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Sample records for active ra patients

  1. Cumulative disease activity predicts incidental hearing impairment in patients with rheumatoid arthritis (RA).

    PubMed

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Rivera-Hoyos, Paula; Enríquez, Lorena; Ramírez-Anguiano, Jaqueline

    2014-03-01

    We previously reported that 24% of 113 rheumatoid arthritis (RA) patients had hearing impairment (HI). We investigated if disease activity was a predictor of incidental HI. One hundred and four patients completed three consecutive 6 months-apart rheumatic evaluations and concomitant audiometric evaluations which included at least an interview, an otoscopic evaluation, and a pure tone audiometry. HI was defined if the average thresholds for at least one of low-, mid-, or high-frequency ranges were ≥25 decibels (dB) hearing level in one or both ears. Appropriated statistics was used. Internal review board approval was obtained. Patients were most frequently middle-aged (43.4 ± 13.3 years), female (89.4%), and had median disease duration of 5 years and low disease activity. All were receiving RA treatment. At inclusion, 24 patients had HI which was sensorineural in 91.7% of them. Among the 80 patients without HI at baseline, 10 (12.5%) developed incidental HI, and they had more disease activity either at baseline ([median, range] disease activity score-28 joints evaluated-C-reactive protein [DAS28-CRP], 3.9 [1.6-7.3] vs. 2.1 [1-8.7], p = 0.006) or cumulative previous incidental HI (3.4 [1.8-4.8] vs. 2 [1-6.2], p = 0.007) and were more frequently on combined methotrexate and sulfasalazine (20 vs. 1.4%, p = 0.05) than their counterparts. In the adjusted Cox proportional model, cumulative DAS28-CRP was the only variable to predict incidental HI (odds ratio, 1.8; 95% confidence interval, 1.1-2.7; p = 0.01). Almost 13% of RA patients with short disease duration and low disease activity developed incidental HI during 1 year. Cumulative disease activity predicted incidental HI. PMID:24435352

  2. Cardiovascular risk factor management in patients with RA compared to matched non-RA patients

    PubMed Central

    Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P. M. H.; Liao, Katherine P.; Solomon, Daniel H.

    2016-01-01

    Objective. RA is associated with a 50–60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. PMID:26705329

  3. Assessment of global disease activity in RA patients monitored in the METEOR database: the patient's versus the rheumatologist's opinion.

    PubMed

    Gvozdenović, Emilia; Koevoets, Rosanne; Wolterbeek, Ron; van der Heijde, Désirée; Huizinga, Tom W J; Allaart, Cornelia F; Landewé, Robert B M

    2014-04-01

    The objectives of this study were to compare the patient's (PtGDA) and physician's (PhGDA) assessment of global disease activity and to identify factors that might influence these differences as well as factors that may influence the patient's and the physician's scores separately. Anonymous data were used from 2,117 Dutch patients included in the Measurement of efficacy of Treatment in the Era of Rheumatology database. PtGDA and PhGDA were scored independently on a 100-mm visual analog scale (VAS) with 0 and 100 as extremes. The agreement, intraclass correlation coefficients (ICC), was calculated and a Bland-Altman plot was created to visualize the differences between PtGDA and PhGDA. Linear mixed model analysis was used to model PtGDA and PhGDA. Logistic repeated measurements were used to model the difference in PtGDA and PhGDA (PtGDA > PhGDA versus PtGDA ≤ PhGDA). Gender patient, gender physician, age, swollen joint count (SJC), tender joint count, VAS pain, disease duration, and erythrocyte sedimentation rate (ESR) were considered as possible determinants in both models. Mean (standard deviation) age was 57 (15) years and 67 % of the patients were female. Agreement between PtGDA and PhGDA was moderate (ICC, 0.57). Patients scored on average 11 units higher (worse) than rheumatologists (95 % limits of agreement, -25.2 to 47.6). Patient's perception of pain (VAS) was positively associated with a PtGDA being higher than PhGDA. Similarly, ESR and swollen joint counts were positively associated with a PtGDA being lower or equal to the PhGDA. Patients rate global disease activity consistently higher than their rheumatologists. Patients base their judgment primarily on the level of pain, physicians on the level of SJC and ESR. PMID:24068385

  4. Clinical Response within 12 Weeks as a Predictor of Future Low Disease Activity in Early RA Patients: Results from the TEAR Trial

    PubMed Central

    Curtis, Jeffrey R; McVie, Theresa; Mikuls, Ted R; Reynolds, Richard J.; Navarro-Millán, Iris; O’Dell, James; Moreland, Larry W; Bridges, S. Louis; Ranganath, Veena K.; Cofield, Stacey S

    2013-01-01

    Background Rapidly predicting future outcomes based upon short-term clinical response would be helpful to optimize RA management in early disease. Objective To derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept (E) or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy. Methods Eligible subjects included in the derivation cohort (used for model building, n=186) were participants with moderate or higher disease activity (DAS28ESR>3.2) despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine+hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX+E or TT. Results The derivation cohort yielded three prediction models of varying complexity that included age, DAS28 at various time points, body mass index, and ESR (AUROC up to 0.83). Accuracy of the prediction models ranged between 80 and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and non-response. Approximately 80% of patients could be predicted to be responders or non-responders at week 12. Conclusion Clinical data collected early after starting or escalating DMARD/biologic treatment could accurately predict LDA at 1 year in early RA patients. For patients predicted to be non-responders, treatment could be changed at 12 weeks to optimize outcomes. PMID:23588939

  5. [Evaluation of joint inflammation by MRI in patients with RA].

    PubMed

    Sumida, Takayuki; Sugihara, Makoto; Hirota, Tomoya; Horikoshi, Masanobu; Suzuki, Takeshi

    2012-02-01

    We compared the characteristics of MRI imaging and US imaging on joint inflammation in patients with rheumatoid arthritis (RA) . MRI imaging is worth for diagnosis of RA at the early stage, evaluation of drug treatment effects, and a new measure for true remission. US imaging is also useful for estimation of therapy and a criteria for complete remission, and cheep machine. We hope that both imaging technologies will be a standard for diagnosis and therapy evaluation in RA patients. PMID:22298072

  6. The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA

    PubMed Central

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

    2012-01-01

    Objective: We studied the effect of stopping smoking on disease activity in patients with RA. Methods: Between 1992 and 2005, 2,800 adult 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), anti-CCP, general health and pain visual analog scales (VAS), EULAR response and treatment were registered at inclusion and at follow-up 2, 5 and 8 years. In 2010, a self-completion postal questionnaire was sent to 2,102 patients, enquiring about lifestyle factors, including cessation of smoking. Results: A total of 1,460 adult RA patients with disease duration ≤2 years were included in this study. Seventeen percent smoked in 2010. In total, 127 patients stopped smoking after inclusion in the study. Smoking cessation after inclusion in the study was negatively associated with EULAR good outcome at 8 years (OR 0.44, 95% CI 0.22–0.86, p=0.02), controlled for age, disease duration, sex, socioeconomic class, smoking status, RF, and DAS28 at inclusion. Conclusion: Seventeen percent of the RA patients smoked in 2010 in this large Swedish RA cohort. Stopping smoking after onset of RA did not change the poor prognosis of smokers with RA, but all RA patients need to stop smoking because of the high risk of cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA. PMID:23115602

  7. Anti-Citrullinated Protein Antibodies Induce Macrophage Subset Disequilibrium in RA Patients.

    PubMed

    Zhu, Wei; Li, Xiu; Fang, Shaohong; Zhang, Xiaoli; Wang, Ying; Zhang, Tongshuai; Li, Zhaoying; Xu, Yanwen; Qu, Siying; Liu, Chuanliang; Gao, Fei; Pan, Haile; Wang, Guangyou; Li, Hulun; Sun, Bo

    2015-12-01

    We used samples from rheumatoid arthritis (RA) patients to examine whether Anti-citrullinated protein antibodies (ACPAs) alter macrophage subset distribution and promote RA development. Macrophage subset distributions and interferon regulatory factor 4 (IRF4) and IRF5 expressions were analyzed. ACPAs were purified by affinity column. After RA and osteoarthritis (OA) patients' macrophages were cocultured with ACPAs, macrophage subsets and IRF4 and IRF5 expressions were measured. Small interfering RNAs (siRNAs) were transfected into ACPA-activated cells to suppress IRF4 or IRF5. Fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry were performed. Macrophage subset disequilibrium occurred in RA patient synovial fluids. IRF4 and IRF5 were all expressed in the synovial fluid and synovium. ACPAs (40 IU/ml) could induce macrophages to polarize to M1 subsets, and the percentage of increased M1/M2 ratio of RA patients was higher than that of the OA patients. ACPAs also induce IRF4 and IRF5 protein expressions. IRF5 siRNA transfection impaired ACPA activity significantly. We demonstrated that macrophage subset disequilibrium occurred in RA patients. ACPAs induced IRF5 activity and led to M1 macrophage polarization. PMID:26063186

  8. Do patients with active RA have differences in disease activity and perceptions if anti-TNF naïve versus anti-TNF experienced? Baseline results of the optimization of adalimumab trial

    PubMed Central

    Pope, Janet; Thorne, J. Carter; Haraoui, Boulos Paul; Psaradellis, Eliofotisti; Sampalis, John

