226 Ra ranged between 7 ± 1 mBq Kg -1 wet weight in meat, and 318 ± 118 mBq Kg -1 for tea dry leaves. The 226 Ra activity concentrations in collected samples varied from below the minimum detectable activity up to 530 ± 30 mBq Kg -1 . To compare the results with United Nations Scientific Committee on Effects of Atomic Radiation (UNSCEAR) reference values, the 226 Ra activity concentrations concluded from the results appear to be higher in milk, chicken and eggs and less in grain products, vegetables, fruits and fish products. These results indicate that no significant 226 Ra contamination is present in market foodstuffs and provide reference values for the foodstuffs in Ramsar. Of the total daily dietary 226 Ra exposure from market consuming foodstuffs for adults in Ramsar, the largest percentage was from wheat. The residents consuming wheat and manufacturing wheat products such as bread, pasta, porridge, crackers, biscuits, pancakes, pies, pastries, cakes, cookies, muffins, rolls, doughnuts, breakfast cereals and

Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs.

PubMed

Naredo, Esperanza; Möller, Ingrid; Corrales, Alfonso; Bong, David A; Cobo-Ibáñez, Tatiana; Corominas, Hector; Garcia-Vivar, Ma Luz; Macarrón, Pilar; Navio, Teresa; Richi, Patricia; Iagnocco, Annamaria; Garrido, Jesús; Martínez-Hernández, David

2013-02-01

To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P < 0.0005). The mean CCA-IMT was significantly greater in RA patients treated only with synthetic DMARDs than in controls [591.4 (98.6) vs 562.1 (85.8); P = 0.035] and in RA patients treated with synthetic and biologic DMARDs [591.4 (98.6) vs 558.8 (95.3); P = 0.040). There was no significant difference between the mean CCA-IMT in RA patients treated with synthetic and biologic DMARDs and controls (P = 0.997). Our results suggest that radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons

PubMed Central

Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

2016-01-01

Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. PMID:26904300

Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons.

PubMed

Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

2016-01-01

Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production.

Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis

PubMed Central

Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof

2017-01-01

Introduction Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. Material and methods We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. Results There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04–2.28; p = 0.035). Conclusions The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity. PMID:28883856

[Correlation of DNase I in serum and synovial fluid with inflammatory activity in patients with rheumatoid arthritis].

PubMed

Xu, Xia-Yu; Yang, Wen-Fang; Zhang, Si-Gong; Zhao, Qin; Linag, Li-Jun; Wang, Xin; Shen, Hai-Li

2016-08-20

To investigate the potential role of deoxyribonuclease I (DNase I) in the pathogenesis of rheumatoid arthritis (RA). DNase I activity was measured by radial enzyme-diffusion method in serum samples from 83 RA patients and 60 healthy volunteers and in the synovial fluid (SF) from 27 RA patients and 38 patients with other inflammatory arthritis. SF cfDNA level was measured with Pico Green Kit, and the correlation among DNase I activity, cfDNA level and clinical parameters of RA patients was analyzed. Serum DNase I activity was significantly lower in RA patients than in the healthy control subjects (0.3065∓0.1436 vs 0.4289∓0.1976 U/mL, P<0.001), and was negatively correlated with ESR (r=-0.2862, P=0.0122), CRP (r=-0.2790, P=0.0184) and neutrophil cell counts (r=-0.287, P=0.011). SF DNase I activity was almost negative in patients with RA, ankylosing spondylitis (AS) and gouty arthritis (GA). SF cfDNA level in RA patients was significantly higher than that in patients with osteoarthritis (100.81∓142.98 vs 18.98∓31.40 µg/mL, P=0.002), but similar to that in patients with AS (45.85∓47.67 µg/mL, P=0.428) and GA (162.95∓97.49 µg/mL, P=0.132). In patients with inflammatory arthritis, SF cfDNA level was positively correlated with ESR (r=0.4106, P=0.0116) and CRP (r=0.5747, P=0.0002). Impairment of DNase I activity may be responsible for the enhanced NETs generation and plays a role in the pathogenesis of RA.

[Active forms of oxygen and nitrogen in blood cells of patients with rheumatoid arthritis: effect of laser therapy].

PubMed

Ostrakhovich, E A; Ilich-Stoianovich, O; Afanas'ev, I B

2001-01-01

Infrared pulse laser therapy was studied for its impact on the production of active forms of oxygen and nitrogen by neutrophils from patients with rheumatoid arthritis (RA). The authors determined the non-activated and PMA-activated production of superoxide anion-radical, peroxynitrite, peripheral neurophilic NAD.PH-oxidase and superoxide dismutase activities, and the red blood cell concentrations of reduced glutathione. Before therapy, non-activation RA neurophilic production of superoxide was much higher than in donors. Laser therapy made this parameter normal. Similarly, neutrophilic peroxynitrite production (defined by dihydrorhodamine oxidation) in RA patients was 1.7 times higher than the normal values. IF-laser therapy decreased peroxynitrite production to the values observed in donors. It is important that the therapy caused increased SOD activity (that was lower in RA patients prior to therapy) up to apparently control values. Thus, IF-laser therapy has a certain antioxidative effect by increasing SOD activity in RA patients' blood cells and reducing the production of highly reactive oxygen and nitrogen forms.

Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

DTIC Science & Technology

2017-04-26

REV1E\\\\’ER 50. "E PFlEV101JS EOmC»lS ARE C . E1E ?~e 3 01 3 FlIll!!S D ~.!!fitt Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA...Background • Rheumatoid arthritis - Affecting 1-3 million Americans - Seventy percent are women - Associated with higher risk of heart disease and stroke...and Objectives Purpose: Assess medication adherence in patients with rheumatoid arthritis Objectives: 1. Primary: Assess whether there is a correlation

Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics.

PubMed

Frisell, Thomas; Baecklund, Eva; Bengtsson, Karin; Di Giuseppe, Daniela; Forsblad-d'Elia, Helena; Askling, Johan

2018-05-01

With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome. Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011-2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006-2010. Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably. There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs' safety and effectiveness. © Article author(s) (or their employer(s) unless otherwise stated in the text

228Ra and 226Ra Profiles from the Northern South China Sea

NASA Astrophysics Data System (ADS)

Lin, H.; Chung, Y.; Lin, C.

2005-05-01

We previously reported the distributions of 228Ra and 226Ra in the northern South China Sea (SCS) which showed that both nuclides in surface waters were much higher than those in the open oceans because the SCS was enclosed mostly by landmasses which are known as sources of these nuclides. Large temporal and spectial variations were also observed probably due to the monsoons and intrusion of the Kuroshio Current. During a recent cruise conducted in the northern SCS in February, 2004, three vertical 228Ra profiles were measured by gamma spectrometry on the Ra isotopes which were concentrated first by the MnO2-impregnated acrylic fiber and then acid-washed as sample solution for counting. The two deep water 228Ra profiles are remarkably similar, showing high values in the surface layer and fairly uniform at about 10 to 13 dpm/100L below 200m depth but with a clear increase toward the bottom due to input from the underlying sediments. The shallow water profile on the shelf shows higher 228Ra values due to both vertical and horizontal mixing of the shelf water with additional source from the shore zone. Additional 228Ra profiles measured on samples from earlier cruises show that the deep water values may differ significantly (up to 5 dpm/100L) at the same location in different seasons or cruises. The associated 226Ra profiles are also variable but quite comparable to those in the northwest Pacific in deep water. 226Ra activities in the shallow water (less than 1000m depth) are higher in the SCS than in the open oceans. The 228Ra/226Ra activity ratios vary mostly from about 0.3 to 0.5 in the deep water. These values are much higher than those in the open oceans which are generally less than 0.1.

Role of interleukin-23 as a biomarker in rheumatoid arthritis patients and its correlation with disease activity.

PubMed

Zaky, Doaa S E; El-Nahrery, Eslam M A

2016-02-01

IL-23 is a pro-inflammatory cytokine belonging to the IL-12 cytokine family. IL-23 is essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implicated in chronic inflammatory/autoimmune mediated diseases. Experimental models of arthritis and clinical indications have highlighted an important role for Th17 lymphocytes in the pathogenesis of RA. However the role and mechanism of action of IL-23 in the pathogenesis of RA are still not fully understood. This study was conducted to assess the level of IL-23 in patients with RA as well as the relationship between the IL-23 level and disease activity. The study includes 77 patients with RA fulfilling the American College of Rheumatology (ACR) revised criteria for diagnosis of RA as well as 25 age and sex matched healthy subjects as controls. Patients were divided according to disease activity into four groups: DAS 28 score (˂ 2.6), 10 patients in remission, DAS 28 score between 2.6-3.2, 10 patients with low disease activity, DAS 28 score ranges between (3.2-5.1), 30 patients with moderate disease activity and DAS 28 score (˂ 5.1), 27 patients with High disease activity. Disease activity were determined by the 28-joint disease activity score (DAS 28). Anti-citrullinated protein antibodies (ACPA) was done. The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA). Serum level of IL-23 was significantly elevated in RA patients (78.92±52.47) compared to control group (33.34±3.99) (P<0.001). However, no correlations were found between IL-23 and DAS 28 score, and other patients characteristics. Our results imply that IL-23 may potentially play a role in the pathogenesis of RA and may be a useful biomarker for the diagnosis of this disease. Targeting the IL-23 cytokine may provide a new therapeutic approach in the treatment of RA. Copyright © 2015 Elsevier B.V. All rights reserved.

Preferential reduction of bone mineral density at the femur reflects impairment of physical activity in patients with low-activity rheumatoid arthritis.

PubMed

Sugiguchi, Shigeru; Goto, Hitoshi; Inaba, Masaaki; Nishizawa, Yoshiki

2010-02-01

Bone mineral density (BMD) and factors influencing BMD in rheumatoid arthritis (RA) under good or moderate control were examined to assess management of osteoporosis in RA. BMD of the lumbar spine, femur, and distal radius was measured in 105 female patients with well-controlled RA. Laboratory and clinical variables associated with disease activity were measured in the same subjects, and correlations between these variables and BMD were evaluated. The RA patients showed a greater decrease in BMD of the femoral neck than of the lumbar spine. Age, Health Assessment Questionnaire (HAQ) score, and Larsen damage score had negative correlations with BMD of the femoral neck. In multiple regression analysis of the parameters associated with BMD of the femoral neck in simple regression analysis, an increase in HAQ score showed a negative correlation with BMD of the femoral neck. After initiation of treatment with alendronate (ALN), BMD of the femoral neck increased and correlated with improvement in HAQ score. A decrease in BMD of the femoral neck is a characteristic of RA. This suggests that muscle tonus has more effect than weight-bearing activity on BMD in patients with RA. BMD of the femoral neck is a useful index for general evaluation of RA patients.

Microbial release of 226Ra2+ from (Ba,Ra)SO4 sludges from uranium mine wastes.

PubMed Central

Fedorak, P M; Westlake, D W; Anders, C; Kratochvil, B; Motkosky, N; Anderson, W B; Huck, P M

1986-01-01

226Ra2+ is removed from uranium mine effluents by coprecipitation with BaSO4. (Ba,Ra)SO4 sludge samples from two Canadian mine sites were found to contain active heterotrophic populations of aerobic, anaerobic, denitrifying, and sulfate-reducing bacteria. Under laboratory conditions, sulfate reduction occurred in batch cultures when carbon sources such as acetate, glucose, glycollate, lactate, or pyruvate were added to samples of (Ba,Ra)SO4 sludge. No external sources of nitrogen or phosphate were required for this activity. Further studies with lactate supplementation showed that once the soluble SO4(2-) in the overlying water was depleted, Ba2+ and 226Ra2+ were dissolved from the (Ba,Ra)SO4 sludge, with the concurrent production of S2-. Levels of dissolved 226Ra2+ reached approximately 400 Bq/liter after 10 weeks of incubation. Results suggest that the ultimate disposal of these sludges must maintain conditions to minimize the activity of the indigenous sulfate-reducing bacteria to ensure that unacceptably high levels of 226Ra2+ are not released to the environment. PMID:3752993

Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study.

PubMed

Kume, Kensuke; Amano, Kanzo; Yamada, Susumu; Kanazawa, Toshikatsu; Ohta, Hiroyuki; Hatta, Kazuhiko; Amano, Kuniki; Kuwaba, Noriko

2017-12-01

Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active RA (28-joint disease activity score-erythrocyte sedimentation rate > 3.2) despite methotrexate (MTX) treatment 12 mg/week were included in this open-label prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day). Japanese guideline does not allow high dose of MTX. All patients used a stable dosage of MTX, steroids, and statins or lipid-lowering drugs. The primary endpoint was the comparison of the carotid intima-media thickness (CIMT) at the baseline and 54 weeks after Tofa treatment. Clinical data were collected at regular visits. Forty-six patients completed this study. CIMT did not significantly change from baseline to 54 weeks (1.09 ± 0.69 and 1.08 ± 0.78 mm, p = 0.82). In 12 patients who had atherosclerosis at baseline (carotid intima-media thickness > 1.10 mm), there was a significant decrease in CIMT (0.05± 0.026 mm; p < 0.05). However, the decrease in CIMT was of limited clinical significance. Tofacitinib increased fasting total cholesterol levels from baseline to 54 weeks (216 ± 25.3 and 234 ± 28.8 mg/dL, p < 0.01). Tofacitinib affects atherosclerosis in patients with active RA The CIMT in RA patients was stable. Tofacitinib decreased the CIMT of patients who had increased CIMT at baseline. Tofacitinib reduced RA disease activity and limited vascular damage despite up-regulating cholesterol in patients with an active RA.

226Ra activity in the mullet species Liza aurata and South Adriatic Sea marine.

PubMed

Antovic, N M; Antovic, I; Svrkota, N

2010-08-01

(226)Ra activity in the South Adriatic Sea-water, surface sediment, mud with detritus, seagrass (Posidonia oceanica) samples and the mullet (Mugilidae) species Liza aurata, as well as soil and sand from the Montenegrin Coast-was measured using the six-crystal gamma-coincidence spectrometer PRIPYAT-2M. The results are used for calculation of the absorbed (and annual effective) dose rates in air due to the (226)Ra gamma radiation. The absorbed dose rates ranged from 5.94 to 97.16 nGy h(-1) (soil) and from 0.65 to 7.65 nGy h(-1) (sand). In seawater (226)Ra activity is found to be from 0.08 to 0.15 Bq l(-1), while in whole L. aurata individuals from 0.58 to 1.97 Bq kg(-1). Annual intake of (226)Ra by human consumers of this fish species has been estimated to provide an effective dose of 0.006 mSv y(-1).

Ra-226 bioaccumulation and growth indices in fish.

PubMed

Shi, Xiaopei; Smith, Richard; Seymour, Colin; Mothersill, Carmel

2017-06-01

To determine the accumulated activity of Ra-226 in fathead minnows fed with environmentally relevant levels of Ra-226 for 5 months in water at 20 °C, and to evaluate the influence of this level of Ra-226 on the growth of fathead minnows. Fathead minnows were fed with fish food containing 10-10,000 mBq/g Ra-226 for 5 months. At the end of the experiment, the fish were sacrificed, flash frozen in liquid nitrogen and kept at -20 °C. Longitudinal sections of 40 μm thickness were cut at the middle of the fish body using a cryostat. The activity of Ra-226 in each section was determined using autoradiography with a nuclear track detector CR-39. According to the weight and the width of the fish, the activity of Ra-226 in the whole fish body could be estimated. In addition, the length and the weight of the fish were measured and the condition factor was calculated to evaluate the growth and fitness of the fish. There is a positive but non-linear relationship between the accumulated activity of Ra-226 in fish body and the concentration of Ra-226 in fish food. The highest activity of Ra-226 accumulated in fish body was found from fish fed with 10,000 mBq/g Ra-226 food. This was calculated as 256.4 ± 49.1 mBq/g, p < 0.05, and the calculated dose rate was 6.2 ± 1.2 mGy/y. For fish fed with food containing lower concentration of Ra-226 (up to 1000 mBq/g), the bioaccumulation of Ra-226 in the body saturated. The Ra-226 concentration factor (CF) for fish was inversely proportional to the Ra-226 activity in food, and the highest CF value was 2.489, obtained from the lowest dietary Ra-226 activity (10 mBq/g). In addition, condition factors (K) of fish in all Ra-226-treated groups were significantly lower than those of the controls. The results show that the bioaccumulation of Ra-226 in fish is not simply related to the dietary Ra-226 activity, and has a saturation value when the dietary activity is low. In addition, the environmental level of Ra-226 in the fish

[Influence of physical treatment on disease activity and health status of patients with chronic arthritis].

PubMed

Mustur, Dusan; Vujasinović-Stupar, Nada; Ille, Tatjana

2008-01-01

This is an open uncontrolled study about effects of physical treatment on disease activity parameters of patients with rheumatoid arthritis and psoriatic arthritis. The aim of the study was to establish if there was any improvement of disease activity parameters after four weeks of physical and spa treatment. We compared morning stiffness, tender and swollen joint count, body pain level and Disease Activity Score 28 (DAS-28) in patients with rheumatoid and psoriatic arthritis, and assessed the effect of physical and spa treatment on those parameters. The research encompassed 109 patients: 69 with rheumatoid arthritis (RA group) and 40 with psoriatic arthritis (PA group). They were from Norway, staying for four weeks in June-September 2003. The groups served as their own controls--"one group pre-test post test" study. Disease activity measurement was made twice: at the beginning and at the end of treatment. The therapeutic set consisted of mud applications, kinesitherapy, mineral water pool and electrotherapy. At the beginning there was no significant difference in observed disease activity parameters between patients with rheumatoid and psoriatic arthritis (p > 0.05). After four weeks of physical and spa treatment disease activity was significantly reduced in all observed parameters in both groups: morning stiffness (p < 0.001 RA + PA), tender joint count (p < 0.01 RA + PA), swollen joint count (p < 0.01 RA; p < 0.05 PA), body pain (p < 0.01 RA + PA) and DAS-28 score (p < 0.01 RA+PA). Physical and spa treatment, together with climatic factors in Igalo, lead to a significant reduction of disease activity parameters of patients suffering from rheumatoid arthritis and psoriatic arthritis.

Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients.

PubMed

Goertz, B; Fassbender, W J; Williams, J C; Marzeion, A M; Bretzel, R G; Stracke, H; Berliner, M N

2003-01-01

Vitamin D is known to exert immunomodulatory effects. An overrepresentation of the b allele of the vitamin D receptor (VDR) has been detected in autoimmune diseases as type-1-diabetes and multiple sclerosis. VDR polymorphisms have been shown to influence bone metabolism and bone density. The aim of the present study was to examine the distribution of VDR alleles in German rheumatoid arthritis (RA) patients and their relation to bone turnover parameters. 62 German RA patients were included and compared to 40 controls. Three VDR alleles were examined (Bsm I, Taq I and Fok I). In addition, serum intact osteocalcin (OC), parathyroid hormone, bone specific alkaline phosphatase (B-ALP), the carboxyterminal extension peptide of type I procollagen, 25-OH-vitamin D and urinary deoxypyridinoline (DPD) excretion were measured. Furthermore, C-reactive protein, erythrocyte sedimentation rate and rheumatoid factor were measured. We found a slightly higher frequency of the bB and tT-genotype in RA patients compared to controls, which was not statistically significant. OC and B-ALP were found to be significantly higher in RA patients with positive correlations between bone formation and resorption parameters indicating higher bone turnover in RA patients with maintained coupling. CRP in RA patients correlated with DPD and inversely with PTH. VDR genotype showed no association with bone turnover, family history or the presence of rheumatoid factor. Our results suggest that VDR polymorphisms do not play a major role in RA predisposition in Germans.

The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria.

PubMed

Buntinas, L; Gunter, K K; Sparagna, G C; Gunter, T E

2001-04-02

A mechanism of Ca(2+) uptake, capable of sequestering significant amounts of Ca(2+) from cytosolic Ca(2+) pulses, has previously been identified in liver mitochondria. This mechanism, the Rapid Mode of Ca(2+) uptake (RaM), was shown to sequester Ca(2+) very rapidly at the beginning of each pulse in a sequence [Sparagna et al. (1995) J. Biol. Chem. 270, 27510-27515]. The existence and properties of RaM in heart mitochondria, however, are unknown and are the basis for this study. We show that RaM functions in heart mitochondria with some of the characteristics of RaM in liver, but its activation and inhibition are quite different. It is feasible that these differences represent different physiological adaptations in these two tissues. In both tissues, RaM is highly conductive at the beginning of a Ca(2+) pulse, but is inhibited by the rising [Ca(2+)] of the pulse itself. In heart mitochondria, the time required at low [Ca(2+)] to reestablish high Ca(2+) conductivity via RaM i.e. the 'resetting time' of RaM is much longer than in liver. RaM in liver mitochondria is strongly activated by spermine, activated by ATP or GTP and unaffected by ADP and AMP. In heart, RaM is activated much less strongly by spermine and unaffected by ATP or GTP. RaM in heart is strongly inhibited by AMP and has a biphasic response to ADP; it is activated at low concentrations and inhibited at high concentrations. Finally, an hypothesis consistent with the data and characteristics of liver and heart is presented to explain how RaM may function to control the rate of oxidative phosphorylation in each tissue. Under this hypothesis, RaM functions to create a brief, high free Ca(2+) concentration inside mitochondria which may activate intramitochondrial metabolic reactions with relatively small amounts of Ca(2+) uptake. This hypothesis is consistent with the view that intramitochondrial [Ca(2+)] may be used to control the rate of ADP phosphorylation in such a way as to minimize the probability of

Multibiomarker disease activity score and C-reactive protein in a cross-sectional observational study of patients with rheumatoid arthritis with and without concomitant fibromyalgia.

PubMed

Lee, Yvonne C; Hackett, James; Frits, Michelle; Iannaccone, Christine K; Shadick, Nancy A; Weinblatt, Michael E; Segurado, Oscar G; Sasso, Eric H

2016-04-01

To examine the association between a multibiomarker disease activity (MBDA) score, CRP and clinical disease activity measures among RA patients with and without concomitant FM. In an observational cohort of patients with established RA, we performed a cross-sectional analysis comparing MBDA scores with CRP by rank correlation and cross-classification. MBDA scores, CRP and clinical measures of disease activity were compared between patients with RA alone and RA with concomitant FM (RA and FM) by univariate and multivariate analyses. CRP was ⩽1.0 mg/dl for 184 of 198 patients (93%). MBDA scores correlated with CRP (r = 0.755, P < 0.001), but were often discordant, being moderate or high for 19%, 55% and 87% of patients with CRP ⩽0.1, 0.1 to ⩽0.3, or 0.3 to ⩽1.0 mg/dl, respectively. Among patients with CRP ⩽1.0 mg/dl, swollen joint count (SJC) increased linearly across levels of MBDA score, both with (P = 0.021) and without (P = 0.004) adjustment for CRP, whereas CRP was not associated with SJC. The 28-joint-DAS-CRP, other composite measures, and their non-joint-count component measures were significantly greater for patients with RA and FM (n = 25) versus RA alone (n = 173) (all P ⩽ 0.005). MBDA scores and CRP were similar between groups. MBDA scores frequently indicated RA disease activity when CRP did not. Neither one was significantly greater among patients with RA and FM versus RA alone. Thus, MBDA score may be a useful objective measure for identifying RA patients with active inflammation when CRP is low (⩽1.0 mg/dl), including RA patients with concomitant FM. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Complement activating properties of complexes containing rheumatoid factor in synovial fluids and sera from patients with rheumatoid arthritis.

PubMed Central

Elson, C J; Carter, S D; Cottrell, B J; Scott, D G; Bacon, P A; Wallington, T B

1985-01-01

The relationship between complexes containing rheumatoid factor and complexes activating complement was examined in synovial fluids and sera from patients with rheumatoid arthritis (RA). In each case this was performed by quantifying the amount of rheumatoid factor bound by solid phase Fab'2 anti-C3 and/or solid phase conglutinin. Both anti-C3 coated and conglutinin coated microtitre plates bound high levels of complexes containing rheumatoid factor from sera of RA patients with vasculitis. Unexpectedly, these complexes were detected in synovial fluids from only a minority of RA patients with synovitis. However, RA synovial fluids did contain other complexes as shown by the presence of complement consuming activity, C1q binding material and immunoglobulin attaching to conglutinin. It is considered that in RA synovial fluids the complexes containing RF and those activating complement are not necessarily the same whilst in vasculitic sera the complexes containing rheumatoid factor also activate complement. PMID:3978872

Power of national economy, disease control and employment status in patients with RA-an analytical multi-site ecological study.

PubMed

Pieringer, Herwig; Puchner, Rudolf; Pohanka, Erich; Danninger, Kathrin

2016-02-01

In rheumatology, sufficient disease control is a central part of the treatment concept. However, modern treatment strategies are associated with a substantial economic burden for health care systems. Ecological studies offer the unique opportunity to analyse differences between groups as well as group level effects. In the present analytical multi-site ecological study, we investigated whether more powerful national economies as measured by the gross domestic product per capita (GDPpc) are associated with better disease control in RA patients as measured by the disease activity score 28 (DAS28). We used aggregated data on RA patients from the recently published COMORA study as well as the World Health Organization database. There was a strong negative correlation between DAS28 and GDPpc (r = -0.815; p = 0.0002). Adjustment for sex, smoking status, disease duration or current employment status did not significantly change this association. There was a strong, negative correlation between DAS28 and age (r = -0.870; p < 0.001) and a strong, positive correlation between GDPpc and age (r = 0.737; p = 0.002). Adjustment for age reduced the regression coefficient (DAS28/GDPpc) to -0.000018 (p = 0.054). There was a negative correlation between DAS28 and current employment status (r = -0.642; p = 0.008) and a positive correlation between GDPpc and employment status (r = 0.722; p = 0.002). In conclusion, there is evidence of an association between disease control and GDPpc. This association is alleviated after adjustment for age. Of note, in countries with higher GDPpc, a higher proportion of RA patients are currently employed. This is true despite the fact that RA patients in countries with higher GDPpc are also older.

Activated complement components and complement activator molecules on the surface of cell‐derived microparticles in patients with rheumatoid arthritis and healthy individuals

PubMed Central

Biró, Éva; Nieuwland, Rienk; Tak, Paul P; Pronk, Loes M; Schaap, Marianne C L; Sturk, Augueste; Hack, C Erik

2007-01-01

Objectives In vitro, microparticles can activate complement via the classical pathway. If demonstrable ex vivo, this mechanism may contribute to the pathogenesis of rheumatoid arthritis (RA). We therefore investigated the presence of activated complement components and complement activator molecules on the surface of cell‐derived microparticles of RA patients and healthy individuals. Methods Microparticles from synovial fluid (n = 8) and plasma (n = 9) of 10 RA patients and plasma of sex‐ and age‐matched healthy individuals (n = 10) were analysed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C‐reactive protein (CRP), serum amyloid P component (SAP), immunoglobulin (Ig) M, IgG). Results Microparticles with bound C1q, C4, and/or C3 were abundant in RA synovial fluid, while in RA and control plasma much lower levels were present. Microparticles with bound C1q correlated with those with bound C3 in synovial fluid (r = 0.961, p = 0.0001), and with those with bound C4 in plasma (RA: r = 0.908, p = 0.0007; control: r = 0.632, p = 0.0498), indicating classical pathway activation. In synovial fluid, microparticles with IgM and IgG correlated with those with C1q (r = 0.728, p = 0.0408; r = 0.952, p = 0.0003, respectively), and in plasma, microparticles with CRP correlated with those with C1q (RA: r = 0.903, p = 0.0021; control: r = 0.683, p = 0.0296), implicating IgG and IgM in the classical pathway activation in RA synovial fluid, and CRP in the low level classical pathway activation in plasma. Conclusions This study demonstrates the presence of bound complement components and activator molecules on microparticles ex vivo, and supports their role in low grade complement activation in plasma and increased complement activation in RA synovial fluid. PMID:17261534

Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response

PubMed Central

Obry, Antoine; Hardouin, Julie; Lequerré, Thierry; Jarnier, Frédérique; Boyer, Olivier; Fardellone, Patrice; Philippe, Peggy; Marcelli, Christian; Loët, Xavier Le; Vittecoq, Olivier; Cosette, Pascal

2015-01-01

Objective: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. Methods: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic “label free” approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. Results: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. Conclusion: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation. PMID:26379787

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Joint positions matter for ultrasound examination of RA patients-increased power Doppler signal in neutral versus flat position of hands.

PubMed

Husic, Rusmir; Lackner, Angelika; Stradner, Martin H; Hermann, Josef; Dejaco, Christian

2017-08-01

Position of joints might influence the result of US examination in patients with RA. The purpose of this work was to compare grey-scale (GS) and power Doppler (PWD) findings obtained in neutral vs flat position of hands. A cross-sectional study of 42 RA patients with active disease. Two dimensional and 3D sonography of wrists and MCP joints were conducted in two different joint positions: neutral position, which is a slight flexion of the fingers with relaxed extensor muscles; and flat position, where all palm and volar sides of fingers touch the Table. Two dimensional GS synovitis (GSS) and PWD signals were scored semi-quantitatively (0-3). For 3D sonography, the percentage of PWD voxels within a region of interest was calculated. GSS was not quantified using 3D sonography. Compared with neutral position, 2D PWD signals disappeared in 28.3% of joints upon flattening. The median global 2D PWD score (sum of all PWD scores of an individual patient) decreased from 8 to 3 ( P < 0.001), and the global 3D PWD voxel score from 3.8 to 0.9 ( P < 0.001). The reduction of PWD scores was similar in all joints (2D: minus 50%, 3D: minus 66.4-80.1%). Inter- and intrareader agreement of PWD results was good (intraclass correlation coefficient: 0.75-0.82). In RA, a neutral position of the hands is linked to a higher sensitivity of 2D and 3D sonography in detecting PWD signals at wrists and MCP joints, compared with a flat position. Standardization of the scanning procedure is essential for obtaining comparable US results in RA patients in trials and clinical routines. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency

PubMed Central

Lévy, Romain; Okada, Satoshi; Béziat, Vivien; Moriya, Kunihiko; Liu, Caini; Chai, Louis Yi Ann; Migaud, Mélanie; Hauck, Fabian; Al Ali, Amein; Cyrus, Cyril; Vatte, Chittibabu; Patiroglu, Turkan; Unal, Ekrem; Ferneiny, Marie; Hyakuna, Nobuyuki; Nepesov, Serdar; Oleastro, Matias; Ikinciogullari, Aydan; Dogu, Figen; Asano, Takaki; Ohara, Osamu; Yun, Ling; Della Mina, Erika; Bronnimann, Didier; Itan, Yuval; Gothe, Florian; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Tahuil, Natalia; Aytekin, Caner; Salhi, Aicha; Al Muhsen, Saleh; Kobayashi, Masao; Toubiana, Julie; Abel, Laurent; Li, Xiaoxia; Camcioglu, Yildiz; Celmeli, Fatih; Klein, Christoph; AlKhater, Suzan A.; Casanova, Jean-Laurent; Puel, Anne

2016-01-01

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC—autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency—was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface. PMID:27930337

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale, Prospective, Single-Cohort ANOUVEAU Study.

PubMed

Takeuchi, Tsutomu; Nakajima, Ryo; Komatsu, Shuichi; Yamazaki, Kiyotaka; Nakamura, Tomohiro; Agata, Naoki; Igarashi, Ataru; Tango, Toshiro; Tanaka, Yoshiya

2017-03-01

The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan. Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness. Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%. Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA. AbbVie GK and Eisai Co., Ltd. ClinicalTrials.gov identifier, NCT01346488.

Silymarin (Livergol®) Decreases Disease Activity Score in Patients with Rheumatoid Arthritis: A Non-randomized Single-arm Clinical Trial.

PubMed

Shavandi, Mehrdad; Moini, Ali; Shakiba, Yadollah; Mashkorinia, Ahamad; Dehghani, Milad; Asar, Shirin; Kiani, Amir

2017-04-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which can lead to joint destruction and disability. Pannus formation due to chronic synovitis is the hallmark of RA. Oxidative stress as a consequence of immune cell activation and disease-modifying anti-rheumatic drugs can prevent inflammation and tissue destruction. Silymarin, an antioxidant extract from Silybum marianum, has been traditionally used for the treatment of liver diseases for decades. In the present non-randomized single-arm clinical trial (NRSACT) study we evaluated the effects of silymarin tablet (Livergol®) on inflammatory markers in stable RA patients. Disease activity score (DAS-28) was measured before and after adding silymarin to standard drug regimen used for controlling inflammation in RA patients. Silymarin significantly reduced the DAS28 related symptoms in 44 RA patients after 90 days (3.02±0.98 versus 2.3±0.74, p<0.001). The exact mechanism of therapeutic effects of silymarin in RA patients is not clear but it could be as the results of its anti-inflammatory and anti-oxidative properties. Conducting the study on larger number of patients and also measuring cytokines levels including TNF-α and IL-1β may clarify the underlying mechanisms of the anti-inflammatory effects of silymarin in RA patients.

Seasonal changes in submarine groundwater discharge to coastal salt ponds estimated using 226Ra and 228Ra as tracers

USGS Publications Warehouse

Hougham, A.L.; Moran, S.B.; Masterson, J.P.; Kelly, R.P.

2008-01-01

Submarine groundwater discharge (SGD) to coastal southern Rhode Island was estimated from measurements of the naturally-occurring radioisotopes 226Ra (t1/2 = 1600??y) and 228Ra (t1/2 = 5.75??y). Surface water and porewater samples were collected quarterly in Winnapaug, Quonochontaug, Ninigret, Green Hill, and Pt. Judith-Potter Ponds, as well as nearly monthly in the surface water of Rhode Island Sound, from January 2002 to August 2003; additional porewater samples were collected in August 2005. Surface water activities ranged from 12-83??dpm 100??L- 1 (60??dpm = 1??Bq) and 21-256??dpm 100??L- 1 for 226Ra and 228Ra, respectively. Porewater 226Ra activities ranged from 16-736??dpm 100??L- 1 (2002-2003) and 95-815??dpm 100??L- 1 (2005), while porewater 228Ra activities ranged from 23-1265??dpm 100??L- 1. Combining these data with a simple box model provided average 226Ra-based submarine groundwater fluxes ranging from 11-159??L m- 2 d- 1 and average 228Ra-derived fluxes of 15-259??L m- 2 d- 1. Seasonal changes in Ra-derived SGD were apparent in all ponds as well as between ponds, with SGD values of 30-472??L m- 2 d- 1 (Winnapaug Pond), 6-20??L m- 2 d- 1 (Quonochontaug Pond), 36-273??L m- 2 d- 1 (Ninigret Pond), 29-76??L m- 2 d- 1 (Green Hill Pond), and 19-83??L m- 2 d- 1 (Pt. Judith-Potter Pond). These Ra-derived fluxes are up to two orders of magnitude higher than results predicted by a numerical model of groundwater flow, estimates of aquifer recharge for the study period, and values published in previous Ra-based SGD studies in Rhode Island. This disparity may result from differences in the type of flow (recirculated seawater versus fresh groundwater) determined using each technique, as well as variability in porewater Ra activity. ?? 2007 Elsevier B.V. All rights reserved.

Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis.

PubMed

Kuusela, Elina; Kouri, Vesa-Petteri; Olkkonen, Juri; Koivuniemi, Riitta; Äyräväinen, Leena; Rajamäki, Kristiina; Valleala, Heikki; Nordström, Dan; Leirisalo-Repo, Marjatta; Ainola, Mari; Eklund, Kari K

2018-03-20

To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity. The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28). At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA. Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries.

PubMed

Askling, Johan; Berglind, Niklas; Franzen, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D; Ho, Meilien; Holmqvist, Marie; Horne, Laura; Inoue, Eisuke; Michaud, Kaleb; Nyberg, Fredrik; Pappas, Dimitrios A; Reed, George; Tanaka, Eiichi; Tran, Trung N; Verstappen, Suzanne M M; Yamanaka, Hisashi; Wesby-van Swaay, Eveline; Symmons, Deborah

2016-10-01

The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effect of certolizumab pegol with methotrexate on home and work place productivity and social activities in patients with active rheumatoid arthritis.

PubMed

Kavanaugh, Arthur; Smolen, Josef S; Emery, Paul; Purcaru, Oana; Keystone, Edward; Richard, Lance; Strand, Vibeke; van Vollenhoven, Ronald F

2009-11-15

To assess the impact of certolizumab pegol (CZP), a novel PEGylated anti-tumor necrosis factor, in combination with methotrexate (MTX) on productivity outside and within the home, and on participation in family, social, and leisure activities in adult patients with rheumatoid arthritis (RA). The efficacy and safety of CZP (200 mg and 400 mg) plus MTX were assessed in 2 phase III, multicenter, double-blind, placebo-controlled trials (Rheumatoid Arthritis Prevention of Structural Damage [RAPID] 1 and RAPID 2). The novel, validated, RA-specific Work Productivity Survey (WPS-RA) was used to assess work place and home productivity. WPS-RA responses were collected at baseline and every 4 weeks until withdrawal/study completion. At baseline, 41.6% and 39.8% of subjects were employed outside the home in RAPID 1 and RAPID 2, respectively. Compared with placebo plus MTX, CZP plus MTX significantly reduced work absenteeism and presenteeism among patients working outside the home. Significant reductions in number of household days lost, household days with productivity reduced by >/=50%, and days lost due to RA for participation in family, social, and leisure activities were reported by patients in active treatment relative to placebo plus MTX. Improvements in all measures were observed with CZP plus MTX as early as week 4, and maintained until the study end (12 months in RAPID 1, 6 months in RAPID 2). Findings were consistent with clinical improvements with CZP plus MTX in both trials. CZP plus MTX improved productivity outside and within the home and resulted in more participation in social activities compared with placebo plus MTX. These observations suggest that considerable indirect cost gains might be achieved with this therapeutic agent in RA.

Perceived Barriers, Facilitators and Benefits for Regular Physical Activity and Exercise in Patients with Rheumatoid Arthritis: A Review of the Literature.

PubMed

Veldhuijzen van Zanten, Jet J C S; Rouse, Peter C; Hale, Elizabeth D; Ntoumanis, Nikos; Metsios, George S; Duda, Joan L; Kitas, George D

2015-10-01

Rheumatoid arthritis (RA) is an autoimmune disease, which not only affects the joints but can also impact on general well-being and risk for cardiovascular disease. Regular physical activity and exercise in patients with RA have numerous health benefits. Nevertheless, the majority of patients with RA are physically inactive. This indicates that people with RA might experience additional or more severe barriers to physical activity or exercise than the general population. This narrative review provides an overview of perceived barriers, benefits and facilitators of physical activity and exercise in RA. Databases were searched for articles published until September 2014 using the terms 'rheumatoid arthritis', 'physical activity', 'exercise', 'barriers', 'facilitators', 'benefits', 'motivation', 'motivators' and 'enablers'. Similarities were found between disease-specific barriers and benefits of physical activity and exercise, e.g. pain and fatigue are frequently mentioned as barriers, but reductions in pain and fatigue are perceived benefits of physical activity and exercise. Even though exercise does not influence the existence of barriers, physically active patients appear to be more capable of overcoming them. Therefore, exercise programmes should enhance self-efficacy for exercise in order to achieve long-term physical activity and exercise behaviour. Encouragement from health professionals and friends/family are facilitators for physical activity and exercise. There is a need for interventions that support RA patients in overcoming barriers to physical activity and exercise and help sustain this important health behaviour.

Impact of tocilizumab on N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis without cardiac symptoms.

PubMed

Yokoe, I; Kobayashi, H; Kobayashi, Y; Giles, J T; Yoneyama, K; Kitamura, N; Takei, M

2018-05-28

To prospectively investigate the effect of tocilizumab (TCZ) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), as a predictor of congestive heart failure (CHF) in patients with active rheumatoid arthritis (RA). Seventy patients with RA (median age 59 years, 86% female) free of cardiovascular disease were treated with TCZ and followed for 24 weeks. The NT-proBNP levels were measured at baseline and week 24. Thirty healthy controls were included for comparison of normal NT-proBNP levels with those of RA patients. The NT-proBNP level was significantly higher in patients with RA than in controls (median 42.5 pg/mL vs 109.0 pg/mL, p < 0.001). NT-proBNP levels decreased by 63% over the 24 weeks of TCZ treatment. Multiple linear regression analysis indicated that the percentage change in the NT-proBNP level was significantly associated with that of the Simplified Disease Activity Index (β = 0.356, p = 0.014), even after adjusting for the levels of rheumatoid factor, duration of RA, age, and anti-cyclic citrullinated peptide antibody. TCZ decreased the NT-proBNP level in patients with RA without preceding cardiovascular disease and CHF. TCZ may have a cardioprotective effect in those with active RA.

Value of body mass index in the diagnosis of obesity according to DEXA in well-controlled RA patients.

PubMed

Tello-Winniczuk, Nina; Vega-Morales, David; García-Hernandez, Pedro A; Esquivel-Valerio, Jorge A; Garza-Elizondo, Mario A; Arana-Guajardo, Ana C

Rheumatoid arthritis (RA) has an indirect effect on body composition. Body mass index (BMI) is not a valid predictor of body fat in RA patients. To evaluate the accuracy of BMI in identifying obesity diagnosed according to dual energy X-ray absorptiometry (DXA) in well-controlled RA patients. An observational, cross-sectional, descriptive, analytical study. We used 3 different cutoffs for obesity as determined by DXA: >35% total fat, >40% total fat, and >35% central fat mass (central obesity). One hundred one patients were included. We found that 35% total fat corresponded to a BMI of 24kg/m 2 , with a sensitivity of 90% and specificity of 75% (area under the curve [AUC] 0.917); 40% total fat to a BMI of 25kg/m 2 , with a sensitivity of 86% and specificity of 39% (AUC 0.822); and 35% central fat mass to a BMI of 22kg/m 2 , with a sensitivity of 97% and specificity of 84% (AUC 0.951). Obesity according to DXA was underdiagnosed when the classic BMI cutoffs were used in well-controlled RA patients. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Gene expression analysis in RA: towards personalized medicine

PubMed Central

Burska, A N; Roget, K; Blits, M; Soto Gomez, L; van de Loo, F; Hazelwood, L D; Verweij, C L; Rowe, A; Goulielmos, G N; van Baarsen, L G M; Ponchel, F

2014-01-01

Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patient's care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients. PMID:24589910

Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen activator inhibitor-2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy.

PubMed

Kurgan, Ş; Önder, C; Balcı, N; Fentoğlu, Ö; Eser, F; Balseven, M; Serdar, M A; Tatakis, D N; Günhan, M

2017-06-01

The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study.

PubMed

Jacquemin, Charlotte; Molto, Anna; Servy, Hervé; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Granger, Benjamin; Fautrel, Bruno; Gossec, Laure

2017-01-01

The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%-21% and an absolute decrease ranging from 836 to 1462 steps/day. Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares.

A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer.

PubMed

Parker, Christopher C; Pascoe, Sarah; Chodacki, Aleš; O'Sullivan, Joe M; Germá, Josep R; O'Bryan-Tear, Charles Gillies; Haider, Trond; Hoskin, Peter

2013-02-01

Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile. To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases. In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the proportion of patients in each dose group who had a confirmed decrease of ≥ 50% in baseline prostate-specific antigen (PSA) levels. Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups. The study met its primary end point with a statistically significant dose-response relationship in confirmed ≥ 50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p=0.0297). A ≥ 50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p<0.0001). The most common treatment-related AEs (≥ 10%) occurring up to week 24 across all dose groups were diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic events was seen among dose groups. Potential limitations include small patient numbers and differences among dose groups at baseline. Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223

Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type.

PubMed

Schau, Thomas; Gottwald, Michael; Arbach, Olga; Seifert, Martin; Schöpp, Maren; Neuß, Michael; Butter, Christian; Zänker, Michael

2015-11-01

Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 ± 13 yrs) from our outpatient clinic and in 77 age- and sex-matched controls. The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score ≥ 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs -19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies.

Can baseline ultrasound results help to predict failure to achieve DAS28 remission after 1 year of tight control treatment in early RA patients?

PubMed

Ten Cate, D F; Jacobs, J W G; Swen, W A A; Hazes, J M W; de Jager, M H; Basoski, N M; Haagsma, C J; Luime, J J; Gerards, A H

2018-01-30

At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1-5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05-0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89-1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p = 0.31). In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. Clinicaltrials.gov, NCT01752309 . Registered on 19 December 2012.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

PubMed

Sokka, Tuulikki; Kautiainen, Hannu; Pincus, Theodore; Verstappen, Suzanne M M; Aggarwal, Amita; Alten, Rieke; Andersone, Daina; Badsha, Humeira; Baecklund, Eva; Belmonte, Miguel; Craig-Müller, Jürgen; da Mota, Licia Maria Henrique; Dimic, Alexander; Fathi, Nihal A; Ferraccioli, Gianfranco; Fukuda, Wataru; Géher, Pál; Gogus, Feride; Hajjaj-Hassouni, Najia; Hamoud, Hisham; Haugeberg, Glenn; Henrohn, Dan; Horslev-Petersen, Kim; Ionescu, Ruxandra; Karateew, Dmitry; Kuuse, Reet; Laurindo, Ieda Maria Magalhaes; Lazovskis, Juris; Luukkainen, Reijo; Mofti, Ayman; Murphy, Eithne; Nakajima, Ayako; Oyoo, Omondi; Pandya, Sapan C; Pohl, Christof; Predeteanu, Denisa; Rexhepi, Mjellma; Rexhepi, Sylejman; Sharma, Banwari; Shono, Eisuke; Sibilia, Jean; Sierakowski, Stanislaw; Skopouli, Fotini N; Stropuviene, Sigita; Toloza, Sergio; Valter, Ivo; Woolf, Anthony; Yamanaka, Hisashi

2010-01-01

Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in

Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis.

PubMed

Ciurtin, Coziana; Wyszynski, Karol; Clarke, Robert; Mouyis, Maria; Manson, Jessica; Marra, Giampiero

2016-10-01

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation.

A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis.

PubMed

Chandran, Binu; Goel, Ajay

2012-11-01

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.

Cardiovascular safety of biologic therapies for the treatment of RA.

PubMed

Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

2011-11-15

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients.

PubMed

Lemmey, Andrew B; Wilkinson, Thomas J; Clayton, Rebecca J; Sheikh, Fazal; Whale, John; Jones, Hope S J; Ahmad, Yasmeen A; Chitale, Sarang; Jones, Jeremy G; Maddison, Peter J; O'Brien, Thomas D

2016-10-01

RA typically features rheumatoid cachexia [loss of muscle mass (MM) and excessive total fat mass (TFM), especially trunk FM], which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as treat-to-target (T2T), in attenuating inflammation would benefit body composition and physical function. This aim of this cross-sectional study was to assess the impact of T2T on body composition and objectively assessed function in RA patients. A total of 82 RA patients exclusively treated by T2T, were compared with 85 matched sedentary healthy controls (HCs). Body composition was estimated by DXA, with appendicular lean mass the surrogate measure of total MM. Physical function was assessed by knee extensor strength, handgrip strength, 30 s sit-to-stands, 8' up and go, and 50' walk (tests which reflect the ability to perform activities of daily living). Although generally well treated (mean DAS28 = 2.8, with 49% in remission), RA patients had ∼10% proportionally less appendicular lean mass and were considerably fatter (by ∼27%), particularly in the trunk (∼32%), than HCs. All measures of function were 24-34% poorer in the RA patients relative to HC. Despite marked improvements in disease control (most patients achieving or approaching remission), the relative loss of MM and increased adiposity in RA patients compared with matched HCs was similar to that observed pre-T2T. Additionally, performance of objective function tests was unchanged from that reported by our group for pre-T2T RA patients. Thus T2T, even in responsive RA patients, did not attenuate rheumatoid cachexia or improve objectively assessed function. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The induction of apoptosis by methotrexate in activated lymphocytes as indicated by fluorescence hyperpolarization: a possible model for predicting methotrexate therapy for rheumatoid arthritis patients.

PubMed

Herman, Shoshy; Zurgil, Naomi; Langevitz, Pnina; Ehrenfeld, Michael; Deutsch, Mordechai

2003-04-01

The objectives of this study were to test the in vitro response of healthy non-activated, activated, and rheumatoid arthritis (RA) lymphocytes to methotrexate (MTX), and design an in vitro model for predicting the efficiency of MTX treatment for RA patients. Considering the RA profile of clonal-expanded CD4(+) T cells, phytohemagglutinin-activated mononuclear cells taken from healthy donors were incubated with different concentrations of MTX. The MTX-immunosuppressive effect was tested by fluorescence intensity measurements, including PI assay and annexin V assay. For simple detection, we used the Individual Cell Scanner (IC-S), which enables the measurement of early events in individual cells. Healthy mononuclear cells (MNC), and MNC derived from RA patients, were tested by the IC-S while utilizing fluorescence polarization (FP) measurements of fluorescein diacetate (FDA) as an established marker of activation or suppression. In healthy activated MNC, we found that MTX, through its early incubation period, interferes with the activation signal obtained by PHA and exerts an apoptotic signal, which is noted by increases in the FP. Comparing our model to six long-standing RA patients and five newly-diagnosed patients revealed significant differences in the FP measurements, including fluorescence depolarization as an early established measurement of lymphocyte activation, and hyperpolarization as a measurement of an early immunosuppressive effect. We conclude that MTX, an effective therapy for RA patients, could easily be tested by fluorescence polarization measurements of FDA before (or during) clinical use in order to predict its efficiency on a specific RA patient. Moreover, the FP measurements can be used for the diagnosis, and making timing and dosage decisions.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab.

PubMed

Hattori, Yosuke; Kojima, Toshihisa; Kaneko, Atsushi; Kida, Daihei; Hirano, Yuji; Fujibayashi, Takayoshi; Yabe, Yuichiro; Oguchi, Takeshi; Kanayama, Yasuhide; Miyake, Hiroyuki; Kato, Takefumi; Takagi, Hideki; Hayashi, Masatoshi; Ito, Takayasu; Shioura, Tomone; Takahashi, Nobunori; Ishikawa, Hisato; Funahashi, Koji; Ishiguro, Naoki

2018-01-01

This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA). Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis. DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively. Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

Acne RA-1,2, a novel UV-selective face cream for patients with acne: Efficacy and tolerability results of a randomized, placebo-controlled clinical study.

PubMed

Cestone, Enza; Michelotti, Angela; Zanoletti, Valentina; Zanardi, Andrea; Mantegazza, Raffaella; Dossena, Maurizia

2017-06-01

General skincare measures such as the use of moisturisers and products containing adequate photoprotection are important components of acne patients' management to complement the pharmacological regimen. Acne RA-1,2 is a novel dermato-cosmetic product which contains selective photofilters and active ingredients against the multifactorial pathophysiology of acne. To evaluate the tolerability of Acne RA-1,2 and its effect on the clinical signs of acne. This double-blind, placebo-controlled study randomized 40 adult patients with 10-25 comedones per half face to once-daily application of Acne RA-1,2 or placebo for 8 weeks. Evaluations after 4 and 8 weeks included the number of comedones, transepidermal water loss (TEWL), sebum production, and tolerability. In the Acne RA-1,2 group, there was a significant 35% decrease in the mean number of comedones from 26 at baseline to 17 at Week 8 (P<.001), a 7% significant reduction in TEWL (9.32 to 8.66 g/h/m 2 ; P<.001), and a 24% significant reduction in sebum production (154.8 to 117.6 μg/cm 2 ; P<.001). The reductions in TEWL and sebum production were significantly greater than those in the placebo group at Weeks 4 and 8 (P<0.05). There were no adverse events. Acne RA-1,2 was well tolerated and effective at reducing comedones and sebum production and improving epidermal barrier function. These results suggest that Acne RA-1,2 is useful against acne-prone facial skin, particularly as it targets sebum production, which topical pharmacological acne therapies do not address. © 2017 Wiley Periodicals, Inc.

Detection and quantification of 223Ra uptake in bone metastases of patients with castration resistant prostate carcinoma, with the aim of determining the absorbed dose in the metastases.

PubMed

Mínguez, P; Gómez de Iturriaga, A; Fernández, I L; Rodeño, E

To obtain the necessary acquisition and calibration parameters in order to evaluate the possibility of detecting and quantifying 223 Ra uptake in bone metastases of patients treated for castration resistant prostate carcinoma. Furthermore, in the cases in which the activity can be quantified, to determine the absorbed dose. Acquisitions from a Petri dish filled with 223 Ra were performed in the gamma camera. Monte Carlo simulations were also performed to study the partial volume effect. Formulae to obtain the detection and quantification limits of 223 Ra uptake were applied to planar images of two patients 7 days post-administration of 55kBq/kg of 223 Ra. In order to locate the lesions in advance, whole-body scans and SPECT/CT images were acquired after injecting 99m Tc-HDP. The optimal energy window was found to be at 82keV with a medium-energy collimator MEGP. Of the lesions found in the patients, only those that had been detected in both the AP and PA projections could be quantified. These lesions were those which had shown a higher 99m Tc-HDP uptake. The estimated values of absorbed doses ranged between 0.7Gy and 7.8Gy. Of the lesions that can be detected, it is not possible to quantify the activity uptake in some of them, which means that the absorbed dose cannot be determined either. This does not mean that the absorbed dose in these lesions can be regarded as negligible. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

PubMed Central

2010-01-01

Introduction Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant

Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study

PubMed Central

Jacquemin, Charlotte; Molto, Anna; Servy, Hervé; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Granger, Benjamin; Fautrel, Bruno; Gossec, Laure

2017-01-01

Background The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. Methods This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. Results In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%–21% and an absolute decrease ranging from 836 to 1462 steps/day. Conclusion Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares. PMID:28879046

Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA): a case report with literature review.

PubMed

Inoue, M; Yanaihara, N; Okamoto, A

2014-01-01

Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA) is reported here. A 33-year-old nulliparous woman with a 16-year history of RA who had been treated with corticosteroid and immunosuppressive drugs was diagnosed as having a non-typhoidal Salmonella ovarian abscess which might have been preceded by an occurrence of endometriotic cyst. Multidisciplinary therapy including surgical intervention was required to complete the eradication of infection. Although Salmonella ovarian abscess is rare, it may cause a serious complication in the ovary harboring endometriotic cyst through sustained presence of Salmonella bacteraemia.

The burden of the 'RA RA' positive: survivors' and hospice patients' reflections on maintaining a positive attitude to serious illness.

PubMed

McGrath, Pam

2004-01-01

This article seeks to make a contribution to fostering work on the neglected area of research about how individuals maintain a positive outlook during their confrontation with serious illness. Insights are presented from both haematology survivors and hospice patients about the factors that hinder and facilitate their capacity to 'be positive'. Open-ended interviews with 14 hospice patients and 12 haematology survivors on their construction of meaning in the face of serious illness were audio-recorded, transcribed verbatim and thematically analysed. The findings on the topic of maintaining a positive outlook are presented in this article. Although the participants affirmed the value of a positive perspective on their illness experience, they were critical of unwanted pressure from others to be positive: a phenomenon they called the 'RA RA' positive. Such pressure interfered with the natural process of continually having to re-negotiate a positive outlook through exploring the fullness of feeling, both positive and negative. The participants indicated that at times of relapse or worsening physical condition they had to cycle through a process of despair/negativity and re-adjustment before they were able to find the positive. The process could not be rushed and required freedom from an imposed pressure to be positive. The essential message is that a positive outlook cannot be imposed but requires a nurturing orientation that allows the expression of a full range of feelings in a supportive environment.

[Secondary amyloidosis in patients with rheumatoid arthritis(RA)].

PubMed

Inada, Shinichi

2002-12-01

The amyloidoses are a group of protein deposition diseases in which amyloid proteins composed of insoluble fibrils are deposited in various organs. Most cases of the secondary amyloidosis(AA amyloidosis) in which amyloid A(AA) protein is deposited followed by uncontrolled, long term RA(duration 7 to 10 years). It has been revealed that the multi-organ dysfunction associated with AA amyloidosis causes the deterioration of RA prognosis. Since the mechanism of amyloid protein deposition is still unknown, the diagnosis of AA amyloidosis is difficult and there is no fundamental therapy for it; there are only supportive therapies for the malfunction of involved organs.

Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

PubMed

Harris, Nathaniel; Eudy, Amanda; Clowse, Megan

2018-06-15

While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this activity is typically assessed by the physician. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. Univariate and multivariable regression models were used to assess the relationship between patient and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with lupus or rheumatoid arthritis (RA) enrolled in a prospective registry at a single academic center from 2008-2016. In women with RA, patient-reported disease activity is associated with preterm birth (OR 5.9 (1.5-23.9)), and gestational age (beta -1.5 weeks (-2.6, -0.4 weeks)). The physician assessment of disease activity also predicted preterm (OR 2.1 (1.2-3.5)), small for gestational age births (OR 1.8 (1.03-3.1), and gestational age in weeks (beta -0.6 weeks (-0.9, -0.02 weeks)). On the other hand, SLE patient-reported disease activity measures, including the HAQ, pain or global health measures, are not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 (1.-6.3)), cesarean delivery (OR 2.3 (1.0-5.3)), and preeclampsia (OR 2.8 (1.3-6.3)). The results do not appear to be driven by lupus nephritis or antiphospholipid syndrome. For women with RA, patient-reported measures of disease activity may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, no patient-reported measures were associated with adverse outcomes while physician measures of disease activity helped predict several adverse pregnancy outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study.

PubMed

Peterfy, Charles; Emery, Paul; Tak, Paul P; Østergaard, Mikkel; DiCarlo, Julie; Otsa, Kati; Navarro Sarabia, Federico; Pavelka, Karel; Bagnard, Marie-Agnes; Gylvin, Lykke Hinsch; Bernasconi, Corrado; Gabriele, Annarita

2016-01-01

To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. NCT00578305. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Process evaluation of the RaDIANT community study: a dialysis facility-level intervention to increase referral for kidney transplantation.

PubMed

Hamoda, Reem E; Gander, Jennifer C; McPherson, Laura J; Arriola, Kimberly J; Cobb, Loren; Pastan, Stephen O; Plantinga, Laura; Browne, Teri; Hartmann, Erica; Mulloy, Laura; Zayas, Carlos; Krisher, Jenna; Patzer, Rachel E

2018-01-15

The Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT) was an End-Stage Renal Disease (ESRD) Network 6-developed, dialysis facility-level randomized trial testing the effectiveness of a 1-year multicomponent education and quality improvement intervention in increasing referral for kidney transplant evaluation among selected Georgia dialysis facilities. To assess implementation of the RaDIANT intervention, we conducted a process evaluation at the conclusion of the intervention period (January-December 2014). We administered a 20-item survey to the staff involved with transplant education in 67 dialysis facilities randomized to participate in intervention activities. Survey items assessed facility participation in the intervention (fidelity and reach), helpfulness and willingness to continue intervention activities (sustainability), suggestions for improving intervention components (sustainability), and factors that may have influenced participation and study outcomes (context). We defined high fidelity to the intervention as completing 11 or more activities, and high participation in an activity as having at least 75% participation across intervention facilities. Staff from 65 of the 67 dialysis facilities completed the questionnaire, and more than half (50.8%) reported high adherence (fidelity) to RaDIANT intervention requirements. Nearly two-thirds (63.1%) of facilities reported that RaDIANT intervention activities were helpful or very helpful, with 90.8% of facilities willing to continue at least one intervention component beyond the study period. Intervention components with high participation emphasized staff and patient-level education, including in-service staff orientations, patient and family education programs, and patient educational materials. Suggested improvements for intervention activities emphasized addressing financial barriers to transplantation, with financial education materials perceived as most helpful among Ra

SU-F-J-08: Quantitative SPECT Imaging of Ra-223 in a Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue, J; Hobbs, R; Sgouros, G

Purpose: Ra-223 therapy of prostate cancer bone metastases is being used to treat patients routinely. However, the absorbed dose distribution at the macroscopic and microscopic scales remains elusive, due to the inability to image the small activities injected. Accurate activity quantification through imaging is essential to calculate the absorbed dose in organs and sub-units in radiopharmaceutical therapy, enabling personalized absorbed dose-based treatment planning methodologies and more effective and optimal treatments. Methods: A 22 cm diameter by 20 cm long cylindrical phantom, containing a 3.52 cm diameter sphere, was used. A total of 2.01 MBq of Ra-223 was placed in themore » phantom with 177.6 kBq in the sphere. Images were acquired on a dual-head Siemens Symbia T16 gamma camera using three 20% full-width energy windows and centered at 84, 154, and 269 keV (120 projections, 360° rotation, 45 s per view). We have implemented reconstruction of Ra-223 SPECT projections using OS-EM (up to 20 iterations of 10 subsets) with compensation for attenuation using CT-based attenuation maps, collimator-detector response (CDR) (including septal penetration, scatter and Pb x-ray modeling), and scatter in the patient using the effective source scatter estimation (ESSE) method. The CDR functions and scatter kernels required for ESSE were computed using the SIMIND MC simulation code. All Ra-223 photon emissions as well as gamma rays from the daughters Rn-219 and Bi-211 were modeled. Results: The sensitivity of the camera in the three combined windows was 107.3 cps/MBq. The visual quality of the SPECT images was reasonably good and the activity in the sphere was 27% smaller than the true activity. This underestimation is likely due to partial volume effect. Conclusion: Absolute quantitative Ra-223 SPECT imaging is achievable with careful attention to compensate for image degrading factors and system calibration.« less

High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints.