    2012-01-01

    Summary Background The chance of a good response in RA is attenuated in previous anti-TNF users who start new anti-TNF therapy compared to biologic naïve patients. In active RA, those with previous anti-TNF exposure compared to anti-TNF naïve may have different baseline disease activity and patient perceptions when starting a new anti-TNF treatment that could explain the observed response differences. Material/Methods The aim of this study was a post hoc analysis of baseline characteristics of patients enrolled in the Optimization of Adalimumab study that was a treat to target vs. routine care study in patients initiating adalimumab. As per the protocol, a maximum of 20% anti-TNF experienced patients were enrolled in the 300 patient trial. Twelve (4.0%) were excluded who previously used other biologics. Baseline characteristics including age, gender, tender and swollen joint counts, disease activity (DAS28), function (HAQ-DI), patient global assessment, patient satisfaction with current treatment, and inflammatory markers (CRP, ESR), were compared between previously anti-TNF experienced [etanercept or infliximab (EXP)], and anti-TNF naïve patients (NAÏVE). Results The mean (SD) age was 54.8 (13.3) years; 81.0% were female, and 237 (79.0%) were anti-TNF naïve while 51 (17.0%) patients were anti-TNF experienced (29 with etanercept, 16 with infliximab, and 6 for both). The mean (SD) baseline in EXP versus NAÏVE groups respectively was: CRP=21.7(32.9) vs. 17.5(20.7); ESR=28.7(22.5) vs. 29.8(20.4); SJC=10.5(6.0) vs. 10.7(5.6); TJC=12.8(7.1) vs. 12.3(7.3); and DAS28=6.0(1.2) vs. 5.8(1.1). None of the between-group differences were statistically significant, however, the HAQ-DI in EXP was 1.7(0.6) compared to 1.5(0.7) for the NAÏVE (P=0.021). Additionally, EXP patients had a higher patient global score [71.3(26.1) vs. 61.9(26.2), P=0.021]. Conclusions Although anti-TNF naïve and experienced patients who initiated adalimumab were similar, with respect to several

  9. Radium content and the 226Ra /228Ra activity ratio in groundwater from bedrock

    NASA Astrophysics Data System (ADS)

    Asikainen, Matti

    1981-08-01

    The relative abundance of 226Ra and 228Ra were determined in the groundwater from 125 drilled wells containing from < 0.1 to 51.3 pCi/l of 226Ra. The determination of 228Ra was carried out with a liquid scintillation counter by measuring only the weakly energetic β particles emitted from 228Ra. Thus the interference from the daughter nuclides of 226Ra was avoided, without specific separation of 228Ac. The direct measurement of 228Ra made the method decisively simpler and faster in terms of the chemistry involved. The concentration of 228Ra was found to be independent of the amount of 226Ra present in the samples. The concentrations of 228Ra were nearly the same over the whole range of 226Ra concentrations and the average sol 226Ra /228Ra ratio sharply increased as the 226Ra content of water increased. The 226Ra /228Ra ratio in the drilled wells varied from 0.3 to 26. Abnormally high 226Ra /228Ra ratios were found in areas with known uranium deposits as well as in several drilled wells at other locations. The abnormally high 226Ra /228Ra ratios present in groundwater suggest that the radioactivity anomaly is caused by uranium deposits and not by common rocks. In samples with a low radioactivity level the average 226Ra /228Ra ratio was slightly below unity, corresponding to the typical U/ Th ratio of granite, the most common kind of rock in the study area. The samples from the rapakivi area proved to be exceptional in that they had a low 226Ra /228Ra ratio independent of the concentration of 226Ra.

  10. 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.

  11. Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking water using a single sample preparation procedure.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail P

    2005-12-01

    The current federal and New Jersey State regulations have greatly increased the number of gross alpha and radium tests for public and private drinking water supplies. The determination of radium isotopes in water generally involves lengthy and complicated processes. In this study, a new approach is presented for the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water samples. The method includes a single sample preparation procedure followed by alpha counting and gamma-ray spectroscopy. The sample preparation technique incorporates an EPA-approved co-precipitation methodology for gross alpha determination with a few alterations and improvements. Using 3-L aliquots of sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle activity of the sample is measured with a low-background gas-flow proportional counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the sample are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is required, the gamma-ray counting should be performed within 2-4 d from sample collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy can be repeated 21 d after sample preparation to ensure that 226Ra and its progeny have reached the equilibrium state. At this point, the 228Ac equilibration with parent 228Ra is already established. Analysis of aliquots of de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra standards demonstrated the accuracy and precision of this method. Various performance evaluation samples were also assayed for gross alpha as well as radium isotope activity determination using this procedure and the

  12. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  13. An experimental analysis of the contribution of 224Ra and 226Ra and progeny to the gross alpha-particle activity of water samples.

    PubMed

    Arndt, Michael F; West, Lynn E

    2008-05-01

    The gross alpha-particle activity of water samples analyzed by EPA Method 900.0 is investigated as a function of residue mass and geometry, time between sample collection and analysis, and time between sample preparation and analysis for samples containing 224Ra, 212Pb, and 226Ra. It is shown that the gross alpha-particle activity due to 224Ra and its progeny can be up to 10 times the 224Ra activity at collection time and that due to 212Pb progeny can be up to 3 times the 212Pb activity at collection time. In samples with roughly equal activities of 224Ra and 226Ra analyzed soon after collection, it is shown that the gross alpha-particle activity is approximately constant with time because the decay of 224Ra and its progeny is offset by the ingrowth of 226Ra progeny. PMID:18403967

  14. 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

  15. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA Study

    PubMed Central

    Sokka, Tuulikki; Toloza, Sergio; Cutolo, Maurizio; Kautiainen, Hannu; Makinen, Heidi; Gogus, Feride; Skakic, Vlado; Badsha, Humeira; Peets, Tõnu; Baranauskaite, Asta; Géher, Pál; Újfalussy, Ilona; Skopouli, Fotini N; Mavrommati, Maria; Alten, Rieke; Pohl, Christof; Sibilia, Jean; Stancati, Andrea; Salaffi, Fausto; Romanowski, Wojciech; Zarowny-Wierzbinska, Danuta; Henrohn, Dan; Bresnihan, Barry; Minnock, Patricia; Knudsen, Lene Surland; Jacobs, Johannes WG; Calvo-Alen, Jaime; Lazovskis, Juris; Pinheiro, Geraldo da Rocha Castelar; Karateev, Dmitry; Andersone, Daina; Rexhepi, Sylejman; Yazici, Yusuf; Pincus, Theodore

    2009-01-01

    Introduction Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). Methods The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. Results Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but

  16. A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients

    PubMed Central

    Hölscher, Christoph; Heitmann, Lisa; Owusu-Dabo, Ellis; Horstmann, Rolf D.; Meyer, Christian G.; Ehlers, Stefan; Thye, Thorsten

    2016-01-01

    The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4Rα subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4Rα. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13/IL-4Rα-dependent mechanisms are involved in mediating tissue pathology of human TB. PMID:26977119

  17. Opium Addiction Increases Interleukin 1 Receptor Antagonist (IL-1Ra) in the Coronary Artery Disease Patients

    PubMed Central

    Saadat, Habibollah; Ziai, Seyed Ali; Ghanemnia, Maryam; Namazi, Mohammad Hasan; Safi, Morteza; Vakili, Hosein; Dabbagh, Ali; Gholami, Omid

    2012-01-01

    Background There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response. Purpose To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients. Methods The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test. Results IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes. Conclusion Consumption of opium in CAD patients is associated with higher IL-1Ra levels. PMID:23028694

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

    SciTech Connect

    Yu Zengli . E-mail: yuzengli@263.net; Xing Ying . E-mail: xingy@zzu.edu.cn

    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 of 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.

  19. (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...

  20. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

    PubMed Central

    Gonzalez-Montoya, Norma Guadalupe; Gamez-Nava, Jorge I.; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. PMID:24454473

  1. PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

    PubMed

    Zavala-Cerna, Maria Guadalupe; Gonzalez-Montoya, Norma Guadalupe; Nava, Arnulfo; Gamez-Nava, Jorge I; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Gonzalez-Lopez, Laura; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. PMID:24454473

  2. 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

  3. The impact of social support on the acceptance process among RA patients: a qualitative study.

    PubMed

    Kostova, Zlatina; Caiata-Zufferey, Maria; Schulz, Peter J

    2014-01-01

    Acceptance is an important component of pain management, being associated with improved quality of life and lower levels of pain and depression. In enabling patients with chronic diseases to accept unpleasant consequences and to establish a new way of living, the support they receive from their social environment may play a decisive role. In this article, we identify the key sources and types of social support that are relevant for rheumatoid arthritis (RA) patients, and explore when and how those sources are important across the different stages of the acceptance process. We conducted a qualitative study involving 20 semi-structured interviews with RA patients in Switzerland. Analysis of the data followed the precepts of grounded theory. We found that, amid the complexity and variety of patients' struggles for acceptance, there were some common experiences or 'key moments' in which social support played an important role. While three sources of support - family, physicians and the external social context - are fundamental for RA patients, all three may inhibit as well as encourage acceptance, due to the invisible and unpredictable character of the disease. There is a pervasive risk either of underestimating patients' suffering or of over-supporting, both of which prevent patients accepting the disease and developing a new 'normal' life. We conclude that sources of social support need to find a middle way between scepticism and solicitousness. PMID:24841727

  4. Debilitating diarrhoea and weight loss due to colitis in two RA patients treated with leflunomide.

    PubMed

    Verschueren, P; Vandooren, A K; Westhovens, R

    2005-02-01

    Diarrhoea and weight loss are frequently reported adverse events in rheumatoid arthritis (RA) patients receiving the disease-modifying antirheumatic drug (DMARD) leflunomide. According to the available literature these side effects occur mostly during the first 6 months of treatment, are rather mild and rarely lead to treatment withdrawal. In this report, we describe the clinical, endoscopic and histologic findings in two RA patients with severe diarrhoea and important weight loss more than 12 months after starting treatment with leflunomide. In both cases the symptoms were caused by colitis, but one had ulcerative and the other microscopic colitis. Despite treatment with budesonide the complaints only improved after withdrawal of leflunomide, making a causal relationship between this drug and the pathogenesis of colitis probable. The heterogeneous histopathological findings in these two patients, however, do not allow us to draw any definitive conclusions about the mechanism by which leflunomide causes diarrhoea and weight loss in RA patients. We conclude that persistent diarrhoea or weight loss in patients taking leflunomide can be more serious than what is previously reported in the literature. In such cases leflunomide treatment should be stopped and an endoscopic examination of the colon is recommended. Given the long half-life of this drug a washout procedure with cholestyramine should be considered whenever the problem is severe or persistent. PMID:15565393

  5. Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Wang, Weiwei; Shan, Jianping; Lin, Fujun; Jiang, Gengru; Yang, Yuan H.; Wang, Die; Xu, Dakang; Shen, Lisong

    2012-01-01

    Background The role of naturally occurring regulatory T cells (Treg) in the control of the development of systemic lupus erythematosus (SLE) has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4+FoxP3+ T cells into subpopulations during the dynamic SLE development. Methodlogy/Principal Findings To evaluate the proliferative and suppressive capacities of different CD4+ T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA+FoxP3low naive Treg cells (nTreg cells) and CD45RA−FoxP3low (non-Treg) cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA+FoxP3low nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI) and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25+CD45RA+ can be used to defined CD45RA+FoxP3low nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA+FoxP3low nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. Conclusions/Significance Our results indicate that impaired numbers of functional CD45RA+FoxP3low naive Treg cell and CD45RA−FoxP3low non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3+ T cells, using a combination of FoxP3, CD25 and CD

  6. Measurement of 224Ra uptake in a fern actively accumulating radium.

    PubMed

    Chao, J H; Lee, H P; Chiu, C Y

    2006-03-01

    A method is proposed for determining the level of 224Ra in plant samples by measuring its descendant nuclide 212Pb at 239 keV by gamma-ray spectrometry. Variations of 224Ra and 212Pb over time during sample preparation and counting were delineated prior to gamma-ray measurement. The 224Ra concentrations in plant samples were measured by their direct uptake from soil, which could be determined and distinguished from that resulting from decay of 228Th inside the plants. We propose that a field-growing Dicranopteris linearis, which actively accumulates radium, can be used as an indicator of the nutritional transportation and metabolic rate of radium and other alkaline earth elements. We investigated the influence of rainfall on 224Ra concentrations in fronds of D. linearis and the corresponding uptake rates. 224Ra could serve as a natural tracer of growth in plants over a several days. Its presence and content in plants implies a temporal mineral metabolic rate, which can provide useful information for plant physiological and environmental investigations. PMID:16087212

  7. Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells.

    PubMed

    Pathak, Janak L; Verschueren, Patrick; Lems, Willem F; Bravenboer, Nathalie; Klein-Nulend, Jenneke; Bakker, Astrid D; Luyten, Frank P

    2016-05-01

    Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors. Serum was obtained from 15 patients with active RA (active RA-sera) and from the same patients in clinical remission 1 year later (remission RA-sera; controls). The effect of active RA-sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary human periosteum-derived progenitor cells (HPDC) was determined in micromass culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40% and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels by 16%, and matrix mineralization by 17% at day 21 compared with remission RA-sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9 transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7 compared with remission RA-sera. In conclusion, sera from patients with active RA negatively affect differentiation of osteochondrogenic precursors, and as a consequence may contribute to delayed fracture healing in these patients. PMID:27050327

  8. Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

    PubMed

    Valor, Lara; Martínez-Estupiñán, Lina; Janta, Iustina; Nieto, Juan Carlos; Ovalles-Bonilla, Juan Gabriel; González-Fernández, Carlos; Del Rio, Tamara; Hernández-Flórez, Diana; Monteagudo, Indalecio; López-Longo, Francisco Javier; Naredo, Esperanza

    2016-06-01

    This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count. PMID:27072348

  9. 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

  10. Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127low Treg Cells in Patients With Chronic Rheumatoid Arthritis

    PubMed Central

    Walter, Gina J.; Fleskens, Veerle; Frederiksen, Klaus S.; Rajasekhar, Megha; Menon, Bina; Gerwien, Jens G.; Evans, Hayley G.

    2015-01-01

    Objective Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA. Methods Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127low Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte‐derived cytokine/chemokine production, and gene expression profiles. Results No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin‐17 [IL‐17], interferon‐γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL‐1β, IL‐1 receptor antagonist, IL‐7, CCL3, or CCL4) by autologous lipopolysaccharide‐activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL‐6, IL‐8, IL‐12, IL‐15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls. Conclusion Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in

  11. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry.

    PubMed

    van Beek, P; Souhaut, M; Reyss, J-L

    2010-07-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes. PMID:20106569

  12. Prolong Exposure of NSAID in Patients With RA Will Decrease the Risk of Dementia: A Nationwide Population-Based Cohort Study.

    PubMed

    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

    2016-03-01

    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

  13. 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…

  14. Infliximab treatment reduces complement activation in patients with rheumatoid arthritis

    PubMed Central

    Familian, A; Voskuyl, A; van Mierlo, G J; Heijst, H; Twisk, J; Dijkmans, B; Hack, C

    2005-01-01

    Background: Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA. Objective: To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA. Methods: 35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time. Results: At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment. Conclusion: Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA. PMID:15958758

  15. 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. PMID:25805536

  16. 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 Central

    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

    Objective 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. Methods 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. Results 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. Conclusions 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. Trial registration number NCT00578305 PMID:25355728

  17. 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

  18. 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. PMID:23935683

  19. Time‐dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists

    PubMed Central

    Askling, Johan; Fored, C Michael; Brandt, Lena; Baecklund, Eva; Bertilsson, Lennart; Feltelius, Nils; Cöster, Lars; Geborek, Pierre; Jacobsson, Lennart T; Lindblad, Staffan; Lysholm, Jörgen; Rantapää‐Dahlqvist, Solbritt; Saxne, Tore; van Vollenhoven, Ronald F; Klareskog, Lars

    2007-01-01

    Objectives The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. Methods First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross‐referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co‐morbidity and use of inpatient care into account. Results Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person‐years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. Conclusion Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration. PMID:17261532

  20. In Patients with Established RA, Positive Effects of a Randomised Three Month WBV Therapy Intervention on Functional Ability, Bone Mineral Density and Fatigue Are Sustained for up to Six Months

    PubMed Central

    Prioreschi, Alessandra; Makda, Mohamed A.; Tikly, Mohammed; McVeigh, Joanne A.

    2016-01-01

    Functional ability is often impaired for people with rheumatoid arthritis (RA), rendering these patients highly sedentary. Additionally, patients with RA often take medication known to negatively affect bone mass. Thus improving functional ability and bone health in this group of patients is important. The aim of this study was to investigate the effects of whole body vibration (WBV) therapy in patients with stable, established RA. Thirty one females with RA were randomly assigned to a control group (CON, n = 15) who continued with their normal activities or a WBV group (n = 16) who underwent a three month WBV therapy intervention, consisting of 15 minutes of intermittent vibration, performed twice per week. Patients were assessed at baseline, three months, and three months post intervention for functional ability using the modified Health Assessment Questionnaire; for RA disease activity using the Clinical Disease Activity Index, for quality of life using self-report fatigue and pain scores; for physical activity profiles using accelerometry, and for BMD and body composition using DXA. Patients in both groups were matched for all variables at baseline. After the intervention period, functional ability was significantly improved in the WBV group (1.22(0.19) to 0.92(0.19), p = 0.02). Hip BMD was significantly reduced in the CON group (0.97(0.05) to 0.84(0.05) g.cm-2, p = 0.01), while no decreases were seen in the WBV group (1.01(0.05) to 0.94(0.05) g.cm-2, p = 0.50). Despite no change in RA disease activity in either group at either follow up, fatigue levels were improved in the WBV group (4.4(0.63) to 1.1(0.65), yet remained unchanged in the CON group at both follow ups (p = 0.01). Ten minute bouts of light to moderate physical activity were significantly reduced in the CON group after the intervention (2.8(0.61) to 1.8(0.64) bouts per day, p = 0.01), and were preserved in the WBV group (3.1(0.59) to 3.0(0.61) bouts per day, p = 0.70). Intermittent WBV shows

  1. Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs.

    PubMed

    Kapetanovic, Meliha Crnkic; Roseman, Carmen; Jönsson, Göran; Truedsson, Lennart

    2011-12-01

    The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR. PMID:21956234

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

    PubMed Central

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

    2016-01-01

    Introduction 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. Aim 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. Materials and Methods 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. Results 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. Conclusion 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. PMID:27134854

  3. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    PubMed

    Minnock, Patricia; Veale, Douglas J; Bresnihan, Barry; FitzGerald, Oliver; McKee, Gabrielle

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0-33); 6.9 ± 8.9 (0-33)), more recent and current pain intensity (41.4 ± 26.6 (0-80) 24.4 ± 26.6 (0-100) and depression (11.8 ± 7.5 (1-35); 8.2 ± 6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue. PMID:26453249

  4. Resistance of CD45RA- T cells to apoptosis and functional impairment, and activation of tumor-antigen specific T cells during radiation therapy of prostate cancer.