PubMed Central

Gerli, R; Muscat, C; Bistoni, O; Falini, B; Tomassini, C; Agea, E; Tognellini, R; Biagini, P; Bertotto, A

1995-01-01

The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA. PMID:8536371

The activity ratio of 228Th to 228Ra in bone tissue of recently deceased humans: a new dating method in forensic examinations.

PubMed

Zinka, Bettina; Kandlbinder, Robert; Schupfner, Robert; Haas, Gerald; Wolfbeis, Otto S; Graw, Matthias

2012-01-01

Reliable determination of time since death in human skeletons or single bones often is limited by methodically difficulties. Determination of the specific activity ratio of natural radionuclides, in particular of 232Th (Thorium), 228Th and 228Ra (Radium) seems to be a new appropriate method to calculate the post mortem interval. These radionuclides are incorporated by any human being, mainly from food. So with an individual's death the uptake of radionuclides ends. But the decay of 232Th produces 228Ra and 228Th due to its decay series, whereas 228Th is continuously built up in the human's bones. Thus, it can be concluded that in all deceased humans at different times after death different activity ratios of 228Th to 228Ra will develop in bone. According to this fact it should be possible to calculate time since death of an individual by first analysing the specific activities of 228Th and 228Ra in bones of deceased and then determining the 228Th/228Ra activity ratio, which can be assigned to a certain post-mortem interval.

Measuring 226Ra/228Ra in Oceanic Lavas by MC-ICPMS

NASA Astrophysics Data System (ADS)

Standish, J. J.; Sims, K.; Ball, L.; Blusztajn, J.

2007-12-01

238U-230Th-226Ra disequilibrium in volcanic rocks provides an important and unique tool to evaluate timescales of recent magmatic processes. Determination of 230Th-226Ra disequilibria requires measurement of U and Th isotopes and concentrations as well as measurement of 226Ra. While measurement of U and Th by ICPMS is now well established, few published studies documenting 226Ra measurement via ICPMS exist. Using 228Ra as an isotope spike we have investigated two ion-counting methods; a 'peak-hopping' routine, where 226Ra and 228Ra are measured in sequence on the central discrete dynode ETP secondary electron multiplier (SEM), and simultaneous measurement of 226Ra and 228Ra on two multiple ion-counter system (MICS) channeltron type detectors mounted on the low end of the collector block. Here we present 226Ra measurement by isotope dilution using the Thermo Fisher NEPTUNE MC-ICPMS. Analysis of external rock standards TML and AThO along with mid-ocean ridge basalt (MORB) and ocean island basalt (OIB) samples show three issues that need to be considered when making precise and accurate Ra measurements: 1) mass bias, 2) background, and 3) relative efficiencies of the detectors when measuring in MICS mode. Due to the absence of an established 226Ra/228Ra standard, we have used U reference material NBL-112A to monitor mass bias. Although Ball et. al., (in press) have shown that U does not serve as an adequate proxy for Th (and thus not likely for Ra either), measurements of rock standards TML and AThO are repeatedly in equilibrium within the uncertainty of the measurements (where total uncertainty includes propagation of the uncertainty in the 226Ra standard used for calibrating the 228Ra spike). For this application, U is an adequate proxy for Ra mass bias at the 1% uncertainly level. The more important issue is the background correction. Because of the extensive chemistry required to separate and purify Ra (typically fg/g level in volcanic rocks), we observe large

Differential Expression of NK Receptors CD94 and NKG2A by T Cells in Rheumatoid Arthritis Patients in Remission Compared to Active Disease

PubMed Central

Walsh, Ceara E.; Ryan, Elizabeth J.; O’Farrelly, Cliona; Golden-Mason, Lucy; FitzGerald, Oliver; Veale, Douglas J.; Bresnihan, Barry; Fearon, Ursula

2011-01-01

Objective TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal. Methods Patients with RA were recruited for this study, (i) RA patients in clinical remission following a minimum of one year of TNFi therapy (n = −15); (2) Active RA patients, not currently or ever receiving TNFi (n = 18); and healthy control volunteers (n = 15). Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b) expression on T-(CD3+CD56−), NK-(CD3−CD56+) and NKT-(CD3+CD56+) cells was determined by flow cytometry. Results Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05). CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05), with no differences observed for CD161 and CD57. CD3+CD56− cell expression of NKG2A was inversely related to DAS28 (r = −0.612, p<0.005). Conclusion High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA

Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.

PubMed

Walsh, Ceara E; Ryan, Elizabeth J; O'Farrelly, Cliona; Golden-Mason, Lucy; FitzGerald, Oliver; Veale, Douglas J; Bresnihan, Barry; Fearon, Ursula

2011-01-01

TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal. Patients with RA were recruited for this study, (i) RA patients in clinical remission following a minimum of one year of TNFi therapy (n = -15); (2) Active RA patients, not currently or ever receiving TNFi (n = 18); and healthy control volunteers (n = 15). Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b) expression on T-(CD3+CD56-), NK-(CD3-CD56+) and NKT-(CD3+CD56+) cells was determined by flow cytometry. Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3+CD56-T cells from patients in remission compared to active RA (p<0.05). CD3+CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p<0.05), with no differences observed for CD161 and CD57. CD3+CD56- cell expression of NKG2A was inversely related to DAS28 (r = -0.612, p<0.005). High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study.

PubMed

Arts, Elke; Fransen, Jaap; Lemmers, Heidi; Stalenhoef, Anton; Joosten, Leo; van Riel, Piet; Popa, Calin D

2012-05-14

Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity. Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol. HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186). Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment.

PubMed

Taylor, Peter C; Alten, Rieke; Gomez-Reino, Juan J; Caporali, Roberto; Bertin, Philippe; Sullivan, Emma; Wood, Robert; Piercy, James; Vasilescu, Radu; Spurden, Dean; Alvir, Jose; Tarallo, Miriam

2018-01-01

Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.

What RA patients expect of their treatment--discussion over the result of our survey.

PubMed

Funahashi, Keiko; Matsubara, Tsukasa

2012-11-01

We conducted a survey among Japanese rheumatoid arthritis (RA) patients to better understand what they expect from treatment and whether there is a difference between expectations of biologics-treated and disease-modifying antirheumatic drugs (DMARDs)-treated patients. An anonymous survey was conducted with 165 outpatients from our clinic (with informed written consent). On the survey, they wrote their age, gender, medical history, and commented on: (1) expectations for treatment, (2) disappointment with treatment, (3) experience of, and thoughts about switching treatments, (4) information wanted before starting a new treatment, (5) expectations before administration and noticeable differences after treatment, (6) level of satisfaction with current treatment, and (7) expectations of possible treatments. Patients who had never been treated with DMARDs were excluded from the survey. For "treatment goals before administration," 86 % responded with "assured efficacy," while 73 % responded "suppress joint destruction" or "recover from joint destruction." Also, more patients hoped for "long-lasting efficacy" (67 %) over "fast acting" (41 %), which suggests significance of the long-term improvement of QOL. Related to "disappointment with treatment," patients also felt anxiety over switching treatment for possibilities of not responding enough, or side effects. RA patients have high expectations for medication in terms of assured improvement of conditions and long-lasting efficacy of drugs, while the biggest concern was if they would have side effects or not, and if so, what type. The results suggest patients hope to have worries over switching medications dispelled. The results also verified those who have used biologics before have higher treatment goals than those who have not.

Engagement and satisfaction with an Internet-based physical activity intervention in patients with rheumatoid arthritis.

PubMed

van den Berg, M H; Ronday, H K; Peeters, A J; Voogt-van der Harst, E M; Munneke, M; Breedveld, F C; Vliet Vlieland, T P M

2007-03-01

To assess the engagement in and satisfaction with an Internet-mediated physical activity intervention with individual supervision in patients with rheumatoid arthritis (RA). The intervention studied was one of the two strategies aimed at enhancing physical activity in RA patients that were being compared in a randomized controlled trial. A total of 82 patients, all experienced in using Internet and e-mail and registered at three different rheumatology out-patient clinics, were randomly allocated to the Internet-mediated individualized intervention (52 weeks). They had access to personal physical activity schedules and received individual supervision by a physical therapist by means of weekly e-mail feedback. In addition, telephone contacts, an online discussion forum, six face-to-face group meetings and electronic newsletters were offered. Besides registration of returned physical activity schedules, engagement and satisfaction were measured through questionnaires. The median physical activity schedule return rate of the 82 participants was 55%. The mean number of patients logging into the website at least once a week was 53 (70%) over 12 months. Of all patients, 69 returned the questionnaires (response 84%). Telephone contacts were used by 38/67 patients (57%), the mean (SD) number of attended group meetings was 3.1 (1.5) and the discussion forum comprised 15 posted messages. Overall, the proportions of patients being (very) satisfied with the amount of e-mail contacts, telephone contacts, usefulness of website information, physical activity schedules, group meetings and website layout were >/=85%. A smaller proportion of patients were satisfied with the links to other websites (68%), the newsletters (55%) and the online discussion forum (32%). Physical activity schedules with weekly feedback by e-mail, telephone contacts and a limited number of group meetings were frequently used website tools and modes of communication of an Internet-based physical activity

Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy.

PubMed

Ostrowski, Sisse R; Katzenstein, Terese L; Thim, Per T; Pedersen, Bente K; Gerstoft, Jan; Ullum, Henrik

2005-02-01

Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels patients had HIV RNA levels patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05). These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.

Criterion validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF) for use in patients with rheumatoid arthritis: comparison with the SenseWear Armband.

PubMed

Tierney, M; Fraser, A; Kennedy, N

2015-06-01

The International Physical Activity Questionnaire Short Form (IPAQ-SF) is a self-report questionnaire commonly used in patients with rheumatoid arthritis (RA) to measure physical activity. However, despite its frequent use in patients with RA, its validity has not been ascertained in this population. The aim of this study was to examine the criterion validity of energy expenditure from physical activity recorded with the IPAQ-SF in patients with RA compared with the objective criterion measure, the SenseWear Armband (SWA) which has been validated previously in this population. Cross-sectional criterion validation study. Regional hospital outpatient setting. Twenty-two patients with RA attending outpatient rheumatology clinics. Subjects wore an SWA for 7 full consecutive days and completed the IPAQ-SF. Energy expenditure from physical activity recorded by the SWA and the IPAQ-SF. Energy expenditure from physical activity recorded by the IPAQ-SF and the SWA showed a small, non-significant correlation (r=0.407, P=0.60). The IPAQ-SF underestimated energy expenditure from physical activity by 41% compared with the SWA. This was corroborated using Bland and Altman plots, as the IPAQ-SF was found to overestimate energy expenditure from physical activity in nine of the 22 individuals, and underestimate energy expenditure from physical activity in the remaining 13 individuals. The IPAQ-SF has limited use as an accurate and absolute measure for estimating energy expenditure from physical activity in patients with RA. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Regional differences in baseline disease activity and remission rates following golimumab treatment for RA: results from the GO-MORE trial.

PubMed

Durez, Patrick; Pavelka, Karel; Lazaro, Maria Alicia; Garcia-Kutzbach, Abraham; Moots, Robert J; Amital, Howard; Govoni, Marinella; Vastesaeger, Nathan

2018-05-01

GO-MORE (NCT00975130) was a large open-label, multinational, multicenter, prospective phase 3 trial evaluating add-on therapy with golimumab in biologic-naïve patients with active rheumatoid arthritis (RA). The objective of this post hoc analysis was to examine regional differences in baseline disease activity and remission rates following golimumab treatment for RA. This was a planned, descriptive post hoc analysis of data from the GO-MORE trial. Baseline disease activity and remission were defined as moderate or severe based on EULAR criteria. This analysis included 3280 participants from the GO-MORE trial. All participants included in this analysis had high or moderate disease activity at baseline. At baseline, high disease activity was least common in Europe (71.0%), Canada (77.0%), and the Middle East (78.2%) and most common in Latin America (90.7%), South Africa (91.5%), and Asia (92.5%). Month 6 remission rates were highest in South Africa (29.1%), Europe (27.9%), and the Middle East (27.3%) and lowest in Canada (19.7%), Latin America (17.2%), and Asia (15.0%). Higher rates of remission in each geographical region generally corresponded with lower baseline disease activity. We suspect that access to care and implementation of the treat-to-target strategy were the most important determinants, but this apparent relationship needs to be confirmed in further studies that include a statistical analysis of prognostic indicators.

Disease activity, knee function, and walking ability in patients with rheumatoid arthritis 10 years after primary total knee arthroplasty.

PubMed

Nishikawa, Masataka; Owaki, Hajime; Takahi, Koichiro; Fuji, Takeshi

2014-04-01

To evaluate disease activity, knee function, and walking ability of patients with rheumatoid arthritis (RA) over 10 years after total knee arthroplasty (TKA). Four men and 26 women (mean age, 59.9 years) underwent 42 TKAs for RA with a mean duration of 151.3 months and were followed up for a mean of 142.3 months. Preoperatively, disease activity was assessed by C-reactive protein (CRP) level only, and the range of knee motion was recorded. At the final follow-up, tender joint count, swollen joint count, visual analogue scale of RA symptoms, and the Modified Health Assessment Questionnaire (MHAQ) score were assessed. Disease activity was evaluated using CRP, matrix metalloproteinase-3, and Disease Activity Score. Range of motion and Knee Society knee and function scores were also assessed. The use of methotrexate increased from 4 patients preoperatively to 20 patients at the final follow-up (p<0.001), and the mean dose increased from 3.9 to 6.3 mg/week (p<0.001). Among the 30 patients, the mean CRP level decreased from 2.63 mg/dl preoperatively to 0.61 mg/dl at the final follow-up (p<0.001). Disease activity was controlled. At the final follow-up, disease activity was in remission in 10 patients, low in 11, and moderate in 9. The mean Knee Society knee score was excellent (91.0), but the mean function score was poor (57.0) and diverse. Severe walking disability (function score, <40) was noted in 8 patients (11 TKAs). Knee and function scores did not correlate. Walking ability in patients with RA after TKA was generally poor. Poor function was associated with a history of spinal or lower extremity fracture surgery and the MHAQ score.

Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity.

PubMed

Inciarte-Mundo, José; Ramirez, Julio; Hernández, Maria Victoria; Ruiz-Esquide, Virginia; Cuervo, Andrea; Cabrera-Villalba, Sonia Raquel; Pascal, Mariona; Yagüe, Jordi; Cañete, Juan D; Sanmarti, Raimon

2016-07-08

Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 μg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0

Organizing Pneumonia in Rheumatoid Arthritis Patients: A Case-Based Review

PubMed Central

Mori, Shunsuke; Koga, Yukinori; Sugimoto, Mineharu

2015-01-01

We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA-associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients. PMID:26543387

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

PubMed

Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Impact of etanercept on work and activity impairment in employed moderate to severe rheumatoid arthritis patients in the United States.

PubMed

Hone, Devon; Cheng, Annie; Watson, Crystal; Huang, Baisong; Bitman, Bojena; Huang, Xing-Yue; Gandra, Shravanthi R

2013-10-01

To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA). This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test. RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001). In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment. Copyright © 2013 by the American College of Rheumatology.

ACPA-Negative RA Consists of Two Genetically Distinct Subsets Based on RF Positivity in Japanese

PubMed Central

Terao, Chikashi; Ohmura, Koichiro; Ikari, Katsunori; Kochi, Yuta; Maruya, Etsuko; Katayama, Masaki; Yurugi, Kimiko; Shimada, Kota; Murasawa, Akira; Honjo, Shigeru; Takasugi, Kiyoshi; Matsuo, Keitaro; Tajima, Kazuo; Suzuki, Akari; Yamamoto, Kazuhiko; Momohara, Shigeki; Yamanaka, Hisashi; Yamada, Ryo; Saji, Hiroo; Matsuda, Fumihiko; Mimori, Tsuneyo

2012-01-01

HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10−6 and 0.0011, OR: 1.57 (1.28–1.91) and 1.37 (1.13–1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21–1.89) and 3.08 (1.68–5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote. PMID:22792215

Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity

PubMed Central

Toussirot, Éric; Saas, Philippe; Deschamps, Marina; Pouthier, Fabienne; Perrot, Lucille; Perruche, Sylvain; Chabod, Jacqueline; Tiberghien, Pierre; Wendling, Daniel

2009-01-01

Introduction Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied. Methods Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR). Results High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL. Conclusions SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA. PMID:19570209

Niclosamide as an adjuvant to etanercept in treatment patients with active rheumatoid arthritis: an 8-week randomized controlled pilot study.

PubMed

Al-Gareeb, Ali Ismail A; Gorial, Faiq Isho; Mahmood, Ahmed S

2018-06-07

This study designed to identify the therapeutic efficacy of niclosamide (NCL) in Iraqi patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA. One hundred ten patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA were allocated randomly into two equal groups: one of them treated with 1000 mg/day NCL and the other treated with 1000 mg/day lactose in capsule dosage form. The study duration was 8 weeks. Clinical efficacy of the NCL was measured depending on scoring of the 28-joint Disease Activity Score (DAS28), simple disease activity index (SDAI), clinical disease activity index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) at the baseline and at the end of the 8-week treatment period. Moreover, blood sample were taken from the patients at baseline and at after 8 weeks of treatment for measurement of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin 1β (IL-1 β), interleukin-6, tumor necrosis factor (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. At the end of the clinical study, patients had good response to NCL when added to the ETN with a high significant improvement in the SJC, TJC, DAS-28, CDAI, SDAI, and HAQ-DI compared to patients who were received placebo drug. In addition to that, 33% of patients achieved an ACR 20% response (ACR20) on NCL and ETN. Of these, 4% achieved ACR50 and another 4% achieved ACR70 response. While those group treated by placebo + ETN, 5% achieved ACR20 response and no one reached to ACR50 or ACR70 response. Twenty-seven percent of RA patients who have taken the NCL achieved moderate EULAR score while only 17% from the group that taken placebo with ETN achieved moderate response. On the other hand, no significant

[Effects of low-intensity infrared impulse laser therapy on inflammation activity markers in patients with rheumatoid arthritis].

PubMed

Ilich-Stoianovich, O; Nasonov, E L; Balabanova, R M

2000-01-01

To evaluate effects of low-intensity infrared impulse laser therapy (IRILT) on concentration of immunity activation [not readable: see text] (soluble receptors of TNF-alpha and neopterin) and indicator of the inflammation activity (concentration of C-reactive protein) in patients with rheumatoid arthritis (RA). Enzyme immunoassay, radioimmunoassay, enzyme immunoassay and radial immunodiffusion were used to measure soluble receptors of TNF-alpha, neopterin and C-reactive protein in 38 females with verified RA receiving IRILT or sham procedures. IRILT induced lowering of neopterin, TNF-alpha soluble receptors (p < 0.01) and C-reactive protein (p < 0.01). The findings give pathogenetical grounds for IRILT use in RA as this treatment suppresses functional activity of macrophages which serve the main source of neopterin and the receptors synthesis.

Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.

PubMed

van Rensburg, Ilana C; Wagman, Chandre; Stanley, Kim; Beltran, Caroline; Ronacher, Katharina; Walzl, Gerhard; Loxton, Andre G

2017-01-10

Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.

Patient-centred care in established rheumatoid arthritis.

PubMed

Voshaar, M J H; Nota, I; van de Laar, M A F J; van den Bemt, B J F

2015-01-01

Review of the evidence on patient-centred care (PCC) in rheumatoid arthritis (RA) shows that involving the patient as an individual - with unique needs, concerns and preferences - has a relevant impact on treatment outcomes (safety, effectiveness and costs). This approach empowers patients to take personal responsibility for their treatment. Because clinicians are only able to interact personally with their patients just a few hours per year, patients with a chronic condition such as RA should be actively involved in the management of their disease. To stimulate this active role, five different PCC activities can be distinguished: (1) patient education, (2) patient involvement/shared decision-making, (3) patient empowerment/self-management, (4) involvement of family and friends and (5) physical and emotional support. This article reviews the existing knowledge on these five PCC activities in the context of established RA management, especially focused on opportunities to increase medication adherence in established RA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative analysis of disease activity measures, use of biologic agents, body mass index, radiographic features, and bone density in psoriatic arthritis and rheumatoid arthritis patients followed in a large U.S. disease registry.

PubMed

Reddy, Soumya M; Anandarajah, Allen P; Fisher, Mark C; Mease, Philip J; Greenberg, Jeffrey D; Kremer, Joel M; Reed, George; Chen, Rui; Messing, Susan; Kaukeinen, Kimberly; Ritchlin, Christopher T

2010-12-01

To compare disease activity, radiographic features, and bone density in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) matched cohorts. Disease activity and radiographic data in the Consortium of Rheumatology Researchers of North America database from 2001 to 2008 were compared for 2481 patients with PsA and 17,107 patients with RA subsequently matched for age, gender, and disease duration. Radiographic outcomes included presence of erosions, and joint deformity. In addition, bone mineral density (BMD) scores for lumbar spine (L-spine) and femoral neck were compared using the same matching criteria plus weight and smoking status. Tender (4.5 vs 3.4, p < 0.001) and swollen (4.4 vs 2.9, p < 0.012) joint counts, and modified Health Assessment Questionnaire scores were significantly higher (0.4 vs 0.3, p < 0.001) in patients with RA compared with patients with PsA. Patient general health and pain scores were also higher in patients with RA vs patients with PsA. Joint erosions (47.4% vs 37.6%, p = 0.020) and deformity (25.2% vs 21.6%, p = 0.021) were more prevalent in RA than PsA. In multivariate analysis, a reduced prevalence of erosions in PsA vs RA was noted (OR 0.609, p < 0.001). After matching, T-scores for L-spine (-0.54 vs -0.36, p = 0.077) and femoral neck (-0.88 vs -0.93, p = 0.643) were similar in patients with RA and patients with PsA, although body weight was a major confounder. The level of disease activity and radiographic damage was significantly higher for RA vs PsA subjects, although the magnitude of differences was relatively small. BMD levels were comparable between cohorts. Outcomes in patients with PsA and patients with RA may be more similar than previously reported.

Pain intensity and abdominal muscle activation during walking in patients with low back pain: The STROBE study.

PubMed

Kim, Si-Hyun; Park, Kyue-Nam; Kwon, Oh-Yun

2017-10-01

Nonspecific low back pain (LBP) is a common musculoskeletal problem that is intensified during physical activity. Patients with LBP have been reported to change their abdominal muscle activity during walking; however, the effects of pain intensity, disability level, and fear-avoidance belief on this relationship have not been evaluated. Thus, we compared abdominal muscle activity in patients with LBP and asymptomatic controls, and assessed the impact of pain intensity, disability level, and fear-avoidance belief.Thirty patients with LBP divided into groups reporting low (LLBP) and high-pain intensity low back pain (HLBP), and 15 participants without LBP were recruited. LBP patients' self-reported pain intensity, disability, and fear-avoidance belief were recorded. To examine abdominal muscle activity (rectus abdominis [RA], internal [IO], and external oblique [EO] muscles) during walking, all subjects walked at a self-selected speed. Abdominal muscle activity (RA, IO, and EO) was compared among groups (LLBP, HLBP, and controls) in different phases of walking (double support vs swing). Relationships between abdominal muscle activity and clinical measures (pain intensity, disability, fear-avoidance belief) were analyzed using partial correlation analysis.Right IO muscle activity during walking was significantly decreased in LLBP and HLBP compared with controls in certain walking phase. Partial correlation coefficients showed significant correlations between fear-avoidance belief and right EO activity (r = .377, P < .05) and between disability index and left IO activity (r = .377, P < .05) in patients with LBP. No significant difference was found in abdominal muscle activity in walking between patients with LLBP and HLBP (P > .05).This study demonstrated decreased IO muscle activity during certain walking phases in LLBP and HLBP compared with asymptomatic participants. Although altered IO muscle activity during walking was observed in patients with

Effect of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor on Disease Activity in Patients With Rheumatoid Arthritis

PubMed Central

Xing, Bin; Yin, Yu-Feng; Zhao, Li-Dan; Wang, Li; Zheng, Wen-Jie; Chen, Hua; Wu, Qing-Jun; Tang, Fu-Lin; Zhang, Feng-Chun; Shan, Guangliang; Zhang, Xuan

2015-01-01

Abstract HMG-CoA reductase inhibitors (also known as statins) are widely used as lipid-lowering agents in patients with rheumatoid arthritis (RA) to reduce their cardiovascular risk. However, whether they have an effect on RA disease activity is controversial. This study aimed to investigate the effect of statins on disease activity in RA patients. A systematic literature review was performed using the MEDLINE, EMBASE, Cochrane Library, ISI WEB of Knowledge, Scopus, and Clinical Trials Register databases. Only prospective randomized controlled trials or controlled clinical trials comparing the efficacy of statins with placebo on adult RA patients were included. The efficacy was measured according to the ACR criteria, EULAR criteria, DAS28, HAQ score, ESR, or CRP. The Jadad score was used for quality assessment. The inverse variance method was used to analyze continuous outcomes. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis. Publication bias was assessed using Egger test. A total 13 studies involving 737 patients were included in the meta-analysis; 11 studies were included in the meta-analysis based on DAS28, while the other 2 studies were only included in the meta-analysis based on ESR or CRP. The standardized mean difference (SMD) in DAS28 between the statin group and the placebo group was −0.55 (95% CI [−0.83, −0.26], P = 0.0002), with an I2 value of 68%. Subgroup analysis showed that patients with more active disease tended to benefit more from statin therapy (SMD −0.73, P = 0.01) than patients with moderate or low disease activity (SMD −0.38, P = 0.03). Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not

SoRa first flight. Summer 2009

NASA Astrophysics Data System (ADS)

Pirrotta, S.; Flamini, E.

The SoRa (Sounding Radar) experiment was successfully launched from Longyearbyen (Svalbard, Norway) during the summer 2009 campaign managed by the Italian/Norwegian "Nobile Amundsen / Stratospheric Balloon Centre" (NA/SBC). SoRa is part of the Italian Space Agency (ASI) programs for Long Duration Balloon Flights. Carried by the biggest balloon (800.000 m3) ever launched in polar regions, SoRa main experiment and its three piggyback payloads (DUSTER, ISA and SIDERALE) performed a nominal flight of almost 4 days over the North Sea and Greenland, until the separation, landing and recovery in Baffin Island (Canada). Despite the final destructive event that compromise the scientific main goal of SoRa, the 2009 ASI balloon campaign can be considered an important milestone, because of the obtained scientific and technical results but also for the lesson learned by the science, engineering and managerial teams looking at the future ASI scientific balloon-born activities.

Association of weight loss with improved disease activity in patients with rheumatoid arthritis: A retrospective analysis using electronic medical record data

PubMed Central

Kreps, David J.; Halperin, Florencia; Desai, Sonali P.; Zhang, Zhi Z.; Losina, Elena; Olson, Amber T.; Karlson, Elizabeth W.; Bermas, Bonnie L.; Sparks, Jeffrey A.

2018-01-01

Objective To evaluate the association between weight loss and rheumatoid arthritis (RA) disease activity. Methods We conducted a retrospective cohort study of RA patients seen at routine clinic visits at an academic medical center, 2012–2015. We included patients who had ≥2 clinical disease activity index (CDAI) measures. We identified visits during follow-up where the maximum and minimum weights occurred and defined weight change and CDAI change as the differences of these measures at these visits. We defined disease activity improvement as CDAI decrease of ≥5 and clinically relevant weight loss as ≥5 kg. We performed logistic regression analyses to establish the association between improved disease activity and weight loss and baseline BMI category (≥25 kg/m2 or <25 kg/m2). We built linear regression models to investigate the association between continuous weight loss and CDAI change among patients who were overweight/obese at baseline and who lost weight during follow-up. Results We analyzed data from 174 RA patients with a median follow-up of 1.9 years (IQR 1.3–2.4); 117 (67%) were overweight/obese at baseline, and 53 (31%) lost ≥5 kg during follow-up. Patients who were overweight/obese and lost ≥5 kg had three-fold increased odds of disease activity improvement compared to those who did not (OR 3.03, 95%CI 1.18–7.83). Among those who were overweight/obese at baseline, each kilogram weight loss was associated with CDAI improvement of 1.15 (95%CI 0.42–1.88). Our study was limited by using clinical data from a single center without fixed intervals for assessments. Conclusion Clinically relevant weight loss (≥5 kg) was associated with improved RA disease activity in the routine clinical setting. Further studies are needed for replication and to evaluate the effect of prospective weight loss interventions on RA disease activity. PMID:29606976

Impact of body weight on the achievement of minimal disease activity in patients with rheumatic diseases: a systematic review and meta-analysis.

PubMed

Lupoli, Roberta; Pizzicato, Paolo; Scalera, Antonella; Ambrosino, Pasquale; Amato, Manuela; Peluso, Rosario; Di Minno, Matteo Nicola Dario

2016-12-13

In this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflammatory disease and some studies suggested that obese patients with rheumatic diseases exhibit a lower rate of low disease activity achievement during treatment with anti-rheumatic drugs. A systematic search was performed in major electronic databases (PubMed, Web of Science, Scopus, Embase) to identify studies reporting MDA achievement in obese and/or overweight patients with RA or PsA and in normal-weight RA or PsA control subjects. Results were expressed as Odds Ratios (ORs) with pertinent 95% Confidence Intervals (95%CIs). We included 17 studies (10 on RA and 7 on PsA) comprising a total of 6693 patients (1562 with PsA and 5131 with RA) in the analysis. The MDA achievement rate was significantly lower in obese patients than in normal-weight subjects (OR 0.447, 95% CI 0.346-0.577, p < 0.001, I 2  = 62.6%, p < 0.001). Similarly, overweight patients showed a significantly lower prevalence of MDA achievement than normal-weight subjects (OR 0.867, 95% CI 0.757-0.994, p = 0.041, I 2  = 64%, p = 0.007). Interestingly, the effect of obesity on MDA was confirmed when we separately analyzed data on patients with RA and patients with PsA. In contrast, when we evaluated the effect of overweight, our results were confirmed for PsA but not for RA. A meta-regression analysis showed that follow-up duration, age, male sex, and treatment duration are covariates significantly affecting the effect of obesity/overweight on MDA achievement. The results of our meta-analysis suggest that obesity and overweight reduce the chances to achieve MDA in patients with rheumatic diseases receiving treatment with traditional or biologic disease-modifying antirheumatic

Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

PubMed

Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Effect of self-efficacy and physical activity goal achievement on arthritis pain and quality of life in patients with rheumatoid arthritis.