    PubMed

    Tabi, Zsuzsanna; Spary, Lisa K; Coleman, Sharon; Clayton, Aled; Mason, Malcolm D; Staffurth, John

    2010-07-15

    The effect of radiation therapy (RT) to the pelvis on circulating T cells was studied in prostate cancer (PCa) patients to provide a baseline for a more informed design of combination radioimmunotherapy. Peripheral blood samples taken from 12 PCa patients with locally advanced tumor before, during, and after hypofractionated RT were analyzed for T cell phenotype and function. There was significantly more loss of naive and early memory compared with more differentiated T cells during RT. The proportions of annexin-V(+) and Fas-expressing T cells were elevated in patients during RT and in PBMC irradiated in vitro (< or = 5.0 Gy), with preferential increases in CD45RA(+) T cells. The baseline level of apoptosis of CD45RA(-) T cells increased > 2-fold in the presence of an IkappaB-kinase inhibitor, indicating a protective effect via this pathway. T cell proliferation was impaired during RT with IL-2-dependent recovery post-RT. Recall T cell responses to common viral Ags, measured by IFN-gamma production, were little affected by RT. In vitro irradiation of healthy donor PBMCs resulted in a significantly increased frequency of responding T cells, due at least partly to the preferential elimination of CD45RA(+) T cells. Most importantly, antitumor CD4(+) and CD8(+) T cell responses were detectable after, but not before or during RT. The results indicate that generating tumor-specific T cell responses before RT and boosting their activity post-RT are ways likely to amplify the frequency and function of antitumor T cells, with implications for scheduling immunotherapy in PCa. PMID:20548027

  5. Determining the Lowest Optimally Effective Methotrexate Dose for Individual RA Patients Using Their Dose Response Relation in a Tight Control Treatment Approach

    PubMed Central

    Nair, Sandhya C.; Jacobs, Johannes W. G.; Bakker, Marije F.; Jahangier, Z. Nazira; Bijlsma, Johannes W. J.; van Laar, Jacobs M.; Lafeber, Floris P. J. G.; Welsing, Paco M. J.

    2016-01-01

    Objective To determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted. Methods Data from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment strategy in early RA was used. For each patient a curve for disease activity over time was fitted and the MTX dose after which further step-up did not result in relevant improvement in disease activity anymore was determined the 'lowest optimally effective MTX dose (LOED)'. The association of demographic and clinical characteristics at baseline with this LOED and with the level of disease activity reached at LOED was studied. Results In 204 (100 MTX and 104 MTX with prednisone) out of 236 patients LOED could be defined. 10 mg/wk was the most prevalent LOED in patients treated with MTX and prednisone and 10 mg/wk, 20 mg/wk and 30 mg/wk in the MTX strategy. Although the specific LOED could not reliably be predicted, higher baseline disease activity, height and lower weight were associated with higher LOEDs (i.e at least 15 mg/wk). A score was presented to decide on a starting dose of 10 mg/wk or (at least) 15 mg/wk. The level of disease activity at LOED could not be reliably predicted. Conclusion A starting dose of 10 mg/wk might be a good choice for most patients and is frequently already the optimal dose. However, a subgroup of patient can be determined who would require higher MTX doses. PMID:26987073

  6. Activity standardisation of ²²⁶Ra by 4πα liquid scintillation counting method.

    PubMed

    Havelka, Miroslav; Bluďovský, Richard

    2013-11-01

    Activity of (226)Ra in radium daughter products free solution was determined by 4πα liquid scintillation counting (LSC) method, where the detection efficiency of radium decay is practically equal to 1. The sources were prepared from solution with known (226)Ra mass concentration, from which, immediately before LS counting, (222)Rn and its daughter nuclides were removed by solvent extraction. LS counting results were corrected practically only for a <0.6% loss of radium from measured sample and for the ingrowth of (222)Rn and (218)Po concentrations in the sample after the separation was completed. The combined relative standard uncertainty was estimated to be lower than 0.34%. PMID:23602705

  7. Activity ratios of (234)U/(238)U and (226)Ra/(228)Ra for transport mechanisms of elevated uranium in alluvial aquifers of groundwater in south-western (SW) Punjab, India.

    PubMed

    Kumar, A; Karpe, R K; Rout, S; Gautam, Y P; Mishra, M K; Ravi, P M; Tripathi, R M

    2016-01-01

    The concentrations of total dissolved uranium (U), its isotopic composition ((234)U, (235)U, (238)U) and two long lived Ra isotopes ((226)Ra and (228)Ra) in alluvial aquifers of groundwater were determined to investigate the groundwater flow pattern in the south-western (SW) Punjab, India. Particular attention was given to the spatial variability of activity ratios (ARs) of (234)U/(238)U and (226)Ra/(228)Ra to predict the possible sources and supply process of U into the water from the solid phase. The measured groundwater (234)U/(238)U ARs were ∼1 or >1 in the shallow zone (depth < 30 m) with high U concentration and <1 in the deeper zone (depth > 30 m) with relatively low U concentration. The simultaneous elevated U concentration and (234)U/(238)U ARs in waters were possibly due to differences in imprints of rock-water interactions under hydrologic conditions. However, (234)U/(238)U ARs < 1 clearly indicate the lack of recharge from surface water to groundwater leading to (234)U deficit in groundwater. This deficit might be also attributed to alpha recoil processes under strong dissolution. Overall, the decreasing pattern of (234)U/(238)U ARs observed from SE to SW or NW ward clearly indicates a groundwater flow paths from SE to SW/NW. Similarly, (226)Ra/(238)U ARs < 1 for all water samples reflect that the precursor (238)U is fairly mobile relative to (226)Ra. This might be due to unusually high amount of (238)U in groundwaters and subsequently the different geochemistry of the two isotopes. On the other hand, (226)Ra/(228)Ra ARs in groundwaters varied widely and observed about 50-300 times higher than (238)U/(232)Th ARs in granitic rocks or soils. Such elevation in ARs might be attributed to different dissolution properties of their parents during water-rock interactions or lattice damage during decay or local enrichments of uranium in the aquifers. PMID:26555366

  8. Draft genome sequence of Xanthomonas axonopodis pv. glycines 8ra possessing transcription activator-like effectors used for genetic engineering.

    PubMed

    Lee, Ju-Hoon; Shin, Hakdong; Park, Hye-Jee; Ryu, Sangryeol; Han, Sang-Wook

    2014-06-10

    Xanthomonas axonopodis pv. glycines 8ra is a causal agent of bacterial pustule disease in soybean. This bacterium possesses transcription activator-like (TAL) effectors which are useful for genetic/protein engineering applications in higher organisms including plants and humans. Here, we report that the draft genome sequence consists of 5,337,885-bp double-stranded DNA encoding 4674 open reading frames (ORFs) in 13 different contigs. This genome sequence would be useful in applications of TAL effectors in genetic engineering and in elucidating virulence factors against plants. PMID:24657734

  9. Anti-hnRNP B1 (RA33) Autoantibodies Are Associated with the Clinical Phenotype in Russian Patients with Rheumatoid Arthritis and Systemic Sclerosis

    PubMed Central

    Maslyanskiy, Aleksey; Lazareva, Natalya; Olinek, Polina; Schierack, Peter; Cuccato, Juliane; Bogdanos, Dimitrios P.; Lapin, Sergey V.

    2014-01-01

    Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS), in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%; P < 0.001). In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5%) patients with RA, 6/58 (10.3%) SPA, 11/65 (16.9%) SSc, and 4/50 (8.0%) SLE. In RA patients, anti-hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels and erythrocyte sedimentation rate, while in patients with SSc it was associated with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical characteristics in patients with RA and SSc. PMID:24883333

  10. 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. PMID:27405025

  11. The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in Rheumatoid Arthritis: Data from BARFOT, a Multi-Centre Study of Early RA

    PubMed Central

    Andersson, Maria L.E.; Bergman, Stefan; Söderlin, Maria K.

    2013-01-01

    Background: There have been no reports on the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. Methods: Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR) response criteria were registered. In 2010, 1,430 patients completed a questionnaire enquiring about demographics and lifestyle factors. Results: One hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28 (5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000), VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs 8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ, for up to 8 years of follow-up). Immigrant status did not have any effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have any effect on treatment or outcome. Conclusions: Immigrants scored worse in pain, function and TJC for up to 2 years of follow-up, but they did not differ from non-immigrants in objective measures of inflammation or EULAR outcome. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class had no effect on treatment or outcome, and this could be due to the relatively egalitarian society in Sweden. PMID:24358069

  12. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    PubMed

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities. PMID:25301826

  13. Phenotype transition of CD4{sup +} T cells from CD45RA to CD45RO is accompanied by cell activation and proliferation

    SciTech Connect

    Johannisson, A.; Festin, R.

    1995-04-01

    An investigation of proliferation and activation events in subsets of human CD4{sup +} cells, defined by their expression of CD45RA and CD45RO, is reported. A single-laser based assay for the study of multiple surface antigens and two-parameter cell cycle analysis was used for sorting of and subsequent analysis of proliferation in CD4{sup +}CD45RA{sup +}CD45RO{sup {minus}}, CD4{sup +}CD45RA{sup {minus}}CD45RO{sup +} subsets and phenotypically intermediate stages. After labelling with BrdUrd, cells were sorted with flow cytometry on the basis of light-scattering properties and staining with anti-CD45RA, anti-CD45RO, and anti-CD4 markers. Sorted cells were double stained with anti-BrdUrd-antibodies and PI, and the frequencies of proliferating cells were determined. After 48 h, the highest rate of proliferation was found among cells with a phenotype intermediate between CD4{sup +}CD45RA{sup +}CD45RO{sup {minus}} and CD4{sup +}CD45RA{sup {minus}}CD45RO{sup +}. After 72 h of culture, the situation was changed insofar as the point of highest proliferation had shifted towards the CD4{sup +}CD45RA{sup {minus}}CD45RO{sup +} population. These findings were further corroborated by four-color staining with anti-CD4, anti-CD45RA, anti-CD45RO, and Hoechst 33342. This indicates that the phenotype transition is accompanied by cell proliferation. The correlated temporal expression of antigens related to activation (HLA-DR, CD25, CD69, CD71) and cell adhesion (CD11a, CD54, L-selectin) in each of the different subsets was also investigated. All the activation markers CD25, CD69, and CD71 show a more heterogeneous pattern of expression among the CD4{sup +} CD45RA{sup {minus}}CD45RO{sup +} cells than the CD4{sup +} CD45RA{sup +}CD45RO{sup {minus}} cells, indicating a subpopulation of CD4{sup +}CD45RA{sup {minus}}CD45RO{sup +} cells responding more slowly to the mitogenic stimulation. 32 refs., 8 figs.

  14. Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Andrés Cerezo, Lucie; Kuklová, Markéta; Hulejová, Hana; Vernerová, Zdeňka; Kaspříková, Nikola; Veigl, David; Pavelka, Karel; Vencovský, Jiří; Šenolt, Ladislav

    2015-01-01

    Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA. PMID:26339140

  15. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  16. Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with disease activity in patients with rheumatoid arthritis

    PubMed Central

    2011-01-01

    Introduction Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA). Methods Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis. Results Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte

  17. 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. PMID:22606910

  18. Evaluation of differences in HLA-DR4 gene and its subtypes prevalence among healthy people and RA patients in Isfahan province population

    PubMed Central

    Salesi, Mansour; Boroujeni, Golshan Taghipour; Salehi, Mansoor; Farzamnia, Somaieh

    2016-01-01

    Background: There are a lot of evidences showing that genetic play an important role in RA disease. Inheritance of some subgroups of HLA-DR4 gene increases the propensity to RA disease. In this paper, the impact of HLA-DR4 gene and its subtypes or subgroups, be consistence on RA patient who lived in Isfahan province, has been evaluated. Materials and Methods: In this survey, two groups of people (100 patients in case group and 100 normal persons in control group) have been selected. These two groups were similar in age and gender. Statistical population has been considered among people who visited Al Zahra rheumatology clinic. The participants were from Isfahan province and accepted to participate to the study voluntarily. The prevalence of HLA-DR4 and its 0401-0404 subtypes were evaluated between two groups; DNA was extracted from blood samples and studied using PCR SSCP method. Results: It was found that 35% of RA patients had HLA-DR4 gene, of which 14 persons had 0401, 10 persons had 0404, and 11 persons had other subtypes, whereas 30 people in control group had HLA-DR4 gene, of which 10 people had 0401, 20 people had 0404, and nobody had other subtypes. Conclusion: The observed differences between prevalence of HLA-DR4 gene between the case and control group were not statistically significant (P = 0.45; OR = 1.256; 95% CI = 0.69-2.27), but a relation was between HLA-DR4 0404 subtypes and RA (P = 0.02; OR = 0.44; 95% CI = 0.196-0.992). PMID:26962513

  19. Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients

    PubMed Central

    Rodenburg, R.; van den Hoogen, F. H J; Barrera, P.; van Venrooij, W. J; van de Putte, L. B A

    1999-01-01

    OBJECTIVE—Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels.
METHODS—Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1β (IL1β), IL8, and α2 macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).
RESULTS—Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1β and α2 macroglobulin mRNAs.
CONCLUSION—These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.

 PMID:10491366

  20. Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices.

    PubMed

    Hegazy, M; Darwish, H; Darweesh, H; El-Shehaby, A; Emad, Y

    2010-04-01

    The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p=0.003 and p < or = 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r=0.486 and p=0.001), BILAG musculoskeletal score (r=0.848 and p < or = 0.001) and BILAG cardiorespiratory score (r=0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE. PMID:20116334

  1. Effects of copper supplementation on erythrocyte superoxide dismutase activity levels in rheumatoid arthritis patients

    SciTech Connect

    Marten, J.T.; DiSilvestro, R.A. )

    1989-02-09

    Rheumatoid arthritis (RA) patients are reported to possess lower than normal levels of Cu-Zn superoxide dismutase (SOD) activity. The contribution of copper status to these low values has not been examined. To address this issue, blood samples were obtained from 10 RA patients before and after 28 days of daily oral copper supplementation (2 mg/day). All patients were receiving gold therapy. Each RA subject, before supplementation, displayed lower erythrocyte SOD values than any of 25 age matched controls. The mean value for the RA subjects was about 40% lower than the control mean, whether expressed as units per ml packed cells or per mg hemoglobin. Erythrocyte SOD activity levels were increased in all subjects by the 4 week copper supplementation, with 7 of the patients showing at least a 22% increase. Presupplement SOD activities showed no correlation with serum C-reactive protein contents, an indicator of acute phase response. Serum levels of the copper containing acute phase protein ceruloplasmin, showed variable responses to copper supplementation. The studies described here are currently being extended to include RA subjects not being treated with gold and to include supplemented controls.

  2. TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression.

    PubMed

    Wagner, Josef; Skinner, Narelle A; Catto-Smith, Anthony G; Cameron, Donald J S; Michalski, Wojtek P; Visvanathan, Kumar; Kirkwood, Carl D

    2013-08-01

    Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated in the pathogenesis of Crohn's disease (CD). The role of CD susceptibility genes in association with these microbes is not known. Sixty-two early onset paediatric CD patients and 46 controls with known MAP status were analysed for an association with 34 single nucleotide polymorphisms (SNPs) from 18 CD susceptibility genes. Functional studies on peripheral blood mononuclear cells (PBMCs) were conducted on 17 CD patients with known CD mutations to assess IL-6, IL-10, and TNF-α expression upon stimulation with MAP precipitated protein derivative (PPD) and lipopolysaccharide (LPS). In addition, surface expression of IL10R and TLR4 on resting B cells, NK cells, T cells, and monocytes was assessed. A mutation in TLR4 (rs4986790) and IL10RA (rs22291130) was significantly associated with MAP-positive CD patients compared to MAP-negative CD patients (27.6 vs. 6.1 %, p = 0.021, and 62.1 vs. 33.3 %, p = 0.024, respectively). PPD and LPS significantly increased IL-6, IL-10, and TNF-α production in PBMCs. IL-10 and TNF-α production were significantly lower in a subgroup of CD patients (5/12) with a known NOD2 mutation. Receptor for IL-10 was significantly higher expressed on NK cells (CD56low) and on NK T cells harbouring a NOD2 mutations compared to wildtype cells (p = 0.031 and 0.005, respectively). TLR4 was significantly higher expressed on NK cells (CD56high) harbouring a NOD2 mutations compared to wildtype cells (p = 0.038). PMID:23455702

  3. Determination of ²²⁶Ra, ²²⁸Ra and ²¹⁰Pb in NORM products from oil and gas exploration: problems in activity underestimation due to the presence of metals and self-absorption of photons.

    PubMed

    Landsberger, S; Brabec, C; Canion, B; Hashem, J; Lu, C; Millsap, D; George, G

    2013-11-01

    Typical calibration of solid environmental samples for the determination of (226)Ra, (228)Ra and (210)Pb entails the use of standard reference materials which have a very similar matrix. However, TENORM samples from the oil and gas exploration contain unusually high amounts of calcium, strontium and barium which can severely attenuate the photons of (210)Pb and (226)Ra with their characteristic 46.1 keV and 186.2 keV gamma-rays, respectively and to some extent (228)Ra with the characteristic gamma-rays of 911.2 keV and 969.0 keV. We used neutron activation analysis to evaluate the content of TENORM for calcium, barium and strontium and then used a software program SELABS to determine the self-absorption. Our results confirm that even in Petrie containers with small dimensions the (210)Pb can be underestimated by almost by a factor of four while (226)Ra can be underestimated by 5%. The (228)Ra activities are virtually unaffected due to the higher energy gamma-rays. However, the implications for TENORM studies that employ large Marinelli containers having sample sizes between 0.25 and 1.0 L may be severely compromised by the presence of high Z elements in elevated concentrations. The usual spectral interferences on (226)Ra, (228)Ra and (210)Pb coming from other radionuclides in the (234)U, (235)U and (238)U decay chains are virtually nonexistent due the very high activity levels of (226)Ra, (228)Ra and (210)Pb in the tens of thousands of Bq/kg. PMID:23514714

  4. 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

  5. IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.

    PubMed

    Ortiz, M A; Diaz-Torné, C; Hernández, M V; Reina, D; de la Fuente, D; Castellví, I; Moya, P; Ruiz, J M; Corominas, H; Zamora, C; Cantó, E; Sanmartí, R; Juarez, C; Vidal, S

    2015-06-01

    Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24weeks of treatment, percentages of IFNγ-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status. PMID:25847223