PubMed

Knittle, Keegan P; De Gucht, Véronique; Hurkmans, Emalie J; Vlieland, Thea P M Vliet; Peeters, André J; Ronday, H Karel; Maes, Stan

2011-11-01

To examine physical activity and achievement of physical activity goals in relation to self-reported pain and quality of life among patients with rheumatoid arthritis (RA). At baseline, 271 patients with RA were asked to specify a physical activity goal, and filled in questionnaires assessing physical activity, motivation, and self-efficacy for physical activity, arthritis pain, and quality of life. Six months later, patients indicated to what extent they had achieved their baseline physical activity goal and completed the same set of questionnaires. These data were used to construct multiple mediation models that placed physical activity and physical activity goal achievement as mediators between self-efficacy and motivation on one hand, and arthritis pain and quality of life on the other. A total of 106 patients with RA completed both questionnaires. Self-efficacy at baseline predicted subsequent level of physical activity and achievement of physical activity goals. Goal achievement had a direct effect upon quality of life outcomes. Bootstrapping confidence intervals revealed indirect effects of self-efficacy upon arthritis pain and quality of life through goal achievement, but not through physical activity. Higher levels of self-efficacy for physical activity increase the likelihood that patients will achieve their physical activity goals. Achievement of physical activity goals seems to be related to lower self-reported arthritis pain, and higher levels of quality of life. In practice, clinicians can foster self-efficacy and goal achievement by assisting patients in setting realistic and attainable exercise goals, developing action plans, and by providing feedback on goal progress. Copyright © 2011 by the American College of Rheumatology.

Periodontal Therapy Reduces the Severity of Active Rheumatoid Arthritis in Patients Treated With or Without Tumor Necrosis Factor Inhibitors

PubMed Central

Ortiz, P; Bissada, NF; Palomo, L; Han, YW; Al-Zahrani, MS; Panneerselvam, A; Askari, A

2010-01-01

Background Rheumatoid arthritis (RA) and periodontitis (PD) are common chronic inflammatory conditions. Recent studies have shown a beneficial effect of periodontal treatment on reducing the severity of active RA. This study was undertaken to further examine the effect of non-surgical periodontal treatment on signs and symptoms of RA in patients treated with or without anti-Tumor Necrosis Factor (TNF)-α medications. The effect of anti-TNF-α therapy on periodontitis also was assessed. Methods Forty participants diagnosed with moderate/severe RA (under treatment for RA) and severe periodontitis were randomly assigned to receive initial non-surgical periodontal therapy with scaling/root planing and oral hygiene instructions (n=20) or no periodontal therapy (n=20). To control RA, all participants had been using disease-modifying anti-rheumatic drugs (DMARDs), and 20 had been using anti-TNF-α in addition to DMARDs before randomization. Periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), gingival (GI) and plaque (PI) indices, RA disease activity score (DAS-28) and erythrocyte sedimentation rate (ESR) were measured at baseline and six weeks afterwards. Linear mixed models were used to identify significant differences between subjects receiving periodontal treatment and those who did not. Results Patients receiving periodontal treatment showed a significant decrease in the mean DAS28, ESR (p < 0.001) and serum TNF-α (p < 0.05). There was no statistically significant decrease in these parameters in those patients not receiving periodontal treatment. Anti- TNF-α therapy resulted in a significant improvement in CAL, PD, BOP and GI. Conclusions Non-surgical periodontal therapy had a beneficial effect on signs and symptoms of RA regardless of the medications used to treat this condition. Anti-TNF-α therapy without periodontal treatment has no significant effect on the periodontal condition. PMID:19335072

Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.

PubMed

Gheita, Tamer A; Sayed, Safaa; Gheita, Heba A; Kenawy, Sanaa A

2016-03-01

To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001). Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease.

PubMed

Canavan, James B; Scottà, Cristiano; Vossenkämper, Anna; Goldberg, Rimma; Elder, Matthew J; Shoval, Irit; Marks, Ellen; Stolarczyk, Emilie; Lo, Jonathan W; Powell, Nick; Fazekasova, Henrieta; Irving, Peter M; Sanderson, Jeremy D; Howard, Jane K; Yagel, Simcha; Afzali, Behdad; MacDonald, Thomas T; Hernandez-Fuentes, Maria P; Shpigel, Nahum Y; Lombardi, Giovanna; Lord, Graham M

2016-04-01

Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn's blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown. To define the optimum population for Treg cell therapy in CD, CD4(+)CD25(+)CD127(lo)CD45RA(+) and CD4(+)CD25(+)CD127(lo)CD45RA(-) Treg subsets were isolated from patients' blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. Tregs can be expanded from the blood of patients with CD to potential target dose within 22-24 days. Expanded CD45RA(+) Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA(-) Tregs. CD45RA(+) Tregs highly express α4β7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA(+) Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA(+) Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa. CD4(+)CD25(+)CD127(lo)CD45RA(+) Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and are responsive to change after biologic therapy.

PubMed

Vlad, Violeta; Berghea, Florian; Micu, Mihaela; Varzaru, Luminita; Bojinca, Mihai; Milicescu, Mihaela; Ionescu, Ruxandra; Naredo, Esperanza

2015-09-01

To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.

Platelet-Derived Growth Factor Receptor Activation Promotes the Prodestructive Invadosome-Forming Phenotype of Synoviocytes from Patients with Rheumatoid Arthritis.

PubMed

Charbonneau, Martine; Lavoie, Roxane R; Lauzier, Annie; Harper, Kelly; McDonald, Patrick P; Dubois, Claire M

2016-04-15

Fibroblast-like synoviocytes (FLS) play a major role in invasive joint destruction in rheumatoid arthritis (RA). This prodestructive phenotype has been shown to involve autocrine TGF-β that triggers formation of matrix-degrading invadosomes through molecular mechanisms that are not fully elucidated. The platelet-derived growth factor (PDGF) receptor (PDGFR) family of receptor tyrosine kinases (RTK) has been shown to cooperate with TGF-β in various pathological conditions. We therefore sought to determine whether RTK activity played a role in invadosome biogenesis. We demonstrated that, among the common RTKs, PDGFR-αβ was specifically phosphorylated in FLS from RA patients. Phosphorylation of PDGFR-αβ was also elevated in RA synovial tissues. Interference with PDGFR activation or PDGF neutralization inhibited invadosome formation in RA synoviocytes, indicating the presence of an autocrine PDGFR activation loop that involved endogenous PDGF. Among the PDGF-A-D isoforms, only PDGF-B was found both significantly elevated in FLS lines from RA patients, and related to high-invadosome forming cells. Addition of TGF-β upregulated invadosome formation, PDGF-B mRNA expression, and phosphorylation of PDGFR. All of these functions were efficiently suppressed by TGF-β neutralization or interference with the Smad/TβR1or PI3K/Akt pathway. Among the class 1 PI3K family proteins known to be expressed in RA synoviocytes, PI3Kα was selectively involved in PDGF-B expression, whereas both PI3Kα and PI3Kδ participated in invadosome formation. Our findings demonstrate that PDGFR is a critical RTK required for the prodestructive phenotype of RA synovial cells. They also provide evidence for an association between autocrine TGF-β and PDGFR-mediated invadosome formation in RA synoviocytes that involves the production of PDGF-B induced by TGF-β. Copyright © 2016 by The American Association of Immunologists, Inc.

[Pattern of serum cytokines in patients with rheumatoid artritis according to PPD reactivity].

PubMed

de León Pandolfi, Darío Ponce; Pastor Asurza, César; Beraun, Yasmina; Acevedo-Vásquez, Eduardo; Sánchez-Torres, Alfredo; Alfaro Lozano, José; Perich Campos, Risto; Cucho Venegas, Mariano; Gutiérrez Villafuerte, César; Sánchez Schwartz, César

2006-11-01

We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. Forty RA patients and 21 controls were enrolled. Those with an induration < 5mm were considered as negative and those with ≥ 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

Post-stroke infection: a role for IL-1ra?

PubMed

Tanzi, Pat; Cain, Kevin; Kalil, Angela; Zierath, Dannielle; Savos, Anna; Gee, J Michael; Shibata, Dean; Hadwin, Jessica; Carter, Kelly; Becker, Kyra

2011-04-01

Infection is common following stroke and is independently associated with worse outcome. Clinical studies suggest that infections occur more frequently in those individuals with stroke-induced immunologic dysfunction. This study sought to explore the contribution of immunomodulatory cytokines and hormones to lymphocyte function and infection risk. Patients (N = 112) were enrolled as soon as possible after the onset of ischemic stroke. Blood was drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and lymphocyte function at 72 h after stroke onset; infections were censored through 21 days after stroke onset. Infection occurred in 25% of patients. Stroke severity was the most important predictor of infection risk. Increased plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at 72 h after stroke onset were associated with risk of subsequent infection. After controlling for stroke severity, only IL-1ra was independently associated with infection risk, and the degree of risk was consistent throughout the post-stroke period. Infection, but not IL-1ra itself, was associated with worse outcome at 3 months. In this study cohort, increased plasma IL-1ra was independently associated with the risk of post-stroke infection. Further studies are needed to validate this finding, which could have important implications for stroke therapy.

The association between disease activity and NT-proBNP in 238 patients with rheumatoid arthritis: a 10-year longitudinal study

PubMed Central

Provan, Sella A; Angel, Kristin; Ødegård, Sigrid; Mowinckel, Petter; Atar, Dan; Kvien, Tore K

2008-01-01

Introduction Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). Methods Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. Results C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). Conclusion CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated. PMID:18573197

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.

PubMed

Michaud, Kaleb; Berglind, Niklas; Franzén, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D; Ho, Meilien; Holmqvist, Marie; Horne, Laura; Inoue, Eisuke; Nyberg, Fredrik; Pappas, Dimitrios A; Reed, George; Symmons, Deborah; Tanaka, Eiichi; Tran, Trung N; Verstappen, Suzanne M M; Wesby-van Swaay, Eveline; Yamanaka, Hisashi; Askling, Johan

2016-10-01

We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes. Published by the BMJ Publishing

Expression of K2P5.1 potassium channels on CD4+ T lymphocytes correlates with disease activity in rheumatoid arthritis patients.

PubMed

Bittner, Stefan; Bobak, Nicole; Feuchtenberger, Martin; Herrmann, Alexander M; Göbel, Kerstin; Kinne, Raimund W; Hansen, Anker J; Budde, Thomas; Kleinschnitz, Christoph; Frey, Oliver; Tony, Hans-Peter; Wiendl, Heinz; Meuth, Sven G

2011-02-11

CD4+ T cells express K(2P)5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K(2P)5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K(2P)5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Expression levels of K(2P)5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K(2P)5.1. K(2P)5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K(2P)5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K(2P)5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Disease activity in RA patients correlates strongly with K(2P)5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K(2P)5.1 as a potential biomarker for disease activity and differential diagnosis.

Activity concentrations of ²²⁶Ra, ²³²Th and ⁴⁰K in brands of fertilisers used in Nigeria.

PubMed

Jibiri, N N; Fasae, K P

2012-01-01

The activity concentration of naturally occurring radionuclides ⁴⁰K, ²²⁶Ra and ²³²Th have been measured in different brands of fertiliser samples sold to farmers in retail markets in six commercial cities in southwestern Nigeria. Gamma ray spectroscopy was employed in the measurements of these radionuclides. The results of measurements showed that the average activity concentration of ⁴⁰K in the nitrogen, phosphorus and potassium fertilisers across the cities varied from 3972.0 ± 416.9 to 5089.3 ± 111.3 Bq kg⁻¹, 9.9 ± 7.3 to 450.6 ± 14.3 Bq kg⁻¹ for ²²⁶Ra, while for ²³²Th it varied from less than lower limit of detection to 15.1 ± 2.8 Bq kg⁻¹. The activity concentrations of ⁴⁰K, ²²⁶Ra and ²³²Th in single super phosphate (SSP) fertilisers and phosphate rocks were also determined. However, high activity concentrations of ²²⁶Ra were obtained in the SSP fertiliser and phosphate rocks and in particular, two brands of fertilisers from ITL/TAK and F & C companies. The values of the activity concentration of the radionuclides in the brands of fertilisers used in Nigeria are within the range of values reported in several other countries except ⁴⁰K.

Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health-Related Quality of Life Evaluated by INCAVISA in Patients With Rheumatoid Arthritis.

PubMed

González-Gamboa, Linda Mariana; Barocio-Ramírez, Ana Karen; Rocha-Muñoz, Alberto Daniel; de Santos-Ávila, Fabiola; Meda-Lara, Rosa M; González-López, Laura; Gámez-Nava, Jorge Iván; Gómez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Durán-Barragán, Sergio; Navarro-Hernández, Rosa Elena; Pizano-Martínez, Oscar Enrique; Nuñez-Atahualpa, Lourdes; Vázquez-Del Mercado, Mónica

2016-12-01

The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.

Active matrix metalloproteinase-8 and periodontal bacteria depending on periodontal status in patients with rheumatoid arthritis.

PubMed

Kirchner, A; Jäger, J; Krohn-Grimberghe, B; Patschan, S; Kottmann, T; Schmalz, G; Mausberg, R F; Haak, R; Ziebolz, D

2017-08-01

The aim of this clinical cross-sectional study was to determine the level of active matrix metalloproteinase-8 (aMMP-8) and periodontal pathogenic bacteria in gingival crevicular fluid in patients with rheumatoid arthritis (RA) with varying periodontal conditions. In total, 103 patients with RA and 104 healthy controls (HC) were included. The assessment of periodontal status included periodontal probing depth, bleeding on probing and clinical attachment loss. Periodontal disease was classified as healthy/mild, moderate or severe. For the determination of aMMP-8 levels using enzyme-linked immunosorbent assay and periodontal pathogenic bacteria using polymerase chain reaction, samples of gingival crevicular fluid were taken from the deepest gingival pockets. The statistical analyses used included a Mann-Whitney U-test, a chi-squared test or a Fisher's exact test, and the significance level was set at α = 5%. We found that 65% of patients with RA and 79% of HC had moderate to severe periodontal disease (p = 0.02). The prevalence of periodontal pathogens was almost equal (p > 0.05). Furthermore, depending on periodontal disease severity only minor differences in bacterial prevalence were detected. With increasing severity of periodontal disease, higher aMMP-8 levels were observed. Accordingly, a significant difference in patients with moderate periodontal disease (RA: 15.3 ± 13.8; HC: 9.1 ± 9.1; p ≤ 0.01) and severe periodontal disease (RA: 21.7 ± 13.3; HC: 13.1 ± 8.6; p = 0.07) was detected, with a greater tendency in the latter group. The increased aMMP-8 levels in the RA group indicate that the presence of RA appears to have an influence on the host response at a comparable level of bacterial load and periodontal disease severity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of interleukin-1 receptor antagonist (IL-1Ra) gene 86 bp VNTR polymorphism on recurrent pregnancy loss: a case-control study.

PubMed

Hajizadeh, Yasamin Sayed; Emami, Elina; Nottagh, Marina; Amini, Zahra; Maroufi, Nazila Fathi; Azimian, Saba Haj; Isazadeh, Alireza

2017-05-26

Objective Recurrent pregnancy loss (RPL) is a heterogeneous disease which is defined as two or more consecutive fetal losses during early pregnancy. Interleukin-1 receptor antagonist (IL-1Ra) is a anti-inflammatory cytokine, which inhibits IL-1 activity by binding to its receptors. The aim of this study was to investigate the association between RPL and IL-1Ra intron 2 polymorphism (86 bp VNTR) in Iranian women. Materials and methods In this case control study, genetic polymorphism was studied in 140 RPL patients and 140 healthy women as controls. Genomic DNA was extracted from the blood samples and polymorphism analysis was performed using the polymerase chain reaction (PCR) method. Finally, the data obtained were analyzed by statistical software. Results We found an increased frequency of the IL-1Ra 1/1 genotype in the case group compared to the control group. Whereas, the frequency of IL-1Ra genotype 1/2 was higher in control group than in the case group. However, we did not observe an association between IL-1Ra 86 bp VNTR polymorphism in intron 2 and RPL patients (p > 0.05). Conclusion IL-1Ra VNTR polymorphism may not be a genetic factor for RPL. However, investigation of IL-1Ra polymorphism was recommended in other populations and patients with recurrent pregnancy loss.

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Patient Education in the Management of Rheumatoid Arthritis (RA)

ERIC Educational Resources Information Center

Brosseau, Lucie; Wells, George A.; Tugwell, Peter; Egan, Mary; Dubouloz, Claire-Jehanne; Welch, Vivian A.; Trafford, Laura; Sredic, Danjiel; Pohran, Kathryn; Smoljanic, Jovana; Vukosavljevic, Ivan; De Angelis, Gino; Loew, Laurianne; McEwan, Jessica; Bell, Mary; Finestone, Hillel M.; Lineker, Sydney; King, Judy; Jelly, Wilma; Casimiro, Lynn; Haines-Wangda, Angela; Russell-Doreleyers, Marion; Laferriere, Lucie; Lambert, Kim

2012-01-01

Background and purpose: The objective of this article is to create guidelines for education interventions in the management of patients ([greater than] 18 years old) with rheumatoid arthritis (RA). Methods: The Ottawa Methods Group identified and synthesized evidence from comparative controlled trials using Cochrane Collaboration methods. The…

Tofacitinib in Combination With Conventional Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis: Patient-Reported Outcomes From a Phase III Randomized Controlled Trial.

PubMed

Strand, Vibeke; Kremer, Joel M; Gruben, David; Krishnaswami, Sriram; Zwillich, Samuel H; Wallenstein, Gene V

2017-04-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient-reported outcomes (PROs) in patients with RA treated with tofacitinib or placebo in combination with conventional disease-modifying antirheumatic drugs (DMARDs). In a 12-month, phase III randomized controlled trial (ORAL Sync), patients (n = 795) with active RA and previous inadequate response to therapy with ≥1 conventional or biologic DMARD were randomized 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo advanced to 5 mg BID, or placebo to 10 mg BID, in combination with stable background DMARD therapy. PROs included patient global assessment of arthritis (PtGA), patient assessment of arthritis pain (Pain), physical function (Health Assessment Questionnaire disability index [HAQ DI]), health-related quality of life (Short Form 36 health survey [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and sleep (Medical Outcomes Study Sleep [MOS Sleep]). At month 3, statistically significant improvements from baseline versus placebo were reported in PtGA, Pain, HAQ DI, all 8 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 10 mg BID, and in PtGA, Pain, HAQ DI, 7 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 5 mg BID. Improvements were sustained to month 12. Significantly more tofacitinib-treated patients reported improvements of greater than or equal to the minimum clinically important differences at month 3 versus placebo in all PROs, except the SF-36 role-emotional domain (significant for tofacitinib 10 mg BID). Patients with active RA treated with tofacitinib combined with background conventional DMARD therapy reported sustained, significant, and clinically meaningful improvements in PROs versus placebo. © 2016, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Remission is the goal for cardiovascular risk management in patients with rheumatoid arthritis: a cross-sectional comparative study.

PubMed

Provan, Sella A; Semb, Anne Grete; Hisdal, Jonny; Stranden, Einar; Agewall, Stefan; Dagfinrud, Hanne; Angel, Kristin; Atar, Dan; Kvien, Tore K

2011-05-01

To compare markers of cardiovascular disease (CVD) risk between patients with rheumatoid arthritis (RA) in an active disease state and those with RA in remission, and to compare both groups with community controls. 113 patients with RA and 86 community controls were assessed across a panel of biomarkers for CVD. RA in remission was defined as Clinical Disease Activity Index ≤2.8. Community controls were selected at random by Statistics Norway, and controls were matched with patients in the cohorts in strata using details of age, sex and residential area. A panel of biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), total cholesterol, reactive hyperaemia index (RHI), pressure measurements, measures of arterial stiffness and intima-media thickness) were compared between patients with active RA and those with RA in remission. Both groups were compared with controls. In addition, biomarker levels were compared across subgroups based on anticyclic citrullinated peptide status, level of joint destruction and presence of extra-articular manifestations. Patients with active RA had significantly higher levels of NT-proBNP, brachial systolic pressure, augmentation index and central systolic pressure but lower cholesterol than patients in remission and controls. In addition, patients with active RA had significantly higher levels of pulse wave velocity and worse RHI than patients in remission. Comparison across other subgroups gave less consistent differentiations in levels of CVD risk markers. Patients with active RA, but not those in remission, had significantly increased levels of CVD risk markers. These results link inflammatory activity to markers of CVD risk in patients with RA and may indirectly support the notion that remission in RA confers diminished cardiovascular morbidity.

Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

PubMed

Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

2017-06-01

Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

RA Construction KC, LLC Information Sheet

EPA Pesticide Factsheets

RA Construction KC, LLC (the Company) is located in Gladstone, Missouri. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Kansas City, Missouri.

The RA Role Revisited: Differences in Perspectives of RA Responsibilities.

ERIC Educational Resources Information Center

Schuh, John H.; And Others

1982-01-01

Determined resident assistants' (RA) role perceptions of students, parents, faculty, and administrators, full-time professional residence life staff, and resident assistants. Compared various constituent groups' perceptions of the RA role. (RC)

Infliximab in active early rheumatoid arthritis

PubMed Central

Breedveld, F; Emery, P; Keystone, E; Patel, K; Furst, D; Kalden, J; St, C; Weisman, M; Smolen, J; Lipsky, P; Maini, R

2004-01-01

Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA). Methods: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX (infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group. Results: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet. Conclusions: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity. PMID:14722203

The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis.

PubMed

De Winter, Liesbeth M; Geusens, Piet; Lenaerts, Jan; Vanhoof, Johan; Stinissen, Piet; Somers, Veerle

2016-06-07

Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH-RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti-UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by

Impact of bariatric surgery on patients with rheumatoid arthritis

PubMed Central

Sparks, Jeffrey A.; Halperin, Florencia; Karlson, Jonathan C.; Karlson, Elizabeth W.; Bermas, Bonnie L.

2015-01-01

Objective We investigated the effect of weight loss after bariatric surgery among patients with rheumatoid arthritis (RA). Methods We conducted a retrospective cohort study of RA patients who underwent bariatric surgery (Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or sleeve gastrectomy) at two medical centers. We obtained anthropometrics, laboratory values, RA disease activity, and medication use at baseline (prior to surgery), at six and twelve months post-surgery, and at most recent follow-up visits. RA disease activity was determined by clinical or validated measures. At each post-surgical visit, characteristics were compared to baseline. Results We identified 53 RA patients who underwent bariatric surgery. At baseline prior to surgery, mean body mass index was 47.8 kg/m2 (SD 7.7), mean weight was 128.2 kg (SD 24.1), and 57% had moderate/high RA disease activity. Twelve months post-surgery, subjects lost a mean of 41.0 kg (SD 17.3), 70% (SD 24) of excess weight (P<0.001). RA disease activity significantly improved at post-surgical visits (P<0.001). At 12 months post-surgery, 6% had moderate/high disease activity compared to 57% at baseline (P<0.001). At most recent follow-up (mean 5.8 years [SD 3.2] after surgery), 74% were in remission compared to 26% at baseline (P<0.001). Subjects had significantly lower erythrocyte sedimentation rate, C-reactive protein, and RA-related medication use at follow-up visits compared to baseline (P<0.05). Conclusion After substantial weight loss from bariatric surgery, RA patients had lower disease activity, decreased serum inflammatory markers, and less RA-related medication usage. Weight loss may be an important non-pharmacologic strategy to reduce RA disease activity. However, other factors, such as improved efficacy of medications, improved physical activity, and metabolic changes, may also have contributed to these post-surgical improvements. PMID:26018243

Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the bone marrow toxicity of the methotrexate in RA patients.

PubMed

Jekic, Biljana; Lukovic, Ljiljana; Bunjevacki, Vera; Milic, Vera; Novakovic, Ivana; Damnjanovic, Tatjana; Milasin, Jelena; Popovic, Branka; Maksimovic, Nela; Damjanov, Nemanja; Radunovic, Goran; Kovacevic, Ljiljana; Krajinovic, Maja

2013-03-01

Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G > T and 452 C > T), CCND1 (870 A > G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as non-responders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p = 0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p = 0.003). No other significant association were observed. The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T > G polymorphism may have high predictive value for myelosuppression in RA patients.

Measurement of interleukin-1 receptor antagonist in patients with systemic lupus erythematosus could predict renal manifestation of the disease.

PubMed

Brugos, Boglarka; Kiss, Emese; Dul, Csaba; Gubisch, Wolfgang; Szegedi, Gyula; Sipka, Sandor; Zeher, Margit

2010-09-01

Interleukin-1 receptor antagonist (IL-1Ra) is a good indicator of disease activity in patients with systemic lupus erythematosus (SLE). Glucocorticosteroids are the most frequently used drugs in SLE. Our goal was to compare IL-1Ra activity in SLE patients with and without renal involvement and to determine the effect of different dosage of glucocorticosteroids used in 17 patients with active SLE without nephritis, 7 patients with inactive lupus nephritis (LN), and 8 patients with active LN, along with 10 healthy controls. IL-1Ra levels were measured in the serum of SLE patients by Human Luminex [100] analyzer. Both in patients with active SLE without nephritis and in patients with LN, serum levels of IL-1Ra (p<0.001) were significantly higher compared with those in the controls. IL-1Ra was significantly higher in patients with active LN than in patients with inactive LN (p = 0.028). The use of methylprednisolone was significantly higher in the active LN group compared with the inactive LN group (p = 0.013). SLE patients with higher IL-1Ra are at lower risk for developing nephritis. The higher doses of glucocorticosteroids needed in active LN could be due to steroid resistance and IL-1Ra polymorphism. Measurement of IL-1Ra levels in SLE patients could help to predict future renal involvement. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients

PubMed Central

MUÑOZ-VALLE, J F; VÁZQUEZ-DEL MERCADO, M; GARCÍA-IGLESIAS, T; OROZCO-BAROCIO, G; BERNARD-MEDINA, G; MARTÍNEZ-BONILLA, G; BASTIDAS-RAMÍREZ, B E; NAVARRO, A D; BUENO, M; MARTÍNEZ-LÓPEZ, E; BEST-AGUILERA, C R; KAMACHI, M; ARMENDÁRIZ-BORUNDA, J

2003-01-01

During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-γ was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease. PMID:12562402

Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial.

PubMed

Bechman, Katie; Sin, Fang En; Ibrahim, Fowzia; Norton, Sam; Matcham, Faith; Scott, David Lloyd; Cope, Andrew; Galloway, James

2018-01-01

Tapering of anti-tumour necrosis factor (TNF) therapy appears feasible, safe and effective in selected patients with rheumatoid arthritis (RA). Depression is highly prevalent in RA and may impact on flare incidence through various mechanisms. This study aims to investigate if psychological states predict flare in patients' dose tapering their anti-TNF therapy. This study is a post-hoc analysis of the Optimizing TNF Tapering in RA trial, a multicentre, randomised, open-label study investigating anti-TNF tapering in RA patients with sustained low disease activity. Patient-reported outcomes (Health Assessment Questionnaire, EuroQol 5-dimension scale, Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F), 36-Item Short Form Survey (SF-36)) were collected at baseline. The primary outcome was flare, defined as an increase in 28-joint count Disease Activity Score (DAS28) ≥0.6 and ≥1 swollen joint. Discrete-time survival models were used to identify patient-reported outcomes that predict flare. Ninety-seven patients were randomised to taper their anti-TNF dose by either 33% or 66%. Forty-one patients flared. Higher baseline DAS28 score was associated with flare (adjusted HR 1.96 (95% CI 1.18 to 3.24), p=0.01). Disability (SF-36 physical component score), fatigue (FACIT-F) and mental health (SF-36 mental health subscale (MH)) predicted flare in unadjusted models. In multivariate analyses, only SF-36 MH remained a statistically significant predictor of flare (adjusted HR per 10 units 0.74 (95% CI 0.60 to 0.93), p=0.01). Baseline DAS28 and mental health status are independently associated with flare in patients who taper their anti-TNF therapy. Fatigue and function also associate with flare but the effect disappears when adjusting for confounders. Given these findings, mental health and functional status should be considered in anti-TNF tapering decisions in order to optimise the likelihood of success. EudraCT Number: 2010-020738-24; ISRCTN: 28955701

Methotrexate as a preferential cyclooxygenase 2 inhibitor in whole blood of patients with rheumatoid arthritis.

PubMed

Mello, S B; Barros, D M; Silva, A S; Laurindo, I M; Novaes, G S

2000-05-01

To investigate the regulation of whole-blood cyclooxygenase-1 and -2 (COX-2 and COX-1) activities by methotrexate (MTX) in rheumatoid arthritis (RA) patients. Whole blood was withdrawn from nine healthy volunteers, 12 RA patients treated with MTX (RA/MTX) and six RA patients treated with chloroquine (RA/CQ). COX-1 activity was quantified as platelet thromboxane B(2) production in unstimulated blood and COX-2 activity was measured as prostaglandin E(2) (PGE(2)) production in whole blood stimulated with LPS. Thromboxane B(2) and PGE(2) were measured by radioimmunoassay. We studied the drug effect in vitro by direct incubation of MTX with blood obtained from normal donors. Ex vivo assays were performed with blood collected from RA/MTX and RA/CQ patients. The influence of serum factors on enzyme activities was analysed in blood collected from normal donors and incubated with RA/MTX, autologous or heterologous serum. In vitro assays showed no direct action of MTX on the activity of either enzyme. Assays performed with blood from RA/MTX patients showed preferential inhibition of COX-2 activity (PGE(2) = 10.11 +/- 2.42 ng/ml) when compared with blood of normal donors (PGE(2) = 37.7 +/- 4.36 ng/ml; P = 0.001). Inhibition of COX-2 activity was also observed when blood of normal donors was co-incubated with RA/MTX serum. Our results clearly show that the anti-inflammatory action of low-dose MTX is partly mediated by a serum factor induced by MTX or a MTX metabolite that preferentially inhibits the activity of COX-2.

Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity.