  6. Correlations between IL-2 enhancing activity and clinical parameters in patients with rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Tomura, K; Kang, H; Mitamura, K; Takei, M; Yamagami, K; Karasaki, M; Nishinarita, S; Hayama, T; Sawada, S; Horie, T

    1991-04-01

    In a previous paper (Tomura, K. et al. Tohoku J. Exp. Med., 1989, 159, 171-183), we discovered IL-2 enhancing factor(s) designated B cell derived-growth enhancing factor-2 (BGEF-2), which enhanced IL-2 dependent cell proliferation, and reported that BGEF-2 was produced by B cells of the patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) only when they were in the active stage of the disease. In this paper, we studied relationship between each IL-2 enhancing activity from B cell supernatant of the patients with these diseases and clinical parameters. IL-2 enhancing activities did not correlate with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), but correlated with plasma concentrations of gamma-globulin from the patients with RA and SLE in the active stages. IL-2 enhancing activities correlated with hypocomplementemia and leukocytopenia in the patients with SLE, and also correlated with RAHA titer in the patients with RA. Moreover, on several patients with RA or SLE in the active stages, diminution of IL-2 enhancing activity was found when they were in the remission stage after treatments. These findings suggested that IL-2 enhancing activity (i.e., BGEF-2 activity) correlated with activity of these diseases and supported the hypothesis that BGEF-2 played an important role in the polyclonal B cell activation and autoantibody production in patients with these diseases. PMID:1715616

  7. The Challenge and Opportunity of Capturing Patient Reported Measures of Rheumatoid Arthritis Disease Activity in Vulnerable Populations with Limited Health Literacy and Limited English Proficiency.

    PubMed

    Hirsh, Joel M

    2016-05-01

    Limited health literacy and limited English proficiency are widely prevalent and contribute to rheumatoid arthritis (RA) health care disparities. The RA Patient Global Assessment of Disease Activity often introduces complexity to the health care encounters of patients and research subjects with limited health literacy and limited English proficiency. Important work is being done to ensure that patient-reported outcomes are validated and appropriate for diverse and vulnerable populations. PMID:27133494

  8. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.

    PubMed

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI. PMID:27035669

  9. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection

    PubMed Central

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg–Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk’s lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg–Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI. PMID:27035669

  10. 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. PMID:26219268

  11. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    PubMed Central

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  12. Asymptomatic Atherosclerosis in Egyptian Rheumatoid Arthritis Patients and Its Relation to Disease Activity

    PubMed Central

    Elshereef, Rawhya R.; Darwish, Aymen; Ali, Amal; Abdel-kadar, Mohammed; Hamdy, Lamiaa

    2015-01-01

    Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls (P = 0.003**). A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease (P = 0.0001***) and patient's age (P = 0.01*). There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients. PMID:25737726

  13. The tetraspanin CD9 is preferentially expressed on the human CD4+CD45RA+ naive T cell population and is involved in T cell activation

    PubMed Central

    KOBAYASHI, H; HOSONO, O; IWATA, S; KAWASAKI, H; KUWANA, M; TANAKA, H; DANG, N H; MORIMOTO, C

    2004-01-01

    Human CD4+ T cells can be divided into reciprocal memory and naive T cell subsets based on their expression of CD45 isoforms and CD29/integrin beta1 subunit. To identify unique cell surface molecules on human T cells, we developed a new monoclonal antibody termed anti5H9. Binding of anti5H9 triggers a co-stimulatory response in human peripheral blood T cells. Retrovirus-mediated expression cloning has revealed that the antigen recognized by anti5H9 is identical to the tetraspanin CD9. We now show that human CD9 is preferentially expressed on the CD4+CD45RA+ naive T cell subset, and that CD9+CD45RA+ T cells respond preferentially to the recombinant beta2-glycoprotein I, compared to CD9–CD45RA+ T cells. Furthermore, anti5H9 inhibits both the recombinant beta2-glycoprotein I- and the recall antigen tetanus toxoid-specific T cell proliferation. These results suggest that the tetraspanin CD9 plays an important role in T cell activation. PMID:15196249

  14. Deletion of mtrC in Haemophilus ducreyi Increases Sensitivity to Human Antimicrobial Peptides and Activates the CpxRA Regulon ▿

    PubMed Central

    Rinker, Sherri D.; Trombley, Michael P.; Gu, Xiaoping; Fortney, Kate R.; Bauer, Margaret E.

    2011-01-01

    Haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance in H. ducreyi. We found a proton motive force-dependent effect on H. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC rendered H. ducreyi more sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. The mtrC mutant 35000HPmtrC exhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type by trans-complementation with mtrC. Similar phenotypes were reported in a cpxA mutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. A cpxR mutant had wild-type levels of antimicrobial peptide resistance; a cpxA mutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrC was more sensitive than the cpxA mutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrC had lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism in H. ducreyi and shows that LL-37 resistance in H. ducreyi is multifactorial. PMID:21444663

  15. Preparation of (228)Ra standard solution.

    PubMed

    Havelka, Miroslav

    2016-03-01

    For the preparation of a standard solution of (228)Ra, (228)Ra was isolated from (232)Th salt. Two simple methods were developed for Th-Ra separation. Both are based on a very good solubility of thorium nitrate in organic solvents. The first one used Ra co-precipitation with Pb in the form of Pb(NO3)2 from acetic acid solution. The second method was based on solvent extraction, remaining Th in the organic phase, while Ra was concentrated in the aqueous phase. The activity of (228)Ra (up to 20kBq) in the standard solution was related to the (232)Th standard by means of gamma ray spectrometry measurement. The obtained uncertainty was less than 0.7% (k=1). The standard solution was free of (232)Th and contained the carrier in the usual concentration (1gL(-1) BaCl2, 10gL(-1) HCl). PMID:26651171

  16. High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

    PubMed Central

    Wang, J; Shan, Y; Jiang, Z; Feng, J; Li, C; Ma, L; Jiang, Y

    2013-01-01

    This study aimed to examine the frequency of different subsets of circulating B and T follicular helper (Tfh) cells in patients with new-onset rheumatoid arthritis (RA) and following standard therapies. Twenty-five RA patients and 15 healthy controls (HC) were recruited for characterizing the frequency of CD27+, immunoglobulin (Ig)D+, CD86+, CD95+, Toll-like receptor (TLR)-9+ B cells and inducible T cell co-stimulator (ICOS) and programmed death 1 (PD-1)-positive Tfh cells and the level of serum interleukin (IL)-21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD+CD27−CD19+ naive B, CD86+CD19+ and CD95+CD19+ activated B, CD3+CD4+CXCR5+, CD3+CD4+CXCR5+ICOS+, CD3+CD4+CXCR5+PD-1+ and CD3+CD4+CXCR5+ICOS+PD-1+ Tfh cells but lower IgD+CD27+CD19+ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL-21 in the RA patients. Furthermore, the percentages of CD95+ B cells were correlated positively with the frequency of PD-1+ Tfh cells, but negatively with ICOS+ Tfh cells. The percentages of CD86+ B cells and ICOS+ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages of CD86+ B and PD-1+ Tfh cells were reduced significantly in the drug-responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA. PMID:23786438

  17. Non-destructive determination of 224Ra, 226Ra and 228Ra concentrations in drinking water by gamma spectroscopy.

    PubMed

    Parekh, Pravin; Haines, Douglas; Bari, Abdul; Torres, Miguel

    2003-11-01

    The U.S. Environmental Protection Agency mandates that drinking water showing gross alpha-activity greater than 0.19 Bq L(-1) should be analyzed for radium, a known human carcinogen. The recommended testing methods are intricate and laborious. The method reported in this paper is a direct, non-destructive gamma-spectroscopic method for the determination of 224Ra, 226Ra, and 228Ra, the three radium isotopes of environmental concern in drinking water. Large-volume Marinelli beakers (4.1-L capacity), especially designed for measuring radioactive gases, in conjunction with a low-background, high-efficiency (131%) germanium detector were used in this work. It was first established that radon, the gaseous decay product of radium, and its progeny are quantitatively retained in this Marinelli beaker. The 224Ra, 226Ra, and 228Ra activity concentrations are determined from the equilibrium activities of their progeny: 212Pb, 214Pb (214Bi), and 228Ac; and the gamma-lines used in the analysis are 238.6, 351.9 (and 609.2), and 911.2 keV, respectively. The 224Ra activity is determined from the first 1,000-min measurement performed after expulsion of radon from the sample. The 226Ra activity is determined from the second, 2,400-min measurement, made 3 to 5 d later, and the 228Ra activity is determined from either the first or the second measurement, depending on its concentration level. The method's minimum detectable activities are 0.017 Bq L(-1), 0.020 Bq L(-1), and 0.027 Bq L(-1) for 224Ra, 226Ra, and 228Ra, respectively, when measured under radioactive equilibrium. These limits are well within the National Primary Drinking Water Regulations required limit of 0.037 Bq L(-1) for 226Ra and for 228Ra. The precision and accuracy of the method, evaluated using the U.S. Environmental Protection Agency and the Environmental Resource Associates' quality control samples, were found to be within acceptable limits. PMID:14571995

  18. In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells

    SciTech Connect

    Baadsgaard, O.; Salvo, B.; Mannie, A.; Dass, B.; Fox, D.A.; Cooper, K.D. )

    1990-11-01

    In vivo UV exposure of human epidermis abrogates the function of CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages. Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+ (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure in humans leads to a T cell response in which suppression dominates. Autologous blood T cells were incubated with epidermal cell suspensions from in vivo UV-irradiated skin. After activation, repurified T cells were transferred in graded numbers to autologous mononuclear cells (MNC) stimulated with PWM and the resultant IgG production analyzed by ELISA. Relative to T cells activated by unirradiated control epidermal cells, T cells activated by UV-exposed epidermal cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV-exposed epidermal cells could be directly activated to suppress PWM-stimulated MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive activity was also transferable with purified CD4+ T cells stimulated by UV-exposed epidermal cells (n = 10; p less than or equal to 0.01), and was radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal cells, suggesting indirect induction of CD8+ Ts cells contained within the responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted in total abrogation of the suppressor function contained in the CD4+ T cells. Activation of suppressor function was critically dependent on DR+ APC contained in UV-exposed epidermis.

  19. 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. PMID:22407780

  20. "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…

  1. Martin RA-30 Baltimore

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Martin RA-30 Baltimore: The Martin RA-30 Baltimore was a light bomber ordered by the Royal Air Force. Some examples were retained in the United States as part of a 'Reverse Lend-Lease.' This example was flown by the NACA from June 1943 until March 1944.

  2. Determination of 226Ra and 224Ra in drinking waters by liquid scintillation counting.

    PubMed

    Manjón, G; Vioque, I; Moreno, H; García-Tenorio, R; García-León, M

    1997-04-01

    A method for the determination of Ra-isotopes in water samples has been developed. Ra is coprecipitated with Ba as sulphate. The precipitate is then dissolved with EDTA and counted with a liquid scintillation system after mixing with a scintillation cocktail. The study of the temporal evolution of the separated activity gives the isotopic composition of the sample, i.e. the 224Ra and 226Ra contribution to the total activity. The method has been applied to some Spanish drinking waters. PMID:9106993

  3. Synergistic activation of retinoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor {alpha} (RAR{alpha})-, RAR{beta}-, or RAR{gamma}-selective ligand in combination with retinoid Z receptor-specific ligand

    SciTech Connect

    Roy, B.; Taneja, R.; Chambon, P.

    1995-12-01

    This research indicates thatn retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers activate transcription of RA-responsive genes and induce cell differentiation of P19 and F9 cells in a ligand-dependent manner. 43 refs., 4 figs., 2 tabs.

  4. Vertical Profiles Of {sup 226}Ra, {sup 232}Th And {sup 40}K Activities In Rocks From The Irati Formation Of The Parana Sedimentary Basin, Southern Brazil

    SciTech Connect

    Ferreira, Ademar de O.; Bastos, Rodrigo O.; Appoloni, Carlos R.

    2008-08-07

    Naturally occurring radioisotopes are present in different concentrations in sedimentary rocks, reflecting the origin of the sediments, the depositional environment, and more recent events such as weathering and erosion. Using a high-resolution {gamma}-ray spectrometry methodology, sedimentary rocks were measured to assess the concentration activities of the natural radioisotopes. The surveyed rocks are from the Irati formation in the Parana sedimentary basin, which are exposed by an abandoned, open-pit limestone mine, in the city of Sapopema, southern Brazil. The exposed vertical profile is 5 m, and its stratigraphy is represented by an alternation of limestone and bituminous shale (layers being a few decimeters thick), and some millimeter rhythm layers with limestone and bituminous shale laminas. Eleven samples were collected along this profile, each of them dried in the open air during 48 hours, sieved through 4 mm mesh and sealed in cylindrical recipients. Measurements were accomplished using a 66% relative efficiency HPGE detector connected to a standard gamma ray spectrometry electronic chain. The detector efficiency in the range of 60 to 1800 keV was carried out with the certified IAEA-385 sediment sample. The Lower Limit of Detection (LLD) to the system is 2.40 Bq{center_dot}kg{sup -1} for {sup 226}Ra, 1.84 Bq{center_dot}kg{sup -1} for {sup 232}Th and 4.20 Bq{center_dot}kg{sup -1} for {sup 40}K. Activity concentrations were determined for {sup 226}Ra (from 16.22 to 151.55 Bq{center_dot}kg{sup -1}), {sup 232}Th (from 2.93 to 56.12 Bq{center_dot}kg{sup -1}) and {sup 40}K (from 38.45 to 644.63 Bq{center_dot}kg{sup -1}). The layers enriched with organic matter presented the higher values of activity. The measured concentrations of the natural radioisotopes were lower for limestone samples (average values and respective deviations were 22.81{+-}0.22 Bq{center_dot}kg{sup -1} for {sup 226}Ra, 4.21{+-}0.07 Bq{center_dot}kg{sup -1} for {sup 232}Th, and 50

  5. Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis.

    PubMed Central

    Duarte, R; Kindlelán, J M; Carracedo, J; Sánchez-Guijo, P; Ramírez, R

    1997-01-01

    Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that resembles that of superantigens from alpha/beta T cells. After culture in vitro with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T lymphocytes from ACF-TBC patients occurs in a range similar to that observed in healthy subjects. Following activation, H37Ra-stimulated gamma/delta T lymphocytes from healthy subjects did proliferate in the presence of exogenous recombinant human interleukin 2. However, under the same conditions, gamma/delta T lymphocytes from ACF-TBC patients not only did not proliferate but died by apoptosis. These results suggest that in gamma/delta T lymphocytes from patients with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads to apoptotic cell death. PMID:9008275

  6. Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment.

    PubMed

    Skoumal, M; Haberhauer, G; Feyertag, J; Kittl, E M; Bauer, K; Dunky, A

    2006-09-01

    To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II-IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2-10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA. PMID:16485108

  7. Phospholipid base exchange activity in the leukocyte membranes of patients with inflammatory disorders.

    PubMed Central

    Niwa, Y.; Sakane, T.; Ozaki, Y.; Kanoh, T.; Taniguchi, S.

    1987-01-01

    Phospholipid base exchange and cholinephosphotransferase (CPT) and ethanolaminephosphotransferase (EPT) activities were assessed in the membranes of neutrophils or lymphocytes from patients with various inflammatory disorders. Ethanolamine exchange activity was significantly enhanced in both neutrophils and lymphocytes from patients with active Behçet's disease, active systemic lupus erythematosus (SLE), and severe bacterial infections and slightly enhanced in those from patients with active rheumatoid arthritis (RA), compared with healthy controls. No abnormal findings were found in CPT, EPT, or serine or choline base exchange activities in the leukocytes from any of the diseased groups tested or in the ethanolamine exchange activity of patients with severe viral infections and inactive SLE, RA, and Behçet's disease. The authors have recently demonstrated the enhancement of transmethylation and phospholipase A2 activity in human leukocyte membranes at the height of inflammatory disease states, as well as the activation of leukocyte ethanolamine exchange by bioactive stimulants. These data postulate that phosphatidylethanolamine synthesis by the base exchange reaction may be the precursor of transmethylation and its subsequent activation of phospholipase A2, leading to the induction of arachidonic acid cascade. PMID:3034067

  8. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

    PubMed Central

    van Onna, M; Ten Cate, D F; Tsoi, K L; Meier, A J L; Jacobs, J W G; Westgeest, A A A; Meijer, P B L; van Beek, M C; Rensen, W H J; Bijlsma, J W J

    2016-01-01

    Objectives In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. Methods In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. Results At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. Conclusions In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA. PMID:26452538

  9. Error-control and processes optimization of (223/224)Ra measurement using Delayed Coincidence Counter (RaDeCC).

    PubMed

    Xiaoqing, Cheng; Lixin, Yi; Lingling, Liu; Guoqiang, Tang; Zhidong, Wang

    2015-11-01

    RaDeCC has proved to be a precise and standard way to measure (224)Ra and (223)Ra in water samples and successfully made radium a tracer of several environmental processes. In this paper, the relative errors of (224)Ra and (223)Ra measurement in water samples via a Radium Delayed Coincidence Count system are analyzed through performing coincidence correction calculations and error propagation. The calculated relative errors range of 2.6% ∼ 10.6% for (224)Ra and 9.6% ∼ 14.2% for (223)Ra. For different radium activities, effects of decay days and counting time on final radium relative errors are evaluated and the results show that these relative errors can decrease by adjusting the two measurement factors. Finally, to minimize propagated errors in Radium activity, a set of optimized RaDeCC measurement parameters are proposed. PMID:26233651

  10. The estimation and potential radiobiological significance of the intake of 228Ra by early Ra dial workers in Illinois.