PubMed

Haliloglu, Sema; Carlioglu, Ayse; Akdeniz, Derya; Karaaslan, Yasar; Kosar, Ali

2014-09-01

Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain and the presence of specific tender points. The prevalence of FM has been estimated at 2-7 % of the general global population. The presence of FM in several rheumatic diseases with a structural pathology has been reported as 11-30 %. The objectives of this study were to determine the prevalence of FM and to evaluate the possible relationship between FM existence and disease activity among rheumatic diseases. The study group included 835 patients--197 rheumatoid arthritis (RA), 67 systemic lupus erythematosus (SLE), 119 ankylosing spondylitis (AS), 238 osteoarthritis (OA), 14 familial Mediterranean fever (FMF), 53 Behçet's disease (BD), 71 gout, 25 Sjögren's syndrome (SS), 20 vasculitis, 29 polymyalgia rheumatica (PMR), and two polymyositis (PM)--with or without FM. Recorded information included age, gender, laboratory parameters, presence of fatigue, and disease activity indexes. The prevalence of FM in patients with rheumatologic diseases was found to be 6.6 % for RA, 13.4 % for SLE, 12.6 % for AS, 10.1 % for OA, 5.7 % for BD, 7.1 % for FMF, 12 % for SS, 25 % for vasculitis, 1.4 % for gout, and 6.9 % for PMR. One out of two patients with PM was diagnosed with FM. Some rheumatologic cases (AS, OA) with FM were observed mostly in female patients (p = 0.000). Also, there were significant correlations between disease activity indexes and Fibromyalgia Impact Questionnaire scores for most rheumatologic patients (RA, AS, OA, and BD) (p < 0.05; respectively, r = 0.6, 0.95, 0.887, and 1). Concomitant FM is a common clinical problem in rheumatologic diseases, and its recognition is important for the optimal management of these diseases. Increased pain, physical limitations, and fatigue may be interpreted as increased activity of these diseases, and a common treatment option is the prescription of higher doses of biologic agents or corticosteroids. Considerations of the FM component in the management

Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients.

PubMed

Gossec, Laure; Kirwan, John Richard; de Wit, Maarten; Balanescu, Andra; Gaujoux-Viala, Cecile; Guillemin, Francis; Rat, Anne-Christine; Saraux, Alain; Fautrel, Bruno; Kvien, Tore K; Dougados, Maxime

2018-06-01

The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.

Outcomes and costs of incorporating a multibiomarker disease activity test in the management of patients with rheumatoid arthritis.

PubMed

Michaud, Kaleb; Strand, Vibeke; Shadick, Nancy A; Degtiar, Irina; Ford, Kerri; Michalopoulos, Steven N; Hornberger, John

2015-09-01

The multibiomarker disease activity (MBDA) blood test has been clinically validated as a measure of disease activity in patients with RA. We aimed to estimate the effect of the MBDA test on physical function for patients with RA (based on HAQ), quality-adjusted life years and costs over 10 years. A decision analysis was conducted to quantify the effect of using the MBDA test on RA-related outcomes and costs to private payers and employers. Results of a clinical management study reporting changes to anti-rheumatic drug recommendations after use of the MBDA test informed clinical utility. The effect of treatment changes on HAQ was derived from 5 tight-control and 13 treatment-switch trials. Baseline HAQ scores and the HAQ score relationship with medical costs and quality of life were derived from published National Data Bank for Rheumatic Diseases data. Use of the MBDA test is projected to improve HAQ scores by 0.09 units in year 1, declining to 0.02 units after 10 years. Over the 10 year time horizon, quality-adjusted life years increased by 0.08 years and costs decreased by US$457 (cost savings in disability-related medical costs, US$659; in productivity costs, US$2137). The most influential variable in the analysis was the effect of the MBDA test on clinician treatment recommendations and subsequent HAQ changes. The MBDA test aids in the assessment of disease activity in patients with RA by changing treatment decisions, improving the functional status of patients and cost savings. Further validation is ongoing and future longitudinal studies are warranted. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

PubMed

Kubo, Satoshi; Yamaoka, Kunihiro; Amano, Koichi; Nagano, Shuji; Tohma, Shigeto; Suematsu, Eiichi; Nagasawa, Hayato; Iwata, Kanako; Tanaka, Yoshiya

2017-08-01

To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

PubMed Central

Szalay, Balázs; Cseh, Áron; Mészáros, Gergő; Kovács, László; Balog, Attila; Vásárhelyi, Barna

2014-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca2+ level, mitochondrial Ca2+ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca2+ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca2+ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca2+ level was higher than controls at baseline. The cytoplasmic Ca2+ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca2+ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. PMID:25098248

Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial

PubMed Central

Bechman, Katie; Sin, Fang En; Ibrahim, Fowzia; Norton, Sam; Matcham, Faith; Scott, David Lloyd; Cope, Andrew; Galloway, James

2018-01-01

Background Tapering of anti-tumour necrosis factor (TNF) therapy appears feasible, safe and effective in selected patients with rheumatoid arthritis (RA). Depression is highly prevalent in RA and may impact on flare incidence through various mechanisms. This study aims to investigate if psychological states predict flare in patients’ dose tapering their anti-TNF therapy. Methods This study is a post-hoc analysis of the Optimizing TNF Tapering in RA trial, a multicentre, randomised, open-label study investigating anti-TNF tapering in RA patients with sustained low disease activity. Patient-reported outcomes (Health Assessment Questionnaire, EuroQol 5-dimension scale, Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F), 36-Item Short Form Survey (SF-36)) were collected at baseline. The primary outcome was flare, defined as an increase in 28-joint count Disease Activity Score (DAS28) ≥0.6 and ≥1 swollen joint. Discrete-time survival models were used to identify patient-reported outcomes that predict flare. Results Ninety-seven patients were randomised to taper their anti-TNF dose by either 33% or 66%. Forty-one patients flared. Higher baseline DAS28 score was associated with flare (adjusted HR 1.96 (95% CI 1.18 to 3.24), p=0.01). Disability (SF-36 physical component score), fatigue (FACIT-F) and mental health (SF-36 mental health subscale (MH)) predicted flare in unadjusted models. In multivariate analyses, only SF-36 MH remained a statistically significant predictor of flare (adjusted HR per 10 units 0.74 (95% CI 0.60 to 0.93), p=0.01). Conclusions Baseline DAS28 and mental health status are independently associated with flare in patients who taper their anti-TNF therapy. Fatigue and function also associate with flare but the effect disappears when adjusting for confounders. Given these findings, mental health and functional status should be considered in anti-TNF tapering decisions in order to optimise the likelihood of success. Trial

Evaluation of learned helplessness, self-efficacy and disease activity, functional capacity and pain in Argentinian patients with rheumatoid arthritis.

PubMed

Vergara, F; Rosa, J; Orozco, C; Bertiller, E; Gallardo, M A; Bravo, M; Catay, E; Collado, V; Gómez, G; Sabelli, M; García, M V; Rosemffet, M G; Citera, G; Schneeberger, E E; Catoggio, L J; Soriano, E R

2017-01-01

To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.

Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials.

PubMed

Wallenstein, Gene V; Kanik, Keith S; Wilkinson, Bethanie; Cohen, Stanley; Cutolo, Maurizio; Fleischmann, Roy; Genovese, Mark C; Gomez Reino, Juan; Gruben, David; Kremer, Joel; Krishnaswami, Sriram; Lee, Eun Bong; Pascual-Ramos, Virginia; Strand, Vibeke; Zwillich, Samuel H

2016-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we investigated the effects of tofacitinib on patient-reported outcomes (PRO) in patients with active RA. Two, 6-month, double-blind, placebo-controlled Phase 2b studies were performed. The combination study evaluated patients with inadequate response to methotrexate who received tofacitinib 1-15 mg twice daily (BID), 20 mg once daily or placebo, on background methotrexate. In the monotherapy study, patients with inadequate response to disease-modifying anti-rheumatic drugs received tofacitinib 1-15 mg BID, adalimumab 40 mg once every other week or placebo. PROs measured were: Patient's Assessment of Arthritis Pain (PAAP), Patient's Assessment of Disease Activity, HAQ-DI, FACIT-F and SF-36. In the combination study (n=507), significant improvements (p<0.05) versus placebo were observed at Week 12 in PAAP (visual analogue scale) and HAQ-DI for all tofacitinib groups. In the monotherapy study (n=384), significant improvements in PAAP were observed at Week 12 for tofacitinib 5, 10 and 15 mg BID, and in HAQ-DI for tofacitinib 3, 5, 10 and 15 mg BID. Significant improvements versus placebo were seen at Week 2 in PAAP (both studies) and HAQ‑DI (monotherapy study) with tofacitinib, and were maintained throughout each study. In both studies, improvements in several domains of the SF-36 in the tofacitinib groups were observed at Weeks 12 and 24. In patients with active RA, tofacitinib, either in combination with methotrexate or as monotherapy, demonstrated rapid and sustained improvement in pain, physical functioning and health-related quality of life.

Polymorphisms of genes encoding tumor necrosis factor-alpha, interleukin-10, cluster of differentiation-14 and interleukin-1ra in critically ill patients.

PubMed

Surbatovic, Maja; Grujic, Krasimirka; Cikota, Bojana; Jevtic, Miodrag; Filipovic, Nikola; Romic, Predrag; Strelic, Natasa; Magic, Zvonko

2010-09-01

The aim of the study was to determine whether distributions of tumor necrosis factor (TNF)-α(308), interleukin (IL)-10(1082), CD14(159), and IL-1ra gene intron 2 genotypes in critically ill patients are associated with outcome, underlying cause of sepsis, and type of microorganism. Blood samples from 106 critically ill white patients were genotyped by method based on polymerase chain reaction for TNF-α(308), IL-10(1082), CD14(159), and IL-1ra gene intron 2. All patients with TNF-α(308)AA genotype survived; relative risk (RR) of death in patients with AG was 3.250 and with GG, 1.923 (P < .01). In patients with Gram-positive sepsis, IL-10(1082)AA and then AG genotypes were the most frequent ones (odds ratio [OR], 18.67 and 7.20, respectively; P < .01). When comparing IL-10(1082)AA with AG, RR of pancreatitis was 1.80 and OR was 3.40. When AA and GG were compared, RR was 7.33 and OR was 20.00. In patients with GG, RR of peritonitis was 4.07 and OR was 5.88 (P < .01). In patients with Gram-positive sepsis, CD14(159)CT was the most frequent one with OR of 5.25. Distribution of 6 IL-1ra gene intron 2 genotypes showed no significant association. Distribution of TNF-α(308) genotypes is associated with outcome, IL-10(1082) with type of microorganism and underlying cause of sepsis, and CD14(159) with type of microorganism. Copyright © 2010. Published by Elsevier Inc.

Mapping the spatial distribution and activity of (226)Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data.

PubMed

Varley, Adam; Tyler, Andrew; Smith, Leslie; Dale, Paul; Davies, Mike

2016-03-01

Radium ((226)Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of (226)Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as (226)Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for (226)Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity (<3 Bq g(-1)) occurring at depth (>0.4m), that conventional gross counting algorithms

De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus.

PubMed

Um, Soo-Jong; Youn, Hye Sook; Kim, Eun-Joo

2014-02-21

Transcriptional activity of the retinoic acid receptor (RAR) is regulated by diverse binding partners, including classical corepressors and coactivators, in response to its ligand retinoic acid (RA). Recently, we identified a novel corepressor of RAR called the retinoic acid resistance factor (RaRF) (manuscript submitted). Here, we report how adenovirus E1A stimulates RAR activity by associating with RaRF. Based on immunoprecipitation (IP) assays, E1A interacts with RaRF through the conserved region 2 (CR2), which is also responsible for pRb binding. The first coiled-coil domain of RaRF was sufficient for this interaction. An in vitro glutathione-S-transferase (GST) pull-down assay was used to confirm the direct interaction between E1A and RaRF. Further fluorescence microscopy indicated that E1A and RaRF were located in the nucleoplasm and nucleolus, respectively. However, RaRF overexpression promoted nucleolar translocation of E1A from the nucleoplasm. Both the RA-dependent interaction of RAR with RaRF and RAR translocation to the nucleolus were disrupted by E1A. RaRF-mediated RAR repression was impaired by wild-type E1A, but not by the RaRF binding-defective E1A mutant. Taken together, our data suggest that E1A is sequestered to the nucleolus by RaRF through a specific interaction, thereby leaving RAR in the nucleoplasm for transcriptional activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data from a US-Based Registry.

PubMed

Pappas, Dimitrios A; Kent, Jeffrey D; Greenberg, Jeffrey D; Mason, Marc A; Kremer, Joel M; Holt, Robert J

2015-12-01

The goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis. The percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated. Among 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6-33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3-14.8). In this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry. Corrona, LLC.

Retinoic Acid 4-Hydroxylase Inducibility and Clinical Response to Isotretinoin in Acne Patients

PubMed Central

Wang, Frank; Kwak, Heh Shin R.; Elbuluk, Nada; Kaczmarek, Anya L.; Hamilton, Ted; Voorhees, John J.; Fisher, Gary J.; Kang, Sewon

2011-01-01

Background The cytochrome P450 enzyme CYP26 (retinoic acid 4-hydroxylase) initiates the catabolism of all-trans retinoic acid (tRA) and limits the effects of tRA. The CYP26 enzyme acts on tRA, but not 13-cis RA (isotretinoin), a retinoid used to treat severe acne. However, 13-cis RA can isomerize to tRA, which can then be metabolized by CYP26. Objective In healthy subjects, we assessed the variability of CYP26 enzymatic activity. We then investigated whether response to oral 13-cis RA among acne patients correlates with variability in CYP26 expression. Methods In healthy subjects, we isolated microsomal fractions from the epidermis of keratome biopsies and measured CYP26 enzymatic activity in untreated skin and skin treated with tRA. Enzymatic activity was determined based on rate of formation of 4-hydroxy RA (pg/min) per mg microsomal protein. Using real-time PCR we quantified CYP26 mRNA induction after tRA application in acne patients who responded or did not respond to one course of 13-cis RA. Results In normal skin (N=118), CYP26 enzymatic activity was widely variable (1–180 pg/min per mg microsomal fraction; mean 42.7 ± 3.5). Furthermore, CYP26 enzymatic activity was inducible in a dose-dependent manner in normal skin following tRA application, but not correlated with age or sex (N=29). In acne patients, CYP26 mRNA induction following 0.1% tRA application did not differ (P>0.05) between subjects who responded (N=8, 587±325 fold) or did not respond (N=8, 657±227 fold) to one course of 13-cis RA. Limitations The small number of acne patients treated with 13-cis RA was a major limitation. Conclusion Factors other than CYP26 activity may determine response to isotretinoin in acne. PMID:19525031

Impairment of neutrophil Fc gamma receptor mediated transmembrane signalling in active rheumatoid arthritis.

PubMed Central

Goulding, N J; Guyre, P M

1992-01-01

Neutrophil Fc gamma receptor (Fc gamma R) signalling responses were compared in healthy subjects, patients with definite rheumatoid arthritis (RA), ankylosing spondylitis, and osteoarthritis. The patients with A were subdivided into those with active synovitis and those with quiescent disease. Basal intracellular calcium ion concentrations in patients with inactive RA were significantly higher than in control subjects, which in turn were greater than in patients with active RA. Transient cytosolic calcium ion fluxes were observed after binding Fc gamma RII or Fc gamma RIII with specific monoclonal antibodies and cross linking with the F(ab')2 fragment of antimouse IgG. Response times were significantly faster for Fc gamma RII than for Fc gamma RIII. Peak concentrations of intracellular calcium ions after neutrophil stimulation were comparable for Fc gamma RII and RIII in healthy subjects. Neutrophils in patients with ankylosing spondylitis and osteoarthritis responded to Fc gamma R triggering, but in the group with active RA fluxes of calcium ions were severely depressed. Neutrophils isolated from patients with RA with quiescent disease showed exaggerated responses when compared with controls. Expression of all three Fc gamma R types on neutrophils from patients with active RA, as measured by monoclonal antibody binding, was comparable with control cells. Impairment of neutrophil Fc gamma R cytosolic signalling in active RA could reflect a receptor signalling defect with potential effects on Fc mediated functions, or a fundamental defect in calcium ion homeostasis within these cells. PMID:1535494

The effect of respiratory exercise on trunk control, pulmonary function, and trunk muscle activity in chronic stroke patients.

PubMed

Lee, Dong-Kyu; Kim, Se-Hun

2018-05-01

[Purpose] This study aims to identify the effect of respiratory exercise on trunk control, pulmonary function, and trunk muscle activity in chronic stroke patients. [Subjects and Methods] The study included 24 chronic stroke patients who were randomly assigned, 12 each, to the experimental and control groups, and received neurodevelopmental treatment. Moreover, the experimental group underwent respiratory exercise. In each patient, the trunk control was measured using the Trunk Impairment Scale (TIS); muscle activity of the trunk, through the surface electromyogram; and pulmonary function, using the pneumatometer. [Results] The intragroup comparison showed significant differences in TIS, Forced vital capacity (FVC), Forced expiratory volume at one second (FEV1), Rectus Abdominis (RA), Internal Oblique (IO) and External Oblique (EO) in the experimental group. The intergroup comparison showed that the differences in TIS, FVC, FEV1, RA, IO and EO within the experimental group appeared significant relative to the control group. [Conclusion] Based on these results, this study proved that respiratory exercise was effective in improving trunk control, pulmonary function, and trunk muscle activity in patients with chronic stroke.

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

PubMed

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

PubMed

Naranjo, A; Toloza, S; Guimaraes da Silveira, I; Lazovskis, J; Hetland, M L; Hamoud, H; Peets, T; Mäkinen, H; Gossec, L; Herborn, G; Skopouli, F N; Rojkovich, B; Aggarwal, A; Minnock, P; Cazzato, M; Yamanaka, H; Oyoo, O; Rexhepi, S; Andersone, D; Baranauskaite, A; Hajjaj-Hassouni, N; Jacobs, J W G; Haugeberg, G; Sierakowski, S; Ionescu, R; Karateew, D; Dimic, A; Henrohn, D; Gogus, F; Badsha, H; Choy, E; Bergman, M; Sokka, T

2010-01-01

To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Recommendations and the state of the evidence for physical activity interventions for adults with rheumatoid arthritis: 2007 to present

PubMed Central

Iversen, Maura D; Brawerman, Marisa; Iversen, Christina N

2013-01-01

Patients with rheumatoid arthritis (RA) are twice as likely as their healthy peers to suffer from cardiovascular disease. RA is also a major cause of disability and reduced quality of life. Clinical trials of exercise and physical activity interventions demonstrate positive effects on muscle strength, function, aerobic capacity, mood and disability. While RA management guidelines emphasize the role of exercise and physical activity in the management of RA, the description of physical activity and exercise is vague and patients with RA remain less physically active than their healthy counterparts. This review discusses the benefits of physical activity and current physical activity recommendations in RA, describes measurement techniques to assess physical activity, and synthesizes the data from interventions to promote physical activity and improve health outcomes in adults with RA. PMID:23538738

IL2RA Allele Increases Risk of Neuromyelitis Optica in Southern Han Chinese.

PubMed

Dai, Yongqiang; Li, Jin; Zhong, Xiaonan; Wang, Yuge; Qiu, Wei; Lu, Zhengqi; Wu, Aimin; Bao, Jian; Peng, Fuhua; Hu, Xueqiang

2013-11-01

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients. Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing. The rs2104286(G) frequency in the IL2RA gene was significantly higher in NMO patients than in controls (p(uncorr)=0.013, p(corr)=0.026, OR:1.942, 95%CI:1.146-3.291). The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population. Les allèles IL2RA augmentent le risque de neuromyélite optique chez les Chinois Han du sud.

Use of exploratory factor analysis to ascertain the correlation between the activities of rheumatoid arthritis and infection by human parvovirus B19.

PubMed

Kakurina, Natalja; Kadisa, Anda; Lejnieks, Aivars; Mikazane, Helena; Kozireva, Svetlana; Murovska, Modra

2015-01-01

We evaluated a possible correlation between the clinical activities of rheumatoid arthritis (RA) and human parvovirus B19 (B19) infection using exploratory factor analysis (EFA). RA patients were organized into two groups: 100 patients in the main group and 97 in the RA(DAS28) group. Four subgroups were defined from the main group according to the presence or absence of certain infection-specific markers: group I comprised 43 patients who had IgG antibodies against B19; group II, 25 patients with active B19 infection (B19-specific IgM antibodies and/or plasma viremia); group III, 19 patients with latent/persistent B19 infection (virus-specific sequences in peripheral blood leukocytes' DNA with or without B19-specific IgG antibodies), and group IV, 13 patients without infection markers. The RA(DAS28) group was divided into four subgroups similarly to the main group: group I, 35; group II, 31; group III, 19; and group IV, 12 patients. Disease-specific clinical values in both groups were analyzed employing EFA, and the RA(DAS28) group was additionally assessed using Disease Activity Score (DAS)28. RA activity was higher in patients who had markers of B19 infection. The highest activity of RA in both study groups was in patients with latent/persistent infection. In the RA(DAS28) group, according to DAS28, the highest activity of RA was in patients with active B19 infection. Using EFA and DAS28, a correlation between the clinical activity of RA and B19 infection was confirmed. These data suggest that EFA is applicable for medico-biological studies. Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Successful extension of tocilizumab infusion intervals from 4 weeks to 6 or 5 weeks in 90% of RA patients with good response to 4-week intervals.

PubMed

Saiki, Osamu; Uda, Hiroshi

2017-01-01

A period of 4 weeks (w) has been recommended as the interval between tocilizumab (TCZ) infusions for rheumatoid arthritis (RA). However, treating the patients with TCZ (8 mg/kg), we experienced that longer intervals were also effective. We conducted the study to investigate whether the intervals of TCZ infusions could extend from 4w to 5 or 6w. This was a retrospective observational study. RA patients who had shown good response to TCZ infusions at 4w intervals were enrolled, and the intervals of TCZ infusions were extended to 5w. Next, the intervals of TCZ infusion were extended to 6w for the patients who had maintained good response with 5w intervals. The patients who had maintained good response for more than two years were estimated as responders. One hundred patients were enrolled in the present study, and 62 patients maintained good response with 6w-interval infusions, and 28 patients with 5w-interval infusions, indicating that 90% of patients who had shown good response with 4w intervals could extend the intervals from 4w to 5 or 6w. The present study provides evidence that most of RA patients who showed good response to TCZ infusions at 4w could extend the intervals to 6w or 5w. This finding should be of great interest for both financial and labour reasons.

Assessment of activity limitations with the health assessment questionnaire predicts the need for support measures in patients with rheumatoid arthritis: a multicenter observational study.

PubMed

Janssens, Xavier; Decuman, Saskia; De Keyser, Filip

2014-01-01

This study investigated whether the Health Assessment Questionnaire (HAQ) can be used as an instrument to assess the need for social support measures that address activity limitations and participation issues in patients with rheumatoid arthritis (RA). This multicenter observational study included patients with RA and disease duration of at least one year, consulting their rheumatologist for routine evaluation of disease activity. In the single study visit data on demographics, disease history and current treatment were collected. DAS28 values were collected to evaluate current RA disease activity. Patients were asked to fill out the HAQ and SF-36 questionnaires. Receiver Operator Characteristics (ROC) curves were constructed to evaluate the performance of the HAQ, SF-36 and DAS28 in predicting the need for nine supporting measures available for chronically ill patients in the Belgian social security system. The expert opinion of the treating rheumatologist was used as a reference. The study included 316 patients with a mean age of 59.8 ± 12.6 years, disease duration of 11.4 ± 9.3 years, mean DAS28 values of 2.83 ± 1.17. Mean HAQ score was 0.95 ± 0.73, mean SF-36 score 56.5 ± 21.3. HAQ scores >1 were observed in 39.4% of patients. The area under the HAQ ROC curve was consistently >0.7 and higher for the HAQ than for SF-36 or DAS28 for all support measures. Rheumatologists on average recommended 3.67 support measures. The HAQ score was found to be a good predictor of the need for social support measures in patients with RA.

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease

PubMed Central

Canavan, James B; Scottà, Cristiano; Vossenkämper, Anna; Goldberg, Rimma; Elder, Matthew J; Shoval, Irit; Marks, Ellen; Stolarczyk, Emilie; Lo, Jonathan W; Powell, Nick; Fazekasova, Henrieta; Irving, Peter M; Sanderson, Jeremy D; Howard, Jane K; Yagel, Simcha; Afzali, Behdad; MacDonald, Thomas T; Hernandez-Fuentes, Maria P; Shpigel, Nahum Y; Lombardi, Giovanna; Lord, Graham M

2016-01-01

Background and aim Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn's blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown. Methods To define the optimum population for Treg cell therapy in CD, CD4+CD25+CD127loCD45RA+ and CD4+CD25+CD127loCD45RA− Treg subsets were isolated from patients’ blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. Results Tregs can be expanded from the blood of patients with CD to potential target dose within 22–24 days. Expanded CD45RA+ Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA− Tregs. CD45RA+ Tregs highly express α4β7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA+ Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA+ Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa. Conclusions CD4+CD25+CD127loCD45RA+ Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials. PMID:25715355

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

PubMed

Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis.

PubMed

Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Nikitenkiene, Rita; Jancoriene, Ligita; Mauricas, Mykolas; Nora-Krukle, Zaiga; Murovska, Modra; Girkontaite, Irute

2016-12-01

The present study aims to clarify the possible involvement of parvovirus B19 (B19V) infection in rheumatoid arthritis (RA) pathogenesis by investigating the presence of B19V infection markers (genomic sequences and virus-specific antibodies) in association with the level of cytokines and RA clinical activity and aggressiveness. A total of 118 RA patients and 49 age- and sex-matched healthy volunteers were enrolled in the study. Nested PCR was used to detect B19V sequences in whole blood and cell-free plasma DNA, ELISA to detect virus-specific antibodies and cytokine levels in plasma and recomLine dot blot assay for antibodies to separate B19V antigens. The detection frequency of B19V DNA was higher in patients with RA (25.4 %) in comparison with healthy persons (18.4 %). B19V DNA in cell-free plasma (B19+p) was detected significantly often in RA patients in comparison with healthy controls (13.6 vs 2 %; P=0.0002). RA B19+p patients had higher disease activity and aggressiveness, decreased haemoglobin and increased erythrocyte sedimentation rates. IL-6 plasma levels were significantly higher in RA patients than in controls. Within the RA patients' group the IL-6 level was significantly increased in B19+p patients with disease activity scores of DAS28>5.2, high C-reactive protein and low haemoglobin. Contrary to the healthy controls, the majority of RA B19+p patients did not have antibodies to VP-1S (VP1u) and VP-N (N-terminal half of structural proteins VP1 and VP2), which correspond to the epitopes of neutralizing antibodies. These results indicate that B19V infection at least in some patients is involved in RA pathogenesis.

An easy method for Ra-226 determination in river waters by liquid-scintillation counting

NASA Astrophysics Data System (ADS)

Moreno, H. P.; Vioque, I.; Manjón, G.; García-Tenorio, R.

1999-01-01

226Ra activity concentration in river water was determined using a low background liquid scintillation counter. Radium was extracted from the samples as Ra-BaSO4 precipitate which, afterwards, was dissolved with EDTA in ammonia medium. Solution was transferred into a low potassium glass vial and then mixed with a scintillation cocktail. Two different scintillation cocktails were selected for comparison. Efficiency, recovery yield and α/β separation were studied with both liquid scintillation cocktails. One single measurement, made one month after radium separation, allows to calculate the226Ra concentration as well as to assess the presence of alpha contamination of the sample. In the case of negligible interferences,224Ra concentrations can be subsequently evaluated in the same sample by the measurement made just after chemical separation of radium. This method has been applied for the determination of226Ra and224Ra activity concentrations in river water collected from different locations along the Odiel river estuary area (South-west of Spain). The presence of chemical industry, the wastes of which are released into the river, could be connected with radium activity concentration enhancements in the water.

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

PubMed

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

CD4+ CD25+ CD127low Regulatory T Cells as Indicator of Rheumatoid Arthritis Disease Activity.

PubMed

Khattab, Sahar S; El-Saied, Amany M; Mohammed, Rehab A; Mohamed, Eman E

2016-06-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by disturbed immune regulation, inducing a progressive cartilage and bone destruction. Despite enrichment of T regulatory cell (T-regs) in synovial fluid, conflicting results are reported concerning T-regs in peripheral blood (PB) of RA patients. To determine possible correlation between the frequency of PB CD4+ CD25+CD127low (T-regs) with RA disease activity. Forty females with RA, classified according to the Disease Activity Score 28 (DAS-28), as highly active, mild-moderate or low disease activity; and 20 age and sex matched healthy controls, were enrolled to study CD4+ CD25+ CD127low T- regs in PB by flow cytometry. Active RA patients had lower frequency of the CD4+ CD25+ CD127low T- regs compared to those with mild-moderate or low disease activity (P <0.001). The frequencies of the T- regs showed negative correlation with the DAS-28 (P<0.01). In conclusion, CD4+ CD25+ CD127low T-regs is significantly lower in highly active RA patients compared to patients with lower activity or controls. Copyright© by the Egyptian Association of Immunologists.

Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

PubMed

Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

2015-01-01

The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture. Copyright © 2014 Elsevier Ltd. All rights reserved.

Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis

PubMed Central

Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Nikitenkiene, Rita; Jancoriene, Ligita; Mauricas, Mykolas; Nora-Krukle, Zaiga; Murovska, Modra

2016-01-01

The present study aims to clarify the possible involvement of parvovirus B19 (B19V) infection in rheumatoid arthritis (RA) pathogenesis by investigating the presence of B19V infection markers (genomic sequences and virus-specific antibodies) in association with the level of cytokines and RA clinical activity and aggressiveness. A total of 118 RA patients and 49 age- and sex-matched healthy volunteers were enrolled in the study. Nested PCR was used to detect B19V sequences in whole blood and cell-free plasma DNA, ELISA to detect virus-specific antibodies and cytokine levels in plasma and recomLine dot blot assay for antibodies to separate B19V antigens. The detection frequency of B19V DNA was higher in patients with RA (25.4 %) in comparison with healthy persons (18.4 %). B19V DNA in cell-free plasma (B19+p) was detected significantly often in RA patients in comparison with healthy controls (13.6 vs 2 %; P=0.0002). RA B19+p patients had higher disease activity and aggressiveness, decreased haemoglobin and increased erythrocyte sedimentation rates. IL-6 plasma levels were significantly higher in RA patients than in controls. Within the RA patients’ group the IL-6 level was significantly increased in B19+p patients with disease activity scores of DAS28>5.2, high C-reactive protein and low haemoglobin. Contrary to the healthy controls, the majority of RA B19+p patients did not have antibodies to VP-1S (VP1u) and VP-N (N-terminal half of structural proteins VP1 and VP2), which correspond to the epitopes of neutralizing antibodies. These results indicate that B19V infection at least in some patients is involved in RA pathogenesis. PMID:27902343

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

PubMed

Jiménez-Sousa, María Ángeles; Gómez-Moreno, Ana Zaida; Pineda-Tenor, Daniel; Medrano, Luz Maria; Sánchez-Ruano, Juan José; Fernández-Rodríguez, Amanda; Artaza-Varasa, Tomas; Saura-Montalbán, José; Vázquez-Morón, Sonia; Ryan, Pablo; Resino, Salvador

2018-01-01

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

PubMed

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

Fibromyalgia remains a significant burden in rheumatoid arthritis patients in Australia.

PubMed

Gist, Anthea C; Guymer, Emma K; Eades, Laura E; Leech, Michelle; Littlejohn, Geoffrey O

2018-03-01

High rates of fibromyalgia (FM) are reported in rheumatoid arthritis (RA) patients. Advances in RA management have occurred, but information regarding current significance of FM in RA is limited. This investigation estimated the prevalence and health effects of concomitant FM in Australian RA patients. Participants were recruited from Australian rheumatology clinics. Subjects were assessed using the 1990 and 2011 American College of Rheumatology (ACR) FM criteria and the polysymptomatic distress score (PDS) was calculated. A medical history and a clinical examination were recorded. RA Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS-28 ESR), and the Short Form-36 survey (SF-36) were completed. Of 117 RA patients, 33.3% (n = 39) met 1990 ACR FM criteria and 41.9% (n = 49) met 2011 ACR FM criteria. RA patients with comorbid FM had worse outcomes across all domains of health as defined by the SF-36 (P < 0.05). There was correlation between both physical and mental health outcomes and the PDS (P < 0.001). RA patients with FM on average took 1.18 extra ongoing prescribed medications (P < 0.05), despite comparable RA disease activity (DAS-28: 3.09 vs. 3.27, P = NS). Comorbid central sensitivity conditions were more common in patients with FM (P < 0.001). FM continues to demonstrate a high prevalence in a population of RA patients. RA patients with FM have more symptoms of other chronic sensitivity syndromes in addition to FM. They have a lower quality of life outcome and higher medication use. This has important clinical implications in terms of diagnosis, response to therapy, prescribing choices and clinical outcomes. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis.

PubMed

Rannio, Tuomas; Asikainen, Juha; Kokko, Arto; Hannonen, Pekka; Sokka, Tuulikki

2016-04-01

We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

[Anti-rheumatic therapy in patients with rheumatoid arthritis undergoing hemodialysis].

PubMed

Akiyama, Yuji

2011-01-01

Hemodialysis (HD) patients have been increasing recently. Some rheumatoid arthritis (RA) patients need hemodialysis (HD), though the proportion is not high. At present, such patients are almost treated with corticosteroids and/or nonsteroidal anti-inflammatory drugs alone, even if they have a high disease activity that would require disease-modifying anti-rheumatic drug (DMARD) therapy, partly because the safety of DMARDs in RA patients with end-stage renal disease has not been confirmed. Their joint destruction would be inevitable and lead to impaired activities of daily living. As there are no guidelines for the use of DMARDs in HD patients, here I reviewed the previous reports about the treatment of DMARDs including biologics for patients with RA undergoing HD.

Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.

PubMed

Carr, Edward J; Clatworthy, Menna R; Lowe, Christopher E; Todd, John A; Wong, Andrew; Vyse, Timothy J; Kamesh, Lavanya; Watts, Richard A; Lyons, Paul A; Smith, Kenneth G C

2009-03-05

Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D. We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV. We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease.

CD45RA, a specific marker for leukaemia stem cell sub-populations in acute myeloid leukaemia.

PubMed

Kersten, Bas; Valkering, Matthijs; Wouters, Rolf; van Amerongen, Rosa; Hanekamp, Diana; Kwidama, Zinia; Valk, Peter; Ossenkoppele, Gert; Zeijlemaker, Wendelien; Kaspers, Gertjan; Cloos, Jacqueline; Schuurhuis, Gerrit J

2016-04-01

Chemotherapy resistant leukaemic stem cells (LSC) are thought to be responsible for relapses after therapy in acute myeloid leukaemia (AML). Flow cytometry can discriminate CD34(+) CD38(-) LSC and normal haematopoietic stem cells (HSC) by using aberrant expression of markers and scatter properties. However, not all LSC can be identified using currently available markers, so new markers are needed. CD45RA is expressed on leukaemic cells in the majority of AML patients. We investigated the potency of CD45RA to specifically identify LSC and HSC and improve LSC quantification. Compared to our best other markers (CLL-1, also termed CLEC12A, CD33 and CD123), CD45RA was the most reliable marker. Patients with high percentages (>90%) of CD45RA on CD34(+) CD38(-) LSC have 1·69-fold higher scatter values compared to HSC (P < 0·001), indicating a more mature CD34(+) CD38(-) phenotype. Patients with low (<10%) or intermediate (10-90%) CD45RA expression on LSC showed no significant differences to HSC (1·12- and 1·15-fold higher, P = 0·31 and P = 0·44, respectively). CD45RA-positive LSC tended to represent more favourable cytogenetic/molecular markers. In conclusion, CD45RA contributes to more accurate LSC detection and is recommended for inclusion in stem cell tracking panels. CD45RA may contribute to define new LSC-specific therapies and to monitor effects of anti-LSC treatment. © 2016 John Wiley & Sons Ltd.

Reevaluation of the role of duration of morning stiffness in the assessment of rheumatoid arthritis activity.

PubMed

Khan, Nasim A; Yazici, Yusuf; Calvo-Alen, Jaime; Dadoniene, Jolanta; Gossec, Laure; Hansen, Troels M; Huisman, Margriet; Kallikorm, Riina; Muller, Raili; Liveborn, Margareth; Oding, Rolf; Luchikhina, Elena; Naranjo, Antonio; Rexhepi, Sylejman; Taylor, Peter; Tlustochowich, Witold; Tsirogianni, Afrodite; Sokka, Tuulikki

2009-11-01

To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 RA. Mixed-effect analysis of covariance (ANCOVA) models were used to assess the utility of adding MS duration to Routine Assessment of Patient Index Data (RAPID)3, a PRO index based on physical function, pain, and general health (GH), in predicting the 3-variable DAS28 (DAS28v3). MS duration had moderate correlation (r = 0.41-0.48) with pain, Health Assessment Questionnaire, and GH; and weak correlation (r = 0.23-0.39) with joint counts and erythrocyte sedimentation rate. MS duration differed significantly among patients with different RA activity (p < 0.001). The area under the ROC curve of 0.74 (95% CI 0.72-0.75) showed moderate ability of MS duration to differentiate clinically active from less active RA. ANCOVA showed significant interactive effects between RAPID3 and the MS duration categories (p = 0.0005) in predicting DAS28v3. The effect of MS was found to be clinically important in patients with the low RAPID3 scores (< 6) in whom the presence of MS may indicate clinically active disease (DAS28v3 > 3.2). MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

Evaluation of Real-World Experience with Tofacitinib Compared with Adalimumab, Etanercept, and Abatacept in RA Patients with 1 Previous Biologic DMARD: Data from a U.S. Administrative Claims Database.

PubMed

Harnett, James; Gerber, Robert; Gruben, David; Koenig, Andrew S; Chen, Connie

2016-12-01

Real-world data comparing tofacitinib with biologic disease-modifying antirheumatic drugs (bDMARDs) are limited. To compare characteristics, treatment patterns, and costs of patients with rheumatoid arthritis (RA) receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA], etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S. administrative claims database. This study was a retrospective cohort analysis of patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM codes 714.0x-714.4x; 714.81) and 1 previous bDMARD filling ≥ 1 tofacitinib or bDMARD claim in the Truven MarketScan Commercial and Medicare Supplemental claims databases (November 1, 2012-October 31, 2014). Monotherapy was defined as absence of conventional synthetic DMARDs within 90 days post-index. Persistence was evaluated using a 60-day gap. Adherence was assessed using proportion of days covered (PDC). RA-related total, pharmacy, and medical costs were evaluated in the 12-month pre- and post-index periods. Treatment patterns and costs were adjusted using linear models including a common set of clinically relevant variables of interest (e.g., previous RA treatments), which were assessed separately using t-tests and chi-squared tests. Overall, 392 patients initiated tofacitinib; 178 patients initiated ADA; 118 patients initiated ETN; and 191 patients initiated ABA. Tofacitinib patients were older versus ADA patients (P = 0.0153) and had a lower proportion of Medicare supplemental patients versus ABA patients (P = 0.0095). Twelve-month pre-index bDMARD use was greater in tofacitinib patients (77.6%) versus bDMARD cohorts (47.6%-59.6%). Tofacitinib patients had greater 12-month pre-index RA-related total costs versus bDMARD cohorts (all P < 0.0001) and greatest index use of monotherapy (P = 0.0080 vs. ABA). A similar (all P > 0.10) proportion of patients were persistent with tofacitinib (42.6%) versus ADA (37.6%), ETN (42.4%), and ABA (43.5%). Mean PDC was 0.55 for

RA190, a Proteasome Subunit ADRM1 Inhibitor, Suppresses Intrahepatic Cholangiocarcinoma by Inducing NF-KB-Mediated Cell Apoptosis.

PubMed

Yu, Guang-Yang; Wang, Xuan; Zheng, Su-Su; Gao, Xiao-Mei; Jia, Qing-An; Zhu, Wen-Wei; Lu, Lu; Jia, Hu-Liang; Chen, Jin-Hong; Dong, Qiong-Zhu; Lu, Ming; Qin, Lun-Xiu

2018-06-15

Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays. The effects of RA190 on the proliferation and survival of both established ICC cell lines and primary ICC cells were examined in vitro. Annexin V/propidium iodide staining, western blotting and immunohistochemical staining were performed. The in vivo anti-tumor effect of RA190 on ICC was validated in subcutaneous xenograft and patient-derived xenograft (PDX) models. ADRM1 levels were significantly higher in ICC tissues than in normal bile duct tissues. ICC patients with high ADRM1 levels had worse overall survival (hazard ratio [HR] = 2.383, 95% confidence interval [CI] =1.357 to 4.188) and recurrence-free survival (HR = 1.710, 95% CI =1.045 to 2.796). ADRM1 knockdown significantly inhibited ICC growth in vitro and in vivo. The specific inhibitor RA190 targeting ADRM1 suppressed proliferation and reduced cell vitality of ICC cell lines and primary ICC cells significantly in vitro. Furthermore, RA190 significantly inhibited the proteasome by inactivating ADRM1, and the consequent accumulation of ADRM1 substrates decreased the activating levels of NF-κB to aggravate cell apoptosis. The therapeutic benefits of RA190 treatment were further demonstrated in both subcutaneous implantation and PDX models. Our findings indicate that up-regulated ADRM1 was involved in ICC progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment. �

Origin and transport of (238)U and (226)Ra in riverine, estuarine and marine sediments of the Krka River, Croatia.

PubMed

Cukrov, Neven; Mlakar, Marina; Cuculić, Vlado; Barisić, Delko

2009-06-01

Spatial distribution of (238)U and (226)Ra activities in sediment columns along the Krka River and estuary, were studied using gamma spectrometry. Markedly different (238)U and (226)Ra activities between riverine, estuarine and marine sediments were observed. Distribution of these radionuclides, as well as their anthropogenic and natural origin, was evaluated by activity measurements, taking into account sedimentation rates estimated by (137)Cs distribution in sediment columns. Naturally present (238)U and (226)Ra activities were highest in riverine and lowest in marine sediments. (238)U and (226)Ra activities in historic riverine sediments revealed anthropogenic influence from town of Knin, which diminished for 15-20% in 1990s due to warfare that caused stop of industrial, agricultural and transport activities. Drainage of the flysch material naturally elevates (238)U and (226)Ra activities in the vicinity of its inflow in the upper part of estuary. (238)U and (226)Ra from the phosphate ore discharge in the port of Sibenik did not spread further in estuary, which was also confirmed by (238)U and (226)Ra activities detected in Mytilus sp. mussels' tissue.

Perceptions of physical activity engagement among adults with rheumatoid arthritis and rheumatologists.

PubMed

Iversen, Maura D; Scanlon, Lauren; Frits, Michelle; Shadick, Nancy A; Sharby, Nancy

Physical activity (PA) among adults with rheumatoid arthritis (RA) is suboptimal. This study assessed PA motivations and perceptions in adults with RA and rheumatologists. Patients and rheumatologists participated in structured interviews led by a behavioral scientist. Sessions were audiotaped, transcribed and coded. Twenty-three patients (mean age = 63 [standard deviation = 10], 96% female) and seven rheumatologists (57% male, 29% fellows) participated. Nine themes emerged: communication with the rheumatologist, environment/access, symptom management, social support, mental health, breaking inactivity cycles, integrating PA into routines, staying in control and challenge/intimidation. Highly active patients viewed PA differently than low active patients. The need to compete with RA-free individuals may impede PA. Understanding how patients conceptualize PA will enable clinicians to formulate PA strategies to motivate patients.

The association of immunoglobulin A, immunoglobulin G and anti-cyclic citrullinated peptide antibodies with disease activity in seronegative rheumatoid arthritis patients.

PubMed

Karimifar, Mansoor; Moussavi, Hamidreza; Babaei, Mehran; Akbari, Mojtaba

2014-09-01

Rheumatoid arthritis (RA) is a common autoimmune disease that is associated with progressive disability, systemic complications, and early death. The present study was aimed to investigate the level of immunoglobulin G (IgG) and IgA isotypes and anti-cyclic citrullinated peptide (CCP) antibody and to assess their association with disease severity based on disease activity score (DAS-28) in patients with IgM rheumatoid factor (IgM-RF) negative RA. In this cross-sectional study, 62 RA patients with IgM-RF negative were assessed. Radiographs were obtained for all RA patients. The RF (IgG, and IgA) and anti-CCP were measured by using the enzyme-linked immunosorbent assay. Values of cut-off points over 15 UI/mL for IgA IgA-RF, 20 UI/mL for IgG-RF and over 20 units for anti-CCP were considered positive. DAS-28 score was compared in regard to the IgA-RF and IgG-RF and anti-CCP positivity using Mann-Whitney test. DAS-28 score in IgA-RF positive was significantly higher than IgA-RF negative (mean score, 6.03 ± 0.33 vs. 5.44 ± 0.76 respectively, P = 0.035). In IgG-RF positive patients, DAS-28 score was similar to patients with IgG-RF negative (5.64 ± 0.59 vs. 5.46 ± 0.78 respectively, P = 0.396). Furthermore, in patients with anti-CCP positive DAS-28 score was significantly higher than patients with anti-CCP negative (5.72 ± 0.61 vs. 5.38 ± 0.79 respectively, P = 0.049). Findings indicated that there was a significant association between the amounts of IgA and anti-CCP with severity of disease in RF negative RA patients while there was no significant association between the amounts of IgG and severity of RA disease.

Sleep quality in fibromyalgia and rheumatoid arthritis: associations with pain, fatigue, depression, and disease activity.

PubMed

Ulus, Y; Akyol, Y; Tander, B; Durmus, D; Bilgici, A; Kuru, O

2011-01-01

The aim of this study was to compare the sleep quality in patients with rheumatoid arthritis (RA) and fibromyalgia syndrome (FMS); and to evaluate the relationship between sleep quality and pain, fatigue, depression, and disease activity in patients with RA and FMS. Forty RA, 40 FMS and 40 healthy controls were enrolled in the study. Disease activity and disease duration were reported in patients. Pain by visual analogue scale (VAS), fatigue by Multidimensional Assesment of Fatigue (MAF), depression by Beck Depression Index (BDI), and sleep quality by Pittsburgh Sleep Quality Index (PSQI) were gathered in all participants. All participants were aged between 20 and 65 years, with a mean age of 42.97±10.75 years. There was no significant difference with respect to demographic characteristics among the three study groups. Patients reported more depression than controls, but BDI scores were similar in FMS and RA patients. VAS pain scores and MAF scores were significantly different in the three groups (p<0.001). FMS and RA patients had poor sleep quality (p<0.001). FMS patients had daytime dysfunction due to sleep disorder and had worse habitual sleep efficiency than RA patients (p<0.05). In patients, positive correlations were found between PSQI and clinic assessment variables except disease duration. FMS and RA may have poor sleep quality when compared to subjects without rheumatologic disorders. The quality of sleep can be impaired by pain, fatigue, depression, and disease activity in such patients.

Frequency-dependent response of SI RA-class neurons to vibrotactile stimulation of the receptive field.

PubMed

Whitsel, B L; Kelly, E F; Xu, M; Tommerdahl, M; Quibrera, M

2001-01-01

Three types of experiment were carried out on anesthetized monkeys and cats. In the first, spike discharge activity of rapidly adapting (RA) SI neurons was recorded extracellularly during the application of different frequencies of vibrotactile stimulation to the receptive field (RF). The second used the same stimulus conditions to study the response of RA-I (RA) cutaneous mechanoreceptive afferents. The third used optical intrinsic signal (OIS) imaging and extracellular neurophysiological recording methods together, in the same sessions, to evaluate the relationship between the SI optical and RA neuron spike train responses to low- vs high-frequency stimulation of the same skin site. RA afferent entrainment was high at all frequencies of stimulation. In contrast, SI RA neuron entrainment was much lower on average, and was strongly frequency-dependent, declining in near-linear fashion from 6 to 200 Hz. Even at 200 Hz, however, unambiguous frequency-following responses were present in the spike train activity of som

Characteristics of hand involvement in a comparative study of two early RA cohorts from the UK and China.

PubMed

Su, Bowen; Ma, Qing; Edwards, Christopher J; Williams, Mark; Adams, Jo

2017-10-01

To compare the characteristics of early hand involvement in rheumatoid arthritis (RA) using two matched populations, from the UK and China. A cohort comparison study was conducted. Sixty Chinese patients recruited from Shanghai, China were matched on gender and age with 60 patients from a prospective early RA cohort from the UK (SARAH trial). The procedures of data collection in China followed the standard operating procedures employed in the SARAH trial. Outcome measures including Michigan Hand Outcomes Questionnaire (MHQ), medication history and physical assessments were used to assess functional ability and hand impairment. UK patients reported significantly more hand pain (P = 0.015), less satisfaction with dominant hand performance (P  = 0.040), more swollen and tender joints (P = 0.016 and P = 0.001) and greater dexterity of both dominant and non-dominant hands (P < 0.001 and P < 0.001), while Chinese patients had higher disease activity indicated by erythrocyte sedimentation rate and C-reactive protein, more rheumatoid factor, less satisfaction in both dominant and non-dominant hand appearances (P < 0.001 and P < 0.001, respectively) and greater dominant hand deformity (P  = 0.003). No statistically significant differences were seen in range of movement and overall hand function as reported by the MHQ. The severity of RA is not milder in China than in the UK and the characteristics of hand involvement tend to be different. Clinicians should consider country-specific differences in managing pain and delivering treatment. It would be helpful for a future study to investigate the RA impact characteristics on a wider range of patients both from within China and from other populations. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Role of hydrotherapy in the amelioration of oxidant-antioxidant status in rheumatoid arthritis patients.

PubMed

Mateen, Somaiya; Moin, Shagufta; Khan, Abdul Q; Zafar, Atif; Fatima, Naureen; Shahzad, Sumayya

2017-06-14

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Reactive oxygen species (ROS) are involved in the pathophysiology of RA. Moderate intensity exercises have been reported to have anti-oxidant and anti-inflammatory effects. The aim of this study was to evaluate the effect of hydrotherapy on oxidant-antioxidant status in RA patients. Forty RA patients and 30 age- and sex-matched healthy controls were included in this study. RA patients were subdivided into two groups: the first group (n = 20) received treatment with conventional RA drugs, while the second group (n = 20) received hydrotherapy along with the conventional drugs for a period of 12 weeks. Disease Activity Score of 28 joints (DAS-28), ROS level, protein oxidation, lipid peroxidation, DNA damage and the activities of antioxidant enzymes were evaluated before and after 12 weeks of treatment. RA patients showed a significant change in the oxidative stress biomarkers (ROS, P < 0.01; ferric reducing antioxidant potential, P < 0.001; malondialdehyde, P < 0.01; protein carbonyl, P < 0.001; tail length, P < 0.05) and decrease in the activities of anti-oxidant enzymes (superoxide dismutase [SOD], P < 0.01; glutathione peroxidase [GPx], P < 0.001). Conventional drug treatment has not produced any significant change in these parameters. However, cotreatment of drugs with hydrotherapy has decreased protein, lipid and DNA oxidation by increasing the activities of antioxidant enzymes (SOD and GPx). Our results indicate that hydrotherapy along with drugs has reduced the severity of disease (DAS-28) by ameliorating the oxidant-antioxidant status in RA patients. Thus, in addition to conventional drugs, RA patients should be advised to have hydrotherapy (moderate intensity exercise) in their treatment regimen. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de; Riesner, Anica; Jahn, Patrick

Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in thismore » period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.« less

Behaviors of 323Th, 238U, 228Ra and 226Ra on combustion of crude oil terminal sludge.

PubMed

Puad, H A Mohamad; Noor, M Y Muhd

2004-01-01

Crude oil terminal sludge contains technologically enhanced naturally occurring radionuclides such as (232)Th, (238)U, (228)Ra and (226)Ra, thus cannot be disposed of freely without proper control. The current method of disposal, such as land farming and storing in plastic drums is not recommended because it will have a long-term impact on the environment. Due to its organic nature, there is a move to treat this sludge by thermal methods such as incineration. This study has been carried out to determine the behaviors of (232)Th, (238)U, (228)Ra and (226)Ra present in the sludge during combustion at a certain temperature and time. The percentage of volatilization was found to vary between 2% and 70%, (238)U was the most volatile in comparison with (232)Th, (228)Ra and (226)Ra. (238)U is found to be significantly volatilized above 500 degrees C, and might reach maximum volatilization at above 700 degrees C. A mathematical model was developed to predict the percentage of volatilization of (232)Th, (238)U, (228)Ra and (226)Ra contained in the sludge. With this known percentage of volatilization, the concentration of (232)Th, (238)U, (228)Ra and (226)Ra present in the bottom and filter ashes can be calculated.

Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis.

PubMed

Barbosa-Cobos, Rosa Elda; Lugo-Zamudio, Gustavo; Flores-Estrada, Javier; Becerril-Mendoza, Lizbeth Teresa; Rodríguez-Henríquez, Pedro; Torres-González, Rubén; Moreno-Eutimio, Mario Adán; Ramirez-Bello, Julian; Moreno, José

2018-04-01

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student's t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p < 0.0001). SP levels correlated with DAS28-CRP (r = 0.5050, p < 0.0001), number of tender joints (NTJ, r = 0.4668, p < 0.0001), number of swollen joints (NSJ, r = 0.4439, p < 0.0001), visual analogue scale (VAS, r = 0.5131, p < 0.0001). However, SP did not correlate with CRP levels (r = 0.0468, p = 0.6613), nor with the USPD (r = 0.1740, p = 0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.

Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis.

PubMed

Chen, J R; Takahashi, M; Suzuki, M; Kushida, K; Miyamoto, S; Inoue, T

1998-12-01

Pentosidine is an advanced glycation endproduct formed by glycosylation and oxidation. Our aim was to develop a means to measure pentosidine in synovial fluid (SF), and to compare its concentration in SF in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to investigate the relationship between its concentration in SF and the disease activity of RA. SF was collected from knee joints in 31 patients with RA and 40 with OA, who had hydrarthrosis. One patient with RA and 7 with OA who had the complication of diabetes mellitus or chronic renal failure made up the DM/CRF group, and the remaining patients made up the RA group (n = 30) and the OA group (n = 33). Pentosidine was measured by the direct HPLC method with column switching after hydrolysis of SF. Pentosidine was detected in all SF and was greater in RA (83.9 +/- 46.0 nmol/l, mean +/- SD) than in OA (40.1 +/- 19.6 nmol/l). Three DM/CRF patients undergoing hemodialysis had markedly high pentosidine levels (482.5 +/- 280.8 nmol/l). There was a significant correlation between pentosidine and C-reactive protein (CRP), erythrocyte sedimentation rate, and Lansbury Index (p < 0.01). Patients with RA were divided into high and low activity groups according to the CRP and Lansbury Index. Pentosidine was significantly higher in the high activity group (CRP > or = 2.0 mg/dl and Lansbury Index > or = 50%) than in the low activity group (CRP < 2.0 and/or Lansbury Index < 50) (100.9 +/- 42.8 vs 58.5 +/- 39.6 nmol/; p = 0.0013). Pentosidine in synovial fluid was higher in RA than in OA. Pentosidine levels in SF were related to the disease activity in RA.

PADI4 and HLA-DRB1 are genetic risks for radiographic progression in RA patients, independent of ACPA status: results from the IORRA cohort study.

PubMed

Suzuki, Taku; Ikari, Katsunori; Yano, Koichiro; Inoue, Eisuke; Toyama, Yoshiaki; Taniguchi, Atsuo; Yamanaka, Hisashi; Momohara, Shigeki

2013-01-01

Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease influenced by both genetic and environmental factors, leading to joint destruction and functional impairment. Recently, a large-scaled GWAS meta-analysis using more than 37,000 Japanese samples were conducted and 13 RA susceptibility loci were identified. However, it is not clear whether these loci have significant impact on joint destruction or not. This is the first study focused on the 13 loci to investigate independent genetic risk factors for radiographic progression in the first five years from onset of RA. Sharp/van der Heijde score of hands at 5-year disease duration, which represents joint damage, were measured retrospectively and used as an outcome variable in 865 Japanese RA patients. Genetic factors regarded as putative risk factors were RA-susceptible polymorphisms identified by the Japanese GWAS meta-analysis, including HLA-DRB1 (shared epitope, SE), rs2240340 (PADI4), rs2230926 (TNFAIP3), rs3093024 (CCR6), rs11900673 (B3GNT2), rs2867461 (ANXA3), rs657075 (CSF2), rs12529514 (CD83), rs2233434 (NFKBIE), rs10821944 (ARID5B), rs3781913 (PDE2A-ARAP1), rs2841277 (PLD4) and rs2847297 (PTPN2). These putative genetic risk factors were assessed by a stepwise multiple regression analysis adjusted for possible non-genetic risk factors: autoantibody positivity (anti-citrullinated peptide antibody [ACPA] and rheumatoid factor), history of smoking, gender and age at disease onset. The number of SE alleles (P = 0.002) and risk alleles of peptidyl arginine deiminase type IV gene (PADI4, P = 0.04) had significant impact on progressive joint destruction, as well as following non-genetic factors: ACPA positive (P = 0.0006), female sex (P = 0.006) and younger age of onset (P = 0.02). In the present study, we found that PADI4 risk allele and HLA-DRB1 shared epitope are independent genetic risks for radiographic progression in Japanese rheumatoid arthritis patients. The results of this

Activity concentration, transfer factors and resultant radiological risk of 226Ra, 232Th, and 40K in soil and some vegetables consumed in Selangor, Malaysia

NASA Astrophysics Data System (ADS)

Solehah, A. R.; Yasir, M. S.; Samat, S. B.

2016-11-01

The activity concentrations of the natural radionuclides 226Ra, 232Th, and 40K were determined in vegetable crops consumed by Malaysian people in Sungai Besar, Selangor. Sample of vegetables and the soil where the crops were cultivated and collected at five different location. The activity concentrations in Bq/kg of 226Ra, 232Th, and 40K were measured by the gamma-ray spectroscopy using the high purity germanium detector. The range activity concentration in soil is between 51.81 and 71.84 Bq/kg, 64.18 and 78.00 Bq/kg, and 210.49 and 244.29 Bq/kg for 226Ra, 232Th, and 40K, respectively. The activity concentration of 226Ra, 232Th, and 40K in vegetables were found to be in the range of 2.06 to 5.44 Bq/kg, Not Detectable to 0.61 Bq/kg, and 101.00 to 1223.09 Bq/kg, respectively. The activity concentration in both soil and vegetables were all less than lower limit stated by UNSCEAR. The Transfer Factors range value for 226Ra, 232Th, and 40K varied from 0.02 to 0.06, 0.003 to 0.008, and 1.79 to 5.19 respectively. Radium equivalent for soil range from 165.57 to 194.84 Bq/kg. It was within the international accepted value (370 Bq/kg). Absorb dose rate for soil range between 73.5 to 86.40 nGyh-1, in safe range from limit of international accepted value (55nGyh-1). Effective dose rate is found to be in range of 0.09 to 0.11 mSvy-1 for soil which is less than 2.4 mSv/y. External and Internal Hazard indices of soil was all below 1, within agreement of other researcher and UNSCEAR. The estimation of the consequent radiological risk due to the presence of those radionuclides is significantly low.

Anti-citrullinated protein antibodies contribute to platelet activation in rheumatoid arthritis.

PubMed

Habets, Kim L L; Trouw, Leendert A; Levarht, E W Nivine; Korporaal, Suzanne J A; Habets, Petra A M; de Groot, Philip; Huizinga, Tom W J; Toes, René E M

2015-08-24

Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis. We set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of anti-citrullinated protein antibodies (ACPA). Platelets from healthy controls were incubated in the presence of plasma of patients with RA or age- and sex-matched healthy controls and plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. Characteristics of platelets isolated from patients with RA were correlated to disease activity. Platelets isolated from healthy controls displayed markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of soluble CD40 ligand (sCD40L). Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titres. In accordance with these findings, enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Pre-incubation of platelets with blocking antibodies directed against low-affinity immunoglobulin G receptor (FcγRIIa) completely inhibited the ACPA-mediated activation. In addition, expression of P-selectin measured as number of platelets correlated with Disease Activity Score in 44 joints, C-reactive protein level, ACPA status and ACPA level. We show for the first time that ACPA can mediate an FcγRIIa-dependent activation of platelets. As ACPA can be detected several years before RA disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis onset.

A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment.

PubMed

Durez, P; Nzeusseu Toukap, A; Lauwerys, B R; Manicourt, D H; Verschueren, P; Westhovens, R; Devogelaer, J-P; Houssiau, F A

2004-09-01

To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6. Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (p<0.05). None of the QoL scales improved with MP treatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP. This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres.

PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.

PubMed

Crilly, A; Burns, E; Nickdel, M B; Lockhart, J C; Perry, M E; Ferrell, P W; Baxter, D; Dale, J; Dunning, L; Wilson, H; Nijjar, J S; Gracie, J A; Ferrell, W R; McInnes, I B

2012-06-01

Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Patients with RA had elevated but variable surface expression of PAR(2) on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86-4.10%) vs 0.06% (0.03-0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR(2) expression in patients with RA compared with controls (3.05% (0.36-11.82%) vs 0.08% (0.02-0.28%), p<0.0001). For both subsets, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR(2) expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR(2) expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). These findings are consistent with a pathogenic role for PAR(2) in RA.

PAR2 expression in peripheral blood monocytes of patients with rheumatoid arthritis

PubMed Central

Crilly, A; Burns, E; Nickdel, M B; Lockhart, J C; Perry, M E; Ferrell, P W; Baxter, D; Dale, J; Dunning, L; Wilson, H; Nijjar, J S; Gracie, J A; Ferrell, W R; McInnes, I B

2012-01-01

Objectives Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR2 expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Methods Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR2 on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Results Patients with RA had elevated but variable surface expression of PAR2 on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86–4.10%) vs 0.06% (0.03–0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR2 expression in patients with RA compared with controls (3.05% (0.36–11.82%) vs 0.08% (0.02–0.28%), p<0.0001). For both subsets, PAR2 expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR2 expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR2 expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR2 expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR2 agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). Conclusions These findings are consistent with a pathogenic role for PAR2 in RA. PMID:22294633

High-Speed RaPToRS

NASA Astrophysics Data System (ADS)

Henchen, Robert; Esham, Benjamin; Becker, William; Pogozelski, Edward; Padalino, Stephen; Sangster, Thomas; Glebov, Vladimir

2008-11-01

The High-Speed Rapid Pneumatic Transport of Radioactive Samples (HS-RaPToRS) system, designed to quickly and safely move radioactive materials, was assembled and tested at the Mercury facility of the Naval Research Laboratory (NRL) in Washington D.C. A sample, which is placed inside a four-inch-diameter carrier, is activated before being transported through a PVC tube via airflow. The carrier travels from the reaction chamber to the end station where it pneumatically brakes prior to the gate. A magnetic latch releases the gate when the carrier arrives and comes to rest. The airflow, optical carrier-monitoring devices, and end gate are controlled manually or automatically with LabView software. The installation and testing of the RaPToRS system at NRL was successfully completed with transport times of less than 3 seconds. The speed of the carrier averaged 16 m/s. Prospective facilities for similar systems include the Laboratory for Laser Energetics and the National Ignition Facility.

Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis.

PubMed

Tsujimura, Shizuyo; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya

2010-04-01

P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.

Salivary cortisol levels, but not salivary α-amylase levels, are elevated in patients with rheumatoid arthritis irrespective of depression.

PubMed

Kim, Hyoun-Ah; Jeon, Ja-Young; Koh, Bo-Ram; Park, Sat-Byul; Suh, Chang-Hee

2016-02-01

Stress is recognized as an important factor in the etiology of rheumatoid arthritis (RA). Therefore, we explored multiple aspects of stress in RA patients. Salivary cortisol and α-amylase levels were measured as markers of the hypothalamic-pituitary-adrenal axis activity and sympatho-adrenomedullary system activity, respectively. Depression was assessed by the Beck Depression Inventory (BDI) and short-term analysis of the heart rate variability (HRV) was performed to evaluate the autonomic nervous system. The salivary cortisol levels of the RA patients were significantly higher than those of the normal controls (NC; 0.12 ± 0.162 μg/dL vs. 0.068 ± 0.052 μg/dL, P = 0.006). There was no difference in salivary α-amylase levels between the RA and the NC. The BDI levels of the RA patients were significantly higher than the NC (13.7 ± 8.9 vs. 6.4 ± 6.9, P < 0.001). Depression was more prevalent in RA patients than in the NC. The salivary cortisol levels were still significantly higher in the RA than the NC after controlling BDI by logistic regression analysis (P = 0.002). There was no significant difference in the HRV of RA patients and the NC. The evaluation of relationship between stress measures and disease activity markers of RA revealed that only BDI was positively correlated with the visual analogue pain scale. Salivary cortisol levels and the BDI of RA patients were higher than those of the NC, and elevated salivary cortisol levels were independent of depression. However, the level of stress may not be correlated with disease activity in RA. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Self-assessment of Rheumatoid Arthritis Disease Activity Using a Smartphone Application. Development and 3-month Feasibility Study.

PubMed

Nishiguchi, S; Ito, H; Yamada, M; Yoshitomi, H; Furu, M; Ito, T; Shinohara, A; Ura, T; Okamoto, K; Aoyama, T; Tsuboyama, Tadao

2016-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". Rheumatoid arthritis (RA) is a progressive inflammatory disease that causes damage to multiple joints, decline in functional status, and premature mortality. Thus, effective and frequent objective assessments are necessary. Then, we developed a self-assessment system for RA patients based on a smartphone application. The purpose of this study was to investigate the feasibility of a self-assessment system for RA patients using a smartphone application. We measured daily disease activity in nine RA patients who used the smartphone application for a period of three months. A disease activity score (DAS28) predictive model was used and feedback comments relating to disease activity were shown to patients via the smartphone application each day. To assess participants' RA disease activity, the DAS28 based on the C-reactive protein level was measured by a rheumatologist during monthly clinical visits. The disease activity measured by the application correlated well with the patients' actual disease activity during the 3-month period, as assessed by clinical examination. Furthermore, most participants gave favourable responses to a questionnaire administered at the end of the 3-month period containing questions relating to the ease of use and usefulness of the system. The results of this feasibility study indicated that the DAS28 predictive model can longitudinally predict DAS28 and may be an acceptable and useful tool for assessment of RA disease activity for both patients and healthcare providers.

IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells.

PubMed

Elshabrawy, Hatem A; Volin, Michael V; Essani, Abdul B; Chen, Zhenlong; McInnes, Iain B; Van Raemdonck, Katrien; Palasiewicz, Karol; Arami, Shiva; Gonzalez, Mark; Ashour, Hossam M; Kim, Seung-Jae; Zhou, Guofei; Fox, David A; Shahrara, Shiva

2018-05-01

IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

Chronic comorbidity in patients with early rheumatoid arthritis: a descriptive study.

PubMed

Kroot, E J; van Gestel, A M; Swinkels, H L; Albers, M M; van de Putte, L B; van Riel, P L

2001-07-01

To study the presence of chronic coexisting diseases in patients with rheumatoid arthritis (RA) and its effect on RA treatment, disease course, and outcome during the first years of the disease. From January 1985 to December 1990, 186 patients with recent onset RA were enrolled in a prospective longitudinal study. Between January 1991 and November 1992 patients were interviewed on the basis of a comorbidity questionnaire. For analysis the diseases were coded according to the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) medical diagnoses. Disease activity during the period of followup was measured by the Disease Activity Score. Outcome in terms of physical disability (Health Assessment Questionnaire) and radiological damage (Sharp's modified version) over 3 and 6 year periods was determined. In the group of 186 patients, with mean disease duration of 4.3 years at January 1991, 50 patients (27%) reported at least one chronic coexisting disease. The most frequently reported coexisting diseases were of cardiovascular (29%), respiratory (18%), or dermatological (11%) origin. For the major part (66%) chronic coexisting diseases were already present before onset of RA. No statistically significant differences in use of disease modifying antirheumatic drugs or corticosteroids were observed between RA patients with and without chronic coexisting diseases. No statistically significant differences were found in disease activity or in outcome in terms of physical disability and radiological damage over 3 and 6 year periods between the 2 groups with RA. The results showed that about 27% of patients with RA in this inception cohort had at least one chronic coexisting disease. Treatment, disease course, and outcome did not differ between patients with and without chronic coexisting diseases during the first years of the disease.

Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): results from the CanACT study.

PubMed

Haraoui, Boulos; Cividino, Alfred; Stewart, Jacqueline; Guérette, Benoît; Keystone, Edward C

2011-11-17

This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA). Patients ≥ 18 years of age with a history of active RA ≥ 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naïve to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events. A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low-disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naïve to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were

Using Tidal Fluctuation-Induced Dynamics of Radium Isotopes (224Ra, 223Ra, and 228Ra) to Trace the Hydrodynamics and Geochemical Reactions in a Coastal Groundwater Mixing Zone

NASA Astrophysics Data System (ADS)

Liu, Yi; Jiao, Jiu Jimmy; Liang, Wenzhao; Luo, Xin

2018-04-01

The reactive transport of radium isotopes (224Ra, 223Ra, and 228Ra) in coastal groundwater mixing zones (CGMZs) is sensitive to shifts of redox conditions and geochemical reactions induced by tidal fluctuation. This study presents a spatial distribution and temporal variation of radium isotopes in the CGMZ for the first time. Results show that the activity of radium isotopes in the upper saline plume (USP) is comparatively low due to a short residence time and mixing loss induced by the infiltration of low radium seawater whereas the activity of radium isotopes in the salt wedge (SW) is comparatively high due to a long residence time in the aquifer. The spatial distribution of radium isotopes is determined by the partitioning of radium isotopes, groundwater residence time, and relative ingrowth rates of radium isotopes. In addition, the variation of radium isotopes in the USP lags slightly (˜0 h) whereas the fluctuation of radium isotopes in the SW lags significantly (˜12 h) behind sea level oscillation. Tidal fluctuation affects the partitioning of radium isotopes through controlling seawater infiltration and subsequently influences the dynamics of radium isotopes in the USP. Concurrently, seawater infiltration significantly affects geochemical processes such as the production of nutrients and total alkalinity. Therefore, radium dynamics in the USP have implications for these geochemical processes. The variation of radium isotopes in the USP also has potential implications for transformation of trace metals such as iron and manganese because of the close affinity of radium isotopes to manganese and iron oxides.

Patient Expectations and Perceptions of Goal-setting Strategies for Disease Management in Rheumatoid Arthritis.

PubMed

Strand, Vibeke; Wright, Grace C; Bergman, Martin J; Tambiah, Jeyanesh; Taylor, Peter C

2015-11-01

To identify how patients perceive the broad effect of active rheumatoid arthritis (RA) on their daily lives and indicate how RA disease management could benefit from the inclusion of individual goal-setting strategies. Two multinational surveys were completed by patients with RA. The "Good Days Fast" survey was conducted to explore the effect of disease on the daily lives and relationships of women with RA. The "Getting to Your Destination Faster" survey examined RA patients' treatment expectations and goal-setting practices. Respondents from all countries agreed that RA had a substantial negative effect on many aspects of their lives (work productivity, daily routines, participation in social and leisure activities) and emotional well-being (loss of self-confidence, feelings of detachment, isolation). Daily pain was a paramount issue, and being pain- and fatigue-free was considered the main indicator of a "good day." Setting personal, social, and treatment goals, as well as monitoring disease progress to achieve these, was considered very beneficial by patients with RA, but discussion of treatment goals seldom appeared to be a part of medical appointments. Many patients with RA feel unable to communicate their disease burden and treatment goals, which are critically important to them, to their healthcare provider (HCP). Insights gained from these 2 surveys should help to guide patients and HCP to better focus upon mutually defined goals for continued improvement of management and achievement of optimal care in RA.

Disease activity, obesity, functional disability, and depression in patients with rheumatoid arthritis : Impact on lipid status, glycoregulation, and risk for coronary heart disease.

PubMed

Ostojic, P; Bartolovic, D

2016-09-01

This study aims to estimate the impact of disease activity, obesity, functional disability, and depression on lipid status, glycoregulation, and risk for coronary heart disease (CHD) in patients with rheumatoid arthritis (RA). A total of 36 patients with RA (30 women and 6 men, mean age 54.9 years, mean disease duration 7.9 years) were included in this study. We estimated the impact of age, body mass index, disease activity [assessed by DAS28 index and C-reactive protein (CRP) value], functional ability (estimated using the HAQ disability index), and depression [assessed using the Beck Depression Inventory (BDI)] on glycoregulation, lipid status, and risk for CHD in our patients. Glycoregulation was assessed by measuring insulin resistance, insulin, and glucose in blood. Lipids tested in blood included total cholesterol, HDL and LDL cholesterol, and triglycerides (TG). The 10-year risk for CHD was estimated using the Framingham risk score. Of 36 patients, 11 (30.6 %) fulfilled the criteria for metabolic syndrome (MS). Ten of 11 patients (90.1 %) with MS have a 10-year risk for CHD greater than 10 % compared to only 3 of 25 patients (12 %) without MS (p = 0.0001). Patients with high disease activity had lower HDL values than patients with mild or moderate disease activity (1.4 vs. 1.7 mmol/l, p = 0.04). Significant correlations were observed between CRP level and insulinemia (ρ = 0.57, p = 0.003), as well as CRP level and the HOMA index (ρ = 0.59, p = 0.002). The body mass index (BMI) correlated significantly with total cholesterol (r = 0.46, p = 0.02), LDL (ρ = 0.41, p = 0.04), and TG (ρ = 0.65, p < 0.001) in blood. The HAQ-DI did not correlate either with parameters of glycoregulation or lipid status. There was a significant positive correlation between BDI and BMI (ρ = 0.60, p < 0.001). Active RA is independently associated with decreased HDL cholesterol and increased insulin resistance

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

PubMed

AbouAssi, Hiba; Connelly, Margery A; Bateman, Lori A; Tune, K Noelle; Huebner, Janet L; Kraus, Virginia B; Winegar, Deborah A; Otvos, James D; Kraus, William E; Huffman, Kim M

2017-02-10

In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile. NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008-13, this study was not registered in

Evaluation of Learned Helplessness, Perceived Self-efficacy, and Functional Capacity in Patients With Fibromyalgia and Rheumatoid Arthritis.

PubMed

Moyano, Sebastián; Scolnik, Marina; Vergara, Facundo; García, María Victoria; Sabelli, Mirtha Rosa; Rosa, Javier Eduardo; Catoggio, Luis José; Soriano, Enrique Roberto

2018-03-19

The aims of this study were to compare learned helplessness (LH) and perceived self-efficacy (SE) in patients with fibromyalgia (FM) and rheumatoid arthritis (RA) and to assess their correlation with functional disability, level of perceived pain, and fatigue. This multicenter, cross-sectional study included consecutive patients (aged ≥18 years) with RA, according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and FM, according to 2010 American College of Rheumatology criteria. Learned helplessness was measured by the Rheumatology Attitude Index, Spanish version; SE with the Arthritis Self-efficacy Scale, Spanish version; functional capacity with the Health Assessment Questionnaire (HAQ), Argentine version; depression with Center for Epidemiological Studies-Depression Scale 7-item version and perceived pain and fatigue by the visual analog scale. Disease activity was measured by the Clinical Disease Activity Index (CDAI) and disease impact with the Fibromyalgia Impact Questionnaire (FIQ). A total of 215 patients, 100 with FM and 115 with RA, were included. Mean age was 59 (SD, 14) years and 58 (SD, 13) years for FM and RA, patients respectively. Whereas LH and depression were significantly higher, SE was significantly lower in FM patients. We found a positive correlation between LH and HAQ, pain, depression, fatigue, FIQ, and CDAI in FM and RA patients. We observed a negative correlation between SE and HAQ, pain, depression, fatigue, FIQ (FM), and CDAI (RA) in both groups. Both LH and SE correlate significantly with functional capacity, perceived pain, disease activity, and disease impact in RA and FM patients. Learned helplessness was higher in patients with active disease or high disease impact, as opposed to those in remission or with low disease impact, and the reverse was true for SE. Patients with FM had significantly more LH, pain, fatigue, and depression and less SE compared with those with RA.

The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort study.

PubMed

Kirkeskov, Bente; Christensen, Robin; Bügel, Susanne; Bliddal, Henning; Danneskiold-Samsøe, Bente; Christensen, Lars Porskjær; Andersen, Jens Rikardt

2011-08-15

Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxidant nutrients and an anti-inflammatory galactolipid. Rheumatoid arthritis (RA) is an inflammatory disease where activated cells release reactive oxygen substances. Thus it could be relevant to investigate if rose hip had an anti-inflammatory and/or antioxidant effect in this situation. In this open case-control study 20 female patients with RA and 10 female controls were given 10.5 g rose hip powder daily (Litozin®) for 28 days. Blood samples were analysed at baseline and follow-up for the capacity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase and the inflammatory marker C-reactive protein (CRP). The participants kept a food diary for the first 3 days and the last 3 days of the intervention period. The RA-patients completed The Stanford Health Assessment Questionnaire at baseline and follow-up. CRP-concentrations of both patients and healthy controls did not change. Nor was any effect found on the activity of antioxidant enzymes. There was no difference in food intake at baseline, but in the last week the RA-group reduced their energy intake. 10.5 g Litozin® in 28 days had neither effect on clinical symptoms or laboratory measurements in patients with RA or healthy controls. This is in contrast to previous intervention studies with rose hip powder that found a reduction in the concentration of CRP. The results of the present study indicate that a daily amount of approximately 10 g rose hip powder for one month has no anti-inflammatory and/or antioxidant effect. Copyright © 2011 Elsevier GmbH. All rights reserved.

Rapid determination of 226Ra in environmental samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxwell, Sherrod L.; Culligan, Brian K.

A new rapid method for the determination of {sup 228}Ra in natural water samples has been developed at the SRNL/EBL (Savannah River National Lab/ Environmental Bioassay Laboratory) that can be used for emergency response or routine samples. While gamma spectrometry can be employed with sufficient detection limits to determine {sup 228}Ra in solid samples (via {sup 228}Ac) , radiochemical methods that employ gas flow proportional counting techniques typically provide lower MDA (Minimal Detectable Activity) levels for the determination of {sup 228}Ra in water samples. Most radiochemical methods for {sup 228}Ra collect and purify {sup 228}Ra and allow for {sup 228}Acmore » daughter ingrowth for ~36 hours. In this new SRNL/EBL approach, {sup 228}Ac is collected and purified from the water sample without waiting to eliminate this delay. The sample preparation requires only about 4 hours so that {sup 228}Ra assay results on water samples can be achieved in < 6 hours. The method uses a rapid calcium carbonate precipitation enhanced with a small amount of phosphate added to enhance chemical yields (typically >90%), followed by rapid cation exchange removal of calcium. Lead, bismuth, uranium, thorium and protactinium isotopes are also removed by the cation exchange separation. {sup 228}Ac is eluted from the cation resin directly onto a DGA Resin cartridge attached to the bottom of the cation column to purify {sup 228}Ac. DGA Resin also removes lead and bismuth isotopes, along with Sr isotopes and {sup 90}Y. La is used to determine {sup 228}Ac chemical yield via ICP-MS, but {sup 133}Ba can also be used instead if ICP-MS assay is not available. Unlike some older methods, no lead or strontium holdback carriers or continual readjustment of sample pH is required.« less

Grb7 protein RA domain oligomerization.

PubMed

Godamudunage, Malika P; Foster, Albert; Warren, Darius; Lyons, Barbara A

2017-08-01

The growth factor receptor bound protein 7 (Grb7) is an adaptor protein that is often coamplified with the erythroblastosis oncogene B 2 receptor in 20% to 30% of breast cancer patients. Grb7 overexpression has been linked to increased cell migration and cancer metastasis. The ras associating and pleckstrin homology domain region of Grb7 has been reported to interact with various other downstream signaling proteins such as four and half Lin11, Isl-1, Mec-3 (LIM) domains isoform 2 and filamin α. These interactions are believed to play a role in regulating Grb7-mediated cell migration function. The full-length Grb7 protein has been shown to dimerize, and the oligomeric state of the Grb7SH2 domain has been extensively studied; however, the oligomerization state of the ras associating and pleckstrin homology domains, and the importance of this oligomerization in Grb7 function, is yet to be fully known. In this study, we characterize the oligomeric state of the Grb7RA domain using size exclusion chromatography, nuclear magnetic resonance, nuclear relaxation studies, glutaraldehyde cross linking, and dynamic light scattering. We report the Grb7RA domain can exist in transient multimeric forms and, based upon modeling results, postulate the potential role of Grb7RA domain oligomerization in Grb7 function. Copyright © 2017 John Wiley & Sons, Ltd.

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

PubMed Central

Arleevskaya, Marina I.; Shafigullina, Albina Z.; Filina, Yulia V.; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further. PMID:29259607

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

PubMed

Arleevskaya, Marina I; Shafigullina, Albina Z; Filina, Yulia V; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

Assessment of rheumatoid arthritis patients' adherence to treatment.

PubMed

Gadallah, Mohsen A; Boulos, Dina N K; Gebrel, Asmaa; Dewedar, Sahar; Morisky, Donald E

2015-02-01

Reports on adherence among patients with rheumatoid arthritis (RA) in Egypt and the Middle East region are lacking. This study aimed to measure adherence to treatment among a sample of patients with RA at Ain Shams University Rheumatology outpatient clinic and to assess factors affecting it. A cross-sectional descriptive study was carried out at the rheumatology outpatient clinic on a sample of 140 patients with RA. An interview questionnaire was used to measure adherence using the 8-item Morisky's scale, factors affecting adherence to treatment like patients satisfaction were assessed using the short form patient satisfaction questionnaire, also patients' knowledge, beliefs and rate of prescription refilling were assessed. Disease Activity Score-28 was used as an objective method to assess RA disease activity. According to Morisky's scale, 90.6% and 9.4% were classified as low and moderately adherent, respectively, none was classified as highly adherent to treatment. Important barriers to adherence reported were fear of side effects, nonavailability of free drugs in hospital pharmacy and cost of medications. Younger patients (P=0.002) and those reporting greater general satisfaction (P=0.02) were more likely to be adherent. In addition, on-time refill rates of medication (P=0.001) and disease activity (P=0.02) were associated with higher adherence scores and thus further validated the results of the adherence questionnaire. Higher adherence was associated with more positive beliefs on medication, greater satisfaction with health care and less disease activity.

Assessment of Corneal and Tear Film Parameters in Rheumatoid Arthritis Patients Using Anterior Segment Spectral Domain Optical Coherence Tomography.

PubMed

El-Fayoumi, Dina; Youssef, Maha Mohamed; Khafagy, Mohamed Mahmoud; Badr El Dine, Nashwa; Gaber, Wafaa

2018-01-01

To study the corneal changes in rheumatoid arthritis (RA) patients in vivo, using spectral domain anterior segment optical coherence tomography (AS-OCT). A case-control study was done on 43 RA patients and 40 controls. The disease activity score (DAS28-ESR) was calculated and all participants had lower tear meniscus, corneal thickness, and epithelial thickness evaluation using AS-OCT. The lower tear meniscus height (LTMH) and the lower tear meniscus area (LTMA) were significantly lower in the RA patients than in controls (p < 0.001). RA patients also had a significantly thinner central corneal thickness (p = 0.02) and their epithelium was found to be thinner in the superotemporal peripheral sector. The LTMH and LTMA are significantly reduced in RA patients, despite the absence of clinical diagnosis of dry eye. RA patients have thinner corneal thickness and epithelial thickness than controls, which did not correlate with either disease duration or activity.

68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer.

PubMed

Ahmadzadehfar, Hojjat; Schlenkhoff, Carl Diedrich; Rogenhofer, Sebastian; Yordanova, Anna; Essler, Markus

2016-09-01

A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases.

Tretinoin cyclodextrin complex (RA/CyD) causes less irritation with an equal antiwrinkle effect compared with conventional tretinoin: clinical and histologic studies of photoaged skin.

PubMed

Miura, Tomoe; Takada, Akiyoshi; Ooe, Masahiko

2012-08-01

Topical tretinoin [all-trans-retinoic acid (RA)] currently is widely used to treat photoaged skin. However, undesirable side effects such as erythema, irritation, and scaling are unavoidable and limit the use of tretinoin. To address these issues, the authors developed the tretinoin cyclodextrin complex (RA/CyD), which is tretinoin encapsulated by cyclodextrin. Cyclodextrins are cyclic oligosaccharides commonly used in food additives and fabric fresheners. This study aimed to evaluate the antiwrinkle effect of RA/CyD and alleviation of the side effects compared with RA treatment alone. In this study, 12 photoaged patients completed an 8 week study using RA and RA/CyD in a double-blind manner. Before and after the treatment, the patients' evaluations, wrinkle scores, skin elasticity, and wrinkle area measurement using skin replica were evaluated. Three men were recruited for histologic analysis. The patients reported that undesirable irritant reactions were more moderate with RA/CyD than with RA. In the assessment of wrinkle scores, skin elasticity, and wrinkle area measurement, RA/CyD demonstrated an antiwrinkle effect statistically equal to that of RA. In histology, both RA/CyD and RA demonstrated epidermal hyperplasia. In immunohistochemistry, inflammation induced by RA/CyD was more moderate than that induced by RA. The findings show that RA and RA/CyD result in the equivalent clinical improvement for patients with photoaging. The use of RA/CyD overcomes the drawbacks of RA while possessing equal effect. It is expected that CyD will broaden tretinoin treatment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

PubMed

Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

2016-03-01

To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

The practice of physical activity and cryotherapy in rheumatoid arthritis: systematic review.

PubMed

Peres, Daniele; Sagawa, Yoshimasa; Dugué, Benoit; Domenech, Susana C; Tordi, Nicolas; Prati, Clement

2017-10-01

Rheumatoid arthritis (RA) is an autoimmune, chronic and inflammatory disease, which the affected patients present a higher cardiovascular mortality rate. Physical activities have been identified as the most important strategy to prevent cardiovascular diseases. However, the articular damage and the chronic pain caused by RA challenges its regular practice. Moreover, persons with RA tend to avoid PA due to the fear of exacerbating the inflammatory potential and pain. One alternative to avoid the collateral effects of the PA could be the cryotherapy. Therefore, this study aimed to review studies focused on the use of both PA and cryotherapy in RA patients and to identify evidences that both therapies could be combined in order to optimize the symptomatic treatment. Four databases (MEDLINE, CINAHL, Elsevier and PEDro) were searched to identify publications regarding RA patients, PA and cryotherapy intervention by the terms and operators (rheumatoid arthritis AND exercise OR physical activity OR activity OR training OR reconditioning OR cryotherapy OR cold OR immersion). The selected studies should at least present one measure of the aerobic capacity, disease activity or pain relief. Among 19 studies with RA patients identified, only 4 studies used PA combined with cryotherapy. The other 13 studies used physical activities and 2 studies used cryotherapy intervention. The results of the physical activities combined with cryotherapy studies showed an improvement in the disease activity and pain relief, however without details of the physical activities intervention and an aerobic capacity. Among the physical activities studies, evidence was found suggesting that aerobic exercises and multiactivity exercises with high intensity are the more effective for improve the aerobic capacity. Even if few studies on cryotherapy were found, there are enough evidences in the literature that demonstrate the benefits of this intervention on pain relief and disease activity. In summary

VELoCiRaPTORS.

NASA Astrophysics Data System (ADS)

Lundgren, J.; Esham, B.; Padalino, S. J.; Sangster, T. C.; Glebov, V.

2007-11-01

The Venting and Exhausting of Low Level Air Contaminants in the Rapid Pneumatic Transport of Radioactive Samples (VELoCiRaPTORS) system is constructed to transport radioactive materials quickly and safely at the NIF. A radioactive sample will be placed inside a carrier that is transported via an airflow system produced by controlled differential pressure. Midway through the transportation process, the carrier will be stopped and vented by a powered exhaust blower which will remove radioactive gases within the transport carrier. A Geiger counter will monitor the activity of the exhaust gas to ensure that it is below acceptable levels. If the radiation level is sufficient, the carrier will pass through the remainder of the system, pneumatically braking at the counting station. The complete design will run manually or automatically with control software. Tests were performed using an inactive carrier to determine possible transportation problems. The system underwent many consecutive trials without failure. VELoCiRaPTORS is a prototype of a system that could be installed at both the Laboratory for Laser Energetics at the University of Rochester and the National Ignition Facility at LLNL.

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study.

PubMed

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Yamamoto, Kazuhiko; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2018-04-27

We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA). This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52. Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52. Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

Validity and Agreement between the 28-Joint Disease Activity Score Based on C-Reactive Protein and Erythrocyte Sedimentation Rate in Patients with Rheumatoid Arthritis

PubMed Central

Nielung, Louise; Christensen, Robin; Danneskiold-Samsøe, Bente; Bliddal, Henning; Holm, Christian Cato; Ellegaard, Karen; Slott Jensen, Hanne; Bartels, Else Marie

2015-01-01

Objective. To validate the agreement between the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in a group of Danish patients with rheumatoid arthritis (RA). Methods. Data from 109 Danish RA patients initiating biologic treatment were analysed at baseline and following one year of treatment. Participants were retrospectively enrolled from a previous cohort study and were considered eligible for this project if CRP and ESR were measured at baseline and at the follow-up visit. To assess the extent of agreement between the two DAS28 definitions, the “European League Against Rheumatism” (EULAR) response criteria based on each definition were calculated with cross-classification. Weighted Kappa (κ) coefficients were calculated, and Bland-Altman plots were used to illustrate degree of agreement between DAS28 definitions. Results. The 75 eligible patients were classified as EULAR good, moderate, and nonresponders with good agreement (61/75; 81%) between DAS28-CRP and DAS28-ESR (κ = 0.75 (95% CI: 0.63 to 0.88)). Conclusions. According to our findings, DAS28-CRP and DAS28-ESR are interchangeable when assessing RA patients and the two versions of DAS28 are comparable between studies. PMID:25632353

Relevance of P-glycoprotein on CXCR4+ B cells to organ manifestation in highly active rheumatoid arthritis.

PubMed

Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Kawabe, Akio; Tanaka, Yoshiya

2018-03-01

In rheumatoid arthritis (RA), P-glycoprotein (P-gp) expression on activated B cells is associated with active efflux of intracellular drugs, resulting in drug resistance. CXCR4 is associated with migration of B cells. This study was designed to elucidate the relevance of P-gp expression on CXCR4 + B cells to clinical manifestations in refractory RA. CD19 + B cells were analyzed using flow cytometry and immunohistochemistry. P-gp was highly expressed especially on CXCR4 + CD19 + B cells in RA. The proportion of P-gp-expressing CXCR4 + B cells correlated with disease activity, estimated by Simplified Disease Activity Index (SDAI), and showed marked expansion in RA patients with high SDAI and extra-articular involvement. In highly active RA, massive infiltration of P-gp + CXCR4 + CD19 + B cells was noted in CXCL12-expressing inflammatory lesions of RA synovitis and RA-associated interstitial pneumonitis. In RA patient with active extra-articular involvement, intracellular dexamethasone level (IDL) in lymphocytes diminished with expansion of P-gp + CXCR4 + CD19 + B cells. Adalimumab reduced P-gp + CXCR4 + CD19 + B cells, increased IDL in lymphocytes, and improved the clinical manifestation and allowed tapering of concomitant medications. Expansion of P-gp + CXCR4 + B cells seems to be associated with drug resistance, disease activity and progressive destructive arthritis with extra-articular involvement in RA.

Correlation between bone quality and microvascular damage in systemic sclerosis patients.

PubMed

Ruaro, Barbara; Casabella, Andrea; Paolino, Sabrina; Pizzorni, Carmen; Alessandri, Elisa; Seriolo, Chiara; Botticella, Giulia; Molfetta, Luigi; Odetti, Patrizio; Smith, Vanessa; Cutolo, Maurizio

2018-05-18

SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, by trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Eighty-four SSc patients, 98 RA patients and 60 CNT, were studied. BMD (g/cm2) of the lumbar spine (L1-L4) was analysed by DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed. A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA and BMD was found to be significantly lower than in the CNT (P < 0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (P < 0.001). TBS values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs active and early pattern, P < 0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (P = 0.238). The data obtained showed significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern).

Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

PubMed

Pérez-Dórame, Renzo; Mejía, Mayra; Mateos-Toledo, Heidegger; Rojas-Serrano, Jorge

2015-01-01

To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: correlation with disease activity and bone destruction.

PubMed

Xu, L; Hu, F; Zhu, H; Liu, X; Shi, L; Li, Y; Zhong, H; Su, Y

2018-04-01

The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in patients with RA. A total of 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled into this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by enzyme-linked immunosorbent assay (ELISA), then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analysed. We also investigated whether sTyro3 could promote osteoclast differentiation in vitro in RA patients. The results showed that compared with healthy controls (HCs), sTyro3 levels in the serum of RA patients were elevated remarkably and sMer levels were decreased significantly, whereas there was no difference between HCs and RA patients on sAxl levels. The sTyro3 levels were correlated weakly but positively with white blood cells (WBC), immunoglobulin (Ig)M, rheumatoid factor (RF), swollen joint counts, tender joint counts, total sharp scores and joint erosion scores. Conversely, there were no significant correlations between sMer levels and the above indices. Moreover, RA patients with high disease activity also showed higher sTyro3 levels. In-vitro osteoclast differentiation assay showed further that tartrate-resistant acid phosphatase (TRAP) + osteoclasts were increased significantly in the presence of sTyro3. Collectively, our study indicated that serum sTyro3 levels were elevated in RA patients and correlated positively with disease activity and bone destruction, which may serve as an important participant in RA pathogenesis. © 2017 British Society for Immunology.

Inhibition of Endothelial Progenitor Cells May Explain the High Cardiovascular Event Rate in Patients with Rheumatoid Arthritis.

PubMed

Adawi, Mohamad; Pastuck, Nina; Saaida, Golan; Sirchan, Rizak; Watad, Abdalla; Blum, Arnon

2018-05-16

Rheumatoid arthritis (RA) patients may suffer cardiovascular (CV) events much more than the general population, and CV disease is the leading cause of death in patients with RA. Our hypothesis was that impaired function of endothelial progenitor cells may contribute to endothelial dysfunction and the clinical CV events of patients with RA. 27 RA patients (9 males and 18 females) with an active disease and 13 healthy subjects who served as the control group (9 males and 4 females) were enrolled to this prospective study. The ability to grow in culture colony-forming units of endothelial progenitor cells (CFU-EPCs) was measured, as well as their endothelial function using high-resolution ultrasonography of the brachial artery, and levels of C reactive protein (CRP) in the serum. For statistical analysis we used the students T-test test. As a group, patients with RA were older (p < 0.0001), had severe endothelial dysfunction (<0.0001), with impaired ability to grow CFU-EPCs (<0.0001), and a higher inflammatory state (p = 0001). No difference was observed in BMI. All RA patients had an active disease (DAS28 3.9±0.9) for 9.2±6.5 years. The same differences were observed in both genders. Patients with RA had an impaired ability to grow endothelial progenitor cells and severe endothelial dysfunction. Inability to grow colonies of endothelial progenitor cells reflects the impaired regenerative capacity of patients with RA, and may explain the endothelial dysfunction and the high CV event rate among patients with RA.

Tocilizumab treatment leads to improvement in disease activity regardless of CCP status in rheumatoid arthritis.

PubMed

Cappelli, Laura C; Palmer, Judy Lynn; Kremer, Joel; Bingham, Clifton O

2017-10-01

Autoantibodies can be useful in predicting response to certain treatments in rheumatoid arthritis (RA). We aimed to evaluate initial response to tocilizumab (TCZ) by change in physician and patient-reported outcomes and laboratory parameters in a real-world cohort of patients with RA. We analyzed the data by autoantibody status to determine whether patients with seronegative RA had improved response to tocilizumab when compared to their seropositive counterparts. Data from the CORRONA RA registry were analyzed. Patients were included if they were started on TCZ and had data from a follow-up visit 4-8 months after initiation, as well as having information on serologic status. Serologic status was determined by presence of anti-cyclic citrullinated peptide (CCP) antibodies. Changes in disease activity measures from baseline to follow-up visit were evaluated. Both CCP-negative and -positive groups had statistically significant improvement in physician-reported measurements (physician rating of disease activity and joint counts), patient-reported measures (disease activity, pain, and fatigue), and acute phase reactants after 4-8 months of treatment with tocilizumab. The magnitude of improvement, however, did not differ significantly by CCP status. Tocilizumab led to statistically significant improvement in all patient- and physician-reported measures of disease activity evaluated in this cohort of patient with RA. The response to tocilizumab did not differ by CCP status. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence and factors associated with metabolic syndrome in patients with rheumatoid arthritis and systemic lupus erythematosus.

PubMed

Zonana-Nacach, Abraham; Santana-Sahagún, Ernesto; Jiménez-Balderas, Francisco Javier; Camargo-Coronel, Adolfo

2008-04-01

To assess the frequency and factors associated with metabolic syndrome in adult female patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). During January and June 2006, 192 consecutive adult female patients seen during their scheduled appointment at the out-patient rheumatology clinic and meeting the American College of Rheumatology classification criteria for RA and SLE were invited to participate in this study. Sociodemographic, menopausal status, personal history of coronary heart disease, and physical activity were evaluated. According to the National Cholesterol Education Program Adult Treatment III (NCEP/ATP III), metabolic syndrome was defined as >or=3 of the following criteria: increased waist circumference (>88 cm or 35 inches), hypertriglyceridemia (>or=150 mg/dL), low (<40 mg/dL) high-density lipoprotein, hypertension, and high fasting glucose (>or=110 mg/dL). : One hundred-seven RA and 85 SLE patients with a mean age of 43 +/- 13 years were included in this study. The frequency of obesity and abnormal waist circumference were similar in RA and SLE patients. Two percent were underweight, 35% had a normal weight, 37% were overweight, and 25% were obese. The frequency of metabolic syndrome in RA and SLE patients was 17%. Metabolic syndrome was significantly associated with greater age, less education, lower income, and smoking. In RA patients, metabolic syndrome was significantly associated with a shorter treatment period with methotrexate, with pain, and with health assessment questionnaire scores. By multivariate logistic regression, the only statistically significant predictor of metabolic syndrome was smoking. The frequency of metabolic syndrome in RA and SLE patients was similar and associated with smoking. In RA patients, metabolic syndrome was related with pain and functional status, suggesting disease activity. A better control of disease activity may reduce the presence of metabolic syndrome and the risk of

Migration area of the Tsushima Warm Current Branches within the Sea of Japan: Implications from transport of 228Ra

NASA Astrophysics Data System (ADS)

Inoue, M.; Shirotani, Y.; Furusawa, Y.; Fujimoto, K.; Kofuji, H.; Yoshida, K.; Nagao, S.; Yamamoto, M.; Hamajima, Y.; Honda, N.; Morimoto, A.; Takikawa, T.; Shiomoto, A.; Isoda, Y.; Minakawa, M.

2017-07-01

We investigated lateral profiles of 228Ra (half-life; 5.75 years) activity and 228Ra/226Ra (1600 years) activity ratio using 241 surface water samples collected in/around the Sea of Japan and the East China Sea (ECS) during June-October of 2009-2014. In the ECS, the 228Ra/226Ra ratio in the surface waters exhibited markedly wide variation (<0.05-3.5) in June, predominantly reflecting the mixing between the 228Ra-rich continental shelf water and the 228Ra-depleted Kuroshio Current water. In July, the surface waters of the central Sea of Japan (135-138°E) became separated into three currents: the Offshore Branch of the Tsushima Warm Current (OBTWC) (228Ra/226Ra =0.7-1.2) at 39-41°N, the Coastal Branch of the TWC (CBTWC) ( 0.7) on the southern side, and sub-Arctic Current ( 0.7) on the northern side. From the central to northeastern Sea of Japan, the 228Ra/226Ra ratio at the surface (0.8-1.0) was within a range between that of the CBTWC and OBTWC. The fraction of continental shelf water in the CBTWC, OBTWC, and in their combined current was estimated to be 11-16%, 8%, and 10-11%, respectively.

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

PubMed Central

Nema, Hiroaki; Kato, Mototsugu

2010-01-01

AIM: To compare the therapeutic effects of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin. METHODS: Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine 40 mg or if famotidine had been administered before assignment, ranitidine 300 mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk treatment. The presence or absence of Helicobacter pylori (H. pylori) was determined by urea breath test before treatment. Abdominal symptoms were compared with the gastrointestinal symptom rating scale (GSRS) questionnaire before and after treatment. RESULTS: Twenty-six patients in the PPI group and 26 patients in the H2RA group, excluding dropouts, were analyzed. There were no significant differences in median age, sex, underlying disease, smoking status, H. pylori infection, prevalence of ulcers before treatment, and lesion site between the two groups. The therapeutic effects were endoscopically evaluated as healed in 23 patients (88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal symptoms before treatment were uncommon in both groups; the GSRS scores were not significantly reduced after treatment as compared with before treatment. CONCLUSION: The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group, with no significant difference between the two groups. PMID:21072898

"Redefining RA": The RA Tool Kit

ERIC Educational Resources Information Center

Wyatt, Neal

2008-01-01

No one likes being two steps behind, and the fastest way to fall off the pace is by not keeping up with major titles and hot authors. Fortunately, there are numerous resources, both prepublication and postpublication, that can help. It is best when readers' advisory (RA) librarians know what is coming out months ahead of time--in order to think…

Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells.

PubMed Central

Robinson, E; Keystone, E C; Schall, T J; Gillett, N; Fish, E N

1995-01-01

Earlier studies from this laboratory provided evidence for restricted cytokine expression in the T cell population in RA tissues. Specifically, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) gene expression levels were low. The selective chemoattractant and activation effects of chemokines on leucocytes identify them as potentially ideal candidates in mediating selective inflammatory processes in RA. Accordingly, we undertook studies to examine constitutive chemokine gene expression in RA tissues. RANTES, monocyte chemotactic protein-1 (MCP-1) and MIP-1 beta gene expression was examined in both the T and non-T cell populations in RA peripheral blood (PB), synovial fluid (SF) and synovial tissues (ST). Our results identified elevated levels of both RANTES and MIP-1 beta gene expression in circulating RA PB and SF T cells. By contrast, MCP-1 expression was virtually absent in RA PB, yet elevated MCP-1 mRNA levels were detected primarily in the non-T cell populations of the SF and ST samples. Histological examination of affected rheumatoid joints revealed extensive RANTES and MIP-1 beta expression in sites of lymphocyte infiltration and cell proliferation, namely the synovial lining and sublining layers. Fractionation or RA ST patient samples revealed that RANTES expression was restricted to the T cells, whereas MIP-1 beta expression was detected in both T and non-T fractions. These data suggest that MCP-1, MIP-1 beta and RANTES may have a central role in the trafficking of reactive molecules involved in immunoregulation and in the inflammatory processes in RA. Images Fig. 4 PMID:7545093

Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

PubMed Central

Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

2015-01-01

Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials using a multi-biomarker disease activity score as an inclusion criterion.

PubMed

van Vollenhoven, Ronald F; Bolce, Rebecca; Hambardzumyan, Karen; Saevarsdottir, Saedis; Forslind, Kristina; Petersson, Ingemar F; Sasso, Eric H; Hwang, C C; Segurado, Oscar G; Geborek, Pierre

2015-11-01

Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44." © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Relationship between leptin concentrations and disease activity in patients with rheumatoid arthritis.

PubMed

Batún-Garrido, José Antonio de Jesús; Salas-Magaña, Marisol; Juárez-Rojop, Isela Esther; Hernández-Núñez, Eúfrates; Olán, Francisco

2018-05-11

Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). The data suggest that serum leptin is elevated in patients with active RA. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Association between helplessness, disability, and disease activity with health-related quality of life among rheumatoid arthritis patients in a multiethnic Asian population.

PubMed

Kwan, Yu Heng; Koh, Ee Tzun; Leong, Khai Pang; Wee, Hwee-Lin

2014-08-01

To investigate the association between helplessness, disability, and disease activity with health-related quality of life (HRQoL) in a multiethnic cohort of rheumatoid arthritis (RA) patients in Singapore. This cross-sectional study was conducted at Tan Tock Seng Hospital, Department of Rheumatology, Allergy and Immunology, from October 2010 to October 2011. All patients fulfilled the American College of Rheumatology 1987 criteria for RA. Socio-demographics, clinical, and patient-reported outcome (PRO) variables were collected. HRQoL outcomes were Short Form 36 (SF-36) physical and mental component summary (PCS and MCS) scores and Short Form 6 Dimensions (SF-6D) utilities. Stepwise multiple linear regression analyses were performed using HRQoL outcomes as dependent variables in separate models and with adjustment for helplessness (Rheumatology Attitudes Index, RAI), disability (Health Assessment Questionnaire, HAQ), and disease activity (Disease Activity in 28 joints) followed by socio-demographic, clinical, and PRO variables. Complete data were provided by 473 consenting subjects [mean (SD) age: 60.02 (11.04) years, 85 % female, 77 % Chinese]. After adjustment for all measured covariates, only RAI and HAQ scores remained significantly associated with SF-36 MCS (β: -0.9, p < 0.001; β: -7.0, p < 0.001) and SF-6D utilities (β: -0.005, p < 0.001; β: -0.081, p < 0.001), respectively, while only HAQ scores were significantly associated with SF-36 PCS (β: -7.7, p < 0.001). Interventions to address the sense of helplessness and to prevent or reduce disability could improve HRQoL of RA patients.

Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity.

PubMed

Smolen, Josef S; Strand, Vibeke; Koenig, Andrew S; Szumski, Annette; Kotak, Sameer; Jones, Thomas V

2016-05-21

Discordance between patient and physician ratings of rheumatoid arthritis (RA) severity occurs in clinical practice and correlates with pain scores and measurements of joint disease. However, information is lacking on whether discordance impacts patients' ability to work. We evaluated the discordance between patient and physician ratings of RA disease activity before and after treatment with etanercept and investigated the associations between discordance, clinical outcomes, and work productivity. In the PRESERVE clinical trial, patients with moderate RA received open-label etanercept 50 mg once weekly plus methotrexate for 36 weeks. Baseline and week-36 disease characteristics and clinical and work productivity outcomes were categorized according to week-36 concordance category, defined as positive discordance (patient global assessment - physician global assessment ≥2), negative discordance (patient global assessment - physician global assessment ≤ -2), and concordance (absolute difference between the two disease activity assessments = 0 or 1). Correlations between discordance, clinical outcomes, and predictors of discordance were determined. At baseline, 520/762 (68.2 %) patient and physician global assessment scores were concordant, 194 (25.5 %) were positively discordant, and 48 (6.3 %) were negatively discordant. After 36 weeks of therapy, 556/763 (72.9 %) scores were concordant, 189 (24.8 %) were positively discordant, and 18 (2.4 %) were negatively discordant. Patients with week-36 concordance had the best 36-week clinical and patient-reported outcomes, and overall, the greatest improvement between baseline and week 36. Baseline pain, swollen joint count, duration of morning stiffness, fatigue, and patient general health significantly correlated with week-36 discordance, p < 0.0001 to p < 0.05. Additionally, baseline pain, patient general health, and C-reactive protein were predictors of week-36 discordance (odds ratios 1.22, 1

Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy

PubMed Central

Grisar, Johannes; Aletaha, Daniel; Steiner, Carl W; Kapral, Theresa; Steiner, Sabine; Säemann, Marcus; Schwarzinger, Ilse; Buranyi, Barbara; Steiner, Günter; Smolen, Josef S

2007-01-01

Objectives To study the effects of short‐term intermediate dose glucocorticoid (GC) therapy in patients with active rheumatoid arthritis (RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA. Methods EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF. Results After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 (SD 0.010)% (p<0.01), and from 12 (SD 4) to 27 (SD 7) CFU/well (p<0.02); CAC also increased from 7 (SD 2) to 29 (SD 8) cells/high power field (p<0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 (SD 10) to 14 (SD 6) pg/ml (p<0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU. Conclusions Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC. PMID:17293363

The effects of strength and endurance training in patients with rheumatoid arthritis.

PubMed

Strasser, Barbara; Leeb, Gunther; Strehblow, Christoph; Schobersberger, Wolfgang; Haber, Paul; Cauza, Edmund

2011-05-01

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.

Adenosine Deaminase activity and HLA-DRB as diagnostic markers for Rheumatoid Arthritis.

PubMed

Valadbeigi, Shirin; Ebrahimi-Rad, Mina; Khatami, Shohreh; Akhbari, Hadi; Saghiri, Reza

2018-04-05

Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine deaminase (ADA) isoenzymes could be useful and specific. The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases. Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive protein (CRP), rheumatoid factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*1,*04 and *010 was detected using PCR-SSP. ADA activity, particularly ADA2 level, was significantly higher among RA group (P<0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (P <0.05). The allele prevalence of DRB1*10 and *01 was significantly higher in RA patients (8.3% and 13.1%, respectively) compared with control group (2.51% and 5.5%, respectively) (P <0.05). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively. Increase tADA level and the frequency of DRB1*010 and *01 caused to susceptibility to RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis.

PubMed

Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra

2017-07-01

Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.

Periodontal Disease and Subgingival Microbiota as Contributors for RA Pathogenesis: Modifiable Risk Factors?

PubMed Central

Scher, Jose U.; Bretz, Walter A.; Abramson, Steven B.

2014-01-01

Purpose of review Since the early 1900s, the role of periodontal disease in the pathogenesis of rheumatoid arthritis has been a matter of intense research. The last decade has witnessed many advances supporting a link between periodontitis, the presence of specific bacterial species (i.e., Porphyromonas ginigivalis) and their effects in immune response. This review will examine available evidence on the subject. Recent findings Epidemiological studies have stressed the commonalities shared by periodontal disease and rheumatoid arthritis. Many groups have focused their attention towards understanding the periodontal microbiota and its alterations in states of health and disease. The presence of circulating antibodies against periodontopathic bacteria and associated inflammatory response has been found in both RA patients and subjects at-risk for disease development. Most recently, the periodontal microbiota of smokers and patients with RA has been elucidated, revealing profound changes in the bacterial communities compared to that of healthy controls. This has led to several small clinical trials of PD treatment as adjuvant for disease-modifying therapy in RA. Summary Smoking and periodontal disease are emerging risk factors for the development of RA. Epidemiological, clinical and basic research has further strengthened this association, pointing towards changes in the oral microbiota as possible contributors to systemic inflammation and arthritis. PMID:24807405

Lipids in RA: What do they mean?

PubMed Central

Plutzky, Jorge; Liao, Katherine P.

2018-01-01

In rheumatoid arthritis (RA), lipid levels are dynamic and can fluctuate along with changes in inflammation. A reduction in inflammation, most commonly as a result of disease modifying anti-rheumatic drug (DMARD) therapy, is associated with increases in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). A similar pattern of increased lipids is observed across biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs), suggesting that the main driver of changes in lipids is inflammation rather than individual treatments. In this review, we discuss new evidence shedding light on the potential mechanism underlying changes in lipid levels observed with changes in inflammation. Measured lipid levels in the blood are a result of a balance between synthesis and catabolism or absorption. Recent human studies in active RA show that the catabolic rates of lipids are higher than expected compared to expected rates in the general population. DMARD therapy appears to allow a return to baseline lower catabolic rates, resulting in an apparent increase in lipids. Additionally, we discuss findings from the recently published randomized controlled clinical trial, Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS). Findings from CANTOS provide further evidence for tighter control of inflammation to reduce cardiovascular risk in RA. PMID:29464513

The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.

PubMed

van Vollenhoven, Ronald F; Houbiers, Jos G A; Buttgereit, Frank; In 't Hout, Joanna; Boers, Maarten; Leij, Susanne; Kvien, Tore K; Dijkmans, Ben A C; Szczepański, Leszek; Szombati, Istvan; Sierakowski, Stanislaw; Miltenburg, André M M

2010-02-01

Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. The observed lack of clinical benefit in RA patients treated with an ERalpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERalpha-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.

Dissection of the FCGR3A association with RA: increased association in men and with autoantibody positive disease.

PubMed

Robinson, James I; Barrett, Jennifer H; Taylor, John C; Naven, Marc; Corscadden, Diane; Barton, Anne; Wilson, Anthony G; Emery, Paul; Isaacs, John D; Morgan, Ann W

2010-06-01

Genome-wide association studies in rheumatoid arthritis (RA) have failed to examine the FCGR gene cluster because of the confounding effects of segmental duplication. This study aimed to replicate previous candidate gene studies that had identified a significant association between the FCGR3A-158V allele and RA and then sought to estimate specific subgroup effects. FCGR3A-158F/V genotyping was undertaken in a UK Caucasian replication cohort comprising 2049 patients with RA and 1156 controls. Subgroup analyses assessing the magnitude of association according to gender and autoantibody (rheumatoid factor (RF) and cyclic citrullinated peptide (CCP)) status were undertaken in a pooled cohort of 2963 patients with RA and 1731 controls. Logistic regression was used to test for interaction between FCGR3A and HLA-DRB1 shared epitope (SE) alleles. In the combined RA cohort, borderline association with homozygosity was found for the FCGR3A-158V allele (OR 1.2, p=0.05), which was stronger in men (OR 1.7, p=0.01). Stratification by autoantibody status showed an increased risk in RF and CCP positive RA. Analysis of the FCGR3A-158V and HLA-DRB1 SE interaction revealed roles for both genes in susceptibility to autoantibody positive RA, with no evidence of interaction. FCGR3A is a risk factor for the development of autoantibody positive RA, particularly in men, with evidence of a multiplicative effect with HLA-DRB1 SE.

Cryotherapy decreases histamine levels in the blood of patients with rheumatoid arthritis.

PubMed

Wojtecka-Lukasik, E; Ksiezopolska-Orlowska, K; Gaszewska, E; Krasowicz-Towalska, O; Rzodkiewicz, P; Maslinska, D; Szukiewicz, D; Maslinski, S

2010-03-01

Conventional physiotherapy (electrotherapy, magnetic fields), kinesitherapy, and whole-body cryotherapy (plus kinesitherapy) are used to relieve pain and inflammation or to improve function in rheumatic diseases. The aim of this study was to investigate the effects of different physiotherapies and cryotherapy on biochemical blood parameters of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Twenty patients with RA and 17 patients with OA received whole-body cryotherapy at -140 to -160 degrees C for 2 to 3 min, once daily for 4 weeks. The second group of patients (24 with RA and 28 with OA) received conventional physiotherapy for 4 weeks. We measured the parameters of neutrophil activation (respiratory burst, calprotectin) and markers of cartilage metabolism [N-acetyl-beta-D-hexosaminidase (NAHase), ectonucleotide pyrophosphohydrolase (NTPPHase)] twice: before and 3 months after cryotherapy or physiotherapy. We showed, for the first time, that cryotherapy significantly reduced (P < 0.001) histamine levels in the blood of patients with RA. The effect was long-lasting (for at least 3 months). The levels of blood histamine in patients with OA were not changed significantly. Cryotherapy also downregulated the respiratory burst of PMNs and NAHase activity and upregulated calprotectin levels and the activity of NTPPHase. However, these changes were not statistically significant. In contrast, there were no significant changes in histamine levels or the other biochemical parameters measured in groups of patients treated only with physiotherapy and kinesitherapy. It may be concluded that the beneficial clinical effects of cryotherapy in RA patients are in part due to the action on the production, release, or degradation of histamine.

Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot study showing good tolerance, short-term improvement of pain and stiffness, and a trend towards long-term beneficial effects.

PubMed

Oosterveld, Fredrikus G J; Rasker, Johannes J; Floors, Mark; Landkroon, Robert; van Rennes, Bob; Zwijnenberg, Jan; van de Laar, Mart A F J; Koel, Gerard J

2009-01-01

To study the effects of infrared (IR) Sauna, a form of total-body hyperthermia in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients were treated for a 4-week period with a series of eight IR treatments. Seventeen RA patients and 17 AS patients were studied. IR was well tolerated, and no adverse effects were reported, no exacerbation of disease. Pain and stiffness decreased clinically, and improvements were statistically significant (p < 0.05 and p < 0.001 in RA and AS patients, respectively) during an IR session. Fatigue also decreased. Both RA and AS patients felt comfortable on average during and especially after treatment. In the RA and AS patients, pain, stiffness, and fatigue also showed clinical improvements during the 4-week treatment period, but these did not reach statistical significance. No relevant changes in disease activity scores were found, indicating no exacerbation of disease activity. In conclusion, infrared treatment has statistically significant short-term beneficial effects and clinically relevant period effects during treatment in RA and AS patients without enhancing disease activity. IR has good tolerability and no adverse effects.

Feel the Fatigue and Be Active Anyway: Physical Activity on High-Fatigue Days Protects Adults With Arthritis From Decrements in Same-Day Positive Mood.

PubMed

Hegarty, Rosisin S M; Conner, Tamlin S; Stebbings, Simon; Treharne, Gareth J

2015-09-01

The present study examined whether daily physical activity moderated the within-person relationship between daily fatigue and positive or negative mood in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Participants were 142 patients, 70 with RA and 72 with OA (67.6% women). Participants completed daily diaries during 4 fixed time windows per day for 7 days. Each diary assessed fatigue, pain, and positive and negative mood. Participants wore pedometers throughout each day and recorded pedometer readings at the end of each day. Physical activity buffered the same-day relationship between daily fatigue and positive mood for both RA and OA participants. On high-fatigue days, large decrements in mood were noted, but this was mitigated on days when participants were more physically active. Being more physically active on high-fatigue days buffered the negative effect of fatigue on positive mood among adults with both OA and RA. These findings have implications for understanding the daily variations in fatigue and inform potential clinical interventions. © 2015, American College of Rheumatology.

Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees

PubMed Central

Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

2013-01-01

An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl-β-D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4′-di-O-methyl aromadendrin (5), 4′-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β-carotene/linoleic acid tests. PMID:23935683

Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees.

PubMed

Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

2013-01-01

An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl- β -D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4'-di-O-methyl aromadendrin (5), 4'-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β -carotene/linoleic acid tests.

The Sophomore RA Experience: An Examination of Job Satisfaction, Turnover Intentions, and RA Self-Efficacy

ERIC Educational Resources Information Center

Brandt Brecheisen, Shannon M.

2014-01-01

The purpose of this national, quantitative study was to (1) provide psychometrics for the ACUHO-I/EBI RA Survey, a joint project between between Educational Benchmarking, Inc (EBI) and The Association of College and University Housing Officers--International (ACUHO-I), and (2) explore the sophomore resident assistant (RA) experience. This study…

Unexpected arterial wall and cellular inflammation in patients with rheumatoid arthritis in remission using biological therapy: a cross-sectional study.

PubMed

Bernelot Moens, Sophie J; van der Valk, Fleur M; Strang, Aart C; Kroon, Jeffrey; Smits, Loek P; Kneepkens, Eva L; Verberne, Hein J; van Buul, Jaap D; Nurmohamed, Michael T; Stroes, Erik S G

2016-05-21

Increasing numbers of patients (up to 40 %) with rheumatoid arthritis (RA) achieve remission, yet it remains to be elucidated whether this also normalizes their cardiovascular risk. Short-term treatment with TNF inhibitors lowers arterial wall inflammation, but not to levels of healthy controls. We investigated whether RA patients in long-term remission are characterized by normalized inflammatory activity of the arterial wall and if this is dependent on type of medication used (TNF-inhibitor versus nonbiological disease-modifying antirheumatic drugs (DMARDs)). Arterial wall inflammation, bone marrow and splenic activity (index of progenitor cell activity) was assessed with (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in RA patients in remission (disease activity score (DAS28) <2.6 for >6 months) and healthy controls. We performed ex vivo characterization of monocytes using flow cytometry and a transendothelial migration assay. Overall, arterial wall inflammation was comparable in RA patients (n = 23) in long-term remission and controls (n = 17). However, RA subjects using current anti-TNF therapy (n = 13, disease activity score 1.98[1.8-2.2]) have an almost 1.2-fold higher (18)F-FDG uptake in the arterial wall compared to those using DMARDs (but with previous anti-TNF therapy) (n = 10, disease activity score 2.24[1.3-2.5]), which seemed to be predominantly explained by longer duration of their rheumatic disease in a multivariate linear regression analysis. This coincided with increased expression of pro-adhesive (CCR2) and migratory (CD11c, CD18) surface markers on monocytes and a concomitant increased migratory capacity. Finally, we found increased activity in bone marrow and spleen in RA patients using anti-TNF therapy compared to those with DMARDs and controls. A subset of patients with RA in clinical remission have activated monocytes and increased inflammation in the arterial wall, despite the

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

PubMed

Pamuk, Ömer Nuri; Kalyoncu, Umut; Aksu, Kenan; Omma, Ahmet; Pehlivan, Yavuz; Çağatay, Yonca; Küçükşahin, Orhan; Dönmez, Salim; Çetin, Gözde Yıldırım; Mercan, Rıdvan; Bayındır, Özün; Çefle, Ayşe; Yıldız, Fatih; Balkarlı, Ayşe; Kılıç, Levent; Çakır, Necati; Kısacık, Bünyamin; Öksüz, Mustafa Ferhat; Çobankara, Veli; Onat, Ahmet Mesut; Sayarlıoğlu, Mehmet; Öztürk, Mehmet Akif; Pamuk, Gülsüm Emel; Akkoç, Nurullah

2016-07-01

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.