    PubMed

    Keane, A T; Lucas, H F; Markun, F; Essling, M A; Holtzman, R B

    1986-09-01

    We made radiochemical determinations of 226Ra and the 228Ra-decay product, 228Th, in samples of bone from former Ra dial workers who belonged to a major cohort of Ra-exposed persons under study for health effects at our institution. Most of the former workers were long-term residents of two communities supplied with drinking water containing elevated natural levels of 228Ra and 226Ra, so determinations also were made of radioactivity in samples of bone from long-term residents not occupationally exposed to Ra. The 228Th activity of the bones of the former workers, after correction for the presence of natural radioactivity, showed that some had significant occupational intakes of 228Ra, contrary to published reports that 228Ra was never used by the Illinois company that had employed the cohort of early workers. For 14 workers hired in the years 1920-23, the calculated ratio of the occupational intake of 228Ra to 226Ra activity averaged 0.15 (coefficient of variation 0.65), whereas for three workers hired in 1924, it was not significantly different from zero (mean 0.05, coefficient of variation 1.5). The risk of radiogenic cancer for the typical worker hired before 1924 may have been nearly twice that incurred in the absence of the 228Ra component of the Ra intakes. PMID:3744831

  11. 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

  12. Measurement of 226Ra, 232Th, 137Cs and 40K activities of Wheat and Corn Products in Ilam Province – Iran and Resultant Annual Ingestion Radiation Dose

    PubMed Central

    CHANGIZI, Vahid; SHAFIEI, Elham; ZAREH, Mohammad Reza

    2013-01-01

    Background: Background: Natural background radiation is the main source of human exposure to radioactive material. Soils naturally have radioactive mineral contents. The aim of this study is to determine natural (238 U, 232 Th, 40 K) and artificial (137 Cs) radioactivity levels in wheat and corn fields of Eilam province. Methods: HPGe detector was used to measure the concentration activity of 238 U and 232 Th series, 40 K and 137 Cs in wheat and corn samples taken from different regions of Eilam province, in Iran. Results: In wheat and corn samples, the average activity concentrations of 226 Ra, 232 Th, 40 K and 137 Cs were found to be 1, 67, 0.5, 91.73, 0.01 and 0.81, 0.85, 101.52, 0.07 Bq/kg (dry weight), respectively. H ex and H in in the present work are lower than 1. The average value of H ex was found to be 0.02 and 0.025 and average value of H in to be found 0.025 and 0.027 in wheat fields samples and corn samples in Eilam provinces, respectively. The obtained values of AGDE are 30.49 mSv/yr for wheat filed samples and 37.89 mSv/yr for corn samples; the AEDE rate values are 5.28 mSv/yr in wheat filed samples and this average value was found to be 6.13 mSv/yr in corn samples in Eilam. Transfer factors (TFs) of long lived radionuclide such as 137 Cs, 226 Ra, 232 Th and 40 K from soils to corn and wheat plants have been studied by radiotracer experiments. Conclusion: The natural radioactivity levels in Eilam province are not at the range of high risk of morbidity and are under international standards. PMID:26056646

  13. Activity concentrations of 226Ra, 232Th, 40K and 137Cs radionuclides in Turkish medicinal herbs, their ingestion doses and cancer risks

    NASA Astrophysics Data System (ADS)

    Parmaksız, Aydın; Ağuş, Yusuf

    2014-11-01

    Twenty-two medicinal herb samples, each representing a distinct species, were collected from Turkish markets and measured by the gamma spectrometric method. The activity concentration of 226Ra in medicinal herbs was found in the range of minimum detectable activity (MDA) and 15.1 ± 2.2 Bqkg-1. The activity concentration of 232Th ranged from MDA values to 3.5 ± 0.8 Bqkg-1. The activity concentration of 40K varied between 50.0 ± 16.8 and 1311.5 ± 57.3 Bqkg-1. All 137Cs activity concentrations of medicinal herbs were found to have lower than MDA values. The bone surface dose, lower large intestine and colon doses were found to be 182.9, 18.8 and 18.7 µSvy-1, respectively. The highest committed effective dose originated from the annual ingestion of 1 kg medicinal herb was calculated notably low as 9.0 µSv. The cancer risk of ingestion of medicinal herbs was found to be small enough to be neglected. The selected Turkish medicinal herbs are considered safe for human consumption.

  14. Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept

    PubMed Central

    Kanbe, Katsuaki; Oh, Koei; Chiba, Junji; Inoue, Yasuo; Taguchi, Masashi; Yabuki, Akiko

    2016-01-01

    The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept. PMID:27103846

  15. The association of body mass index with disease activity and clinical response to combination therapy in patients with rheumatoid arthritis

    PubMed Central

    Mirpourian, Maryam; Salesi, Mansour; Abdolahi, Hadi; Farajzadegan, Ziba; Karimzadeh, Hadi

    2014-01-01

    Background: The role of obesity in clinical curse of rheumatoid arthritis (RA) is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. Materials and Methods: Active RA patients with the disease activity score using 28 joint counts (DAS28) > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI) and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week) plus hydroxychloroquine (200 to 400 mg/day) and prednisolone (2.5 to 10 mg/day) and were followed by DAS28 for up to 24 weeks. Results: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001) after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = –0.415, P = 0.005) and waist circumference (r = –0.296, P = 0.05) were correlated with baseline DAS28. Although BMI (r = –0.337, P = 0.025) and waist circumference (r = –0.315, P = 0.038) were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. Conclusion: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients. PMID:25197291

  16. Leukocyte Activation in Obese Patients

    PubMed Central

    Minervino, Daniele; Gumiero, Daniela; Nicolazzi, Maria Anna; Carnicelli, Annamaria; Fuorlo, Mariella; Guidone, Caterina; Di Gennaro, Leonardo; Fattorossi, Andrea; Mingrone, Geltrude; Landolfi, Raffaele

    2015-01-01

    Abstract The rising prevalence of obesity is a major global health problem. In severe obesity, bariatric surgery (BS) allows to obtain a significant weight loss and comorbidities improvement, among them one of the factors is the thrombotic risk. In this observational study, we measured indices of leukocyte activation in severely obese patients as markers of increased thrombotic risk in relation with serum markers of inflammation before and after BS. Frequency of polymorphonuclear neutrophil-platelet (PLT) and monocyte (MONO)-PLT aggregates as well as of tissue factor (TF) expressing MONOs was measured in the peripheral blood of 58 consecutive obese patients and 30 healthy controls. In 31 of the 58 obese patients, data obtained at the enrollment were compared with those obtained at 3, 6, and 12 months after BS. Compared with healthy controls, obese patients showed a higher frequency of polymorphonuclear leukocyte (PMNL)-PLT aggregates (7.47 ± 2.45 [6.82–8.11]% vs 5.85 ± 1.89 [5.14–6.55]%, P = 0.001), MONO-PLT aggregates (12.31 ± 7.33 [10.38–14.24]% vs 8.14 ± 2.22 [7.31–8.97]%, P < 0.001), and TF expressing MONOs (4.01 ± 2.11 [3.45–4.56]% vs 2.64 ± 1.65 [2.02–3.25]%, P = 0.002). PMNL-PLT and MONO-PLT aggregate frequency was positively correlated with TF expressing MONOs (R2 = 0.260, P = 0.049 and R2 = 0.318, P = 0.015, respectively). BS was performed in 31 patients and induced a significant reduction of the body mass index, and waist and hip circumferences. These effects were associated with a significant decrease of PMNL-PLT aggregates at 12 months (7.58 ± 2.27 [6.75–8.42]% vs 4.47 ± 1.11 [3.93–5.01]%, P < 0.001), and a reduction of TF expressing MONOs at 6 (3.82 ± 2.04 [3.07–4.57]% vs 1.60 ± 1.69 [0.30–2.90]%, P = 0.008) and 12 months (3.82 ± 2.04 [3.07–4.57]% vs 1.71 ± 0.54 [1.45–1.97]%, P = 0.001) after BS. These data suggest that leukocyte

  17. An improved method for the simultaneous determination of /sup 224/Ra, /sup 226/Ra and /sup 228/Ra in water, soils and sediments

    SciTech Connect

    Lucas, H.F.

    1987-01-01

    The naturally occurring concentrations of radium (/sup 226/Ra and /sup 228/Ra) in public and private water supplies have been studied for many years. Both general surveys ad local studies have established the geographical regions where well waters exceed 3 pCi/L (1-17). In general, the /sup 226/Ra was determined by the emanation method, while the /sup 228/Ra was determined from the beta activity of the /sup 228/Ac daughter. In a recent review (18) of the methods used ''a number of approved analytic methods can bear improvement, especially the method for 228Ra.'' The purpose of the work described here was to develop an improved method for the simultaneous determination of /sup 226/Ra and /sup 228/Ra. 22 refs., 3 tabs.

  18. 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.

  19. Silibinin Improves the Effects of Methotrexate in Patients with Active Rheumatoid Arthritis: Pilot Clinical Study

    PubMed Central

    Hussain, Saad Abdulrahman; Mortada, Ahmed Hashem; Jasim, Nazar Abdulateef; Gorial, Faiq Isho

    2016-01-01

    Objectives Our study sought to evaluate the effects of silibinin in patients with active rheumatoid arthritis (RA) treated with methotrexate (MTX). Methods We conducted a randomized multi-center, double-blind, placebo-controlled clinical trial over a 16-week treatment period at the Al-Sader and Baghdad Teaching Hospitals in Najaf and Baghdad, respectively. A total of 60 patients (30 of each sex) with active RA, already maintained on 12 mg MTX weekly for at least three consecutive months, were included in the study. Patients were randomly allocated to receive either 120 mg silibinin twice daily or a placebo, combined with their regular MTX regimen. The patients were evaluated by measuring disease activity score using the 28-joint Disease Activity Score, Simple Disease Activity Index, and Health Assessment Questionnaire–Disability Index scores at the start and end of the study. Blood samples were evaluated for the erythrocyte sedimentation rate (ESR), hemoglobin (Hb), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK), anti-cyclic citrullinated peptide (CCP), and the serum cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, and IL-2. Results Silibinin significantly decreases the already elevated clinical scores compared to placebo treatment. ESR, IL-8, IL-6, TNF-α, anti-CCP, hs-CRP levels were significantly reduced. Additionally, the use of silibinin significantly increases Hb, IL-10, and IL-2 levels. Conclusion Silibinin may improve the effects of MTX on certain biochemical and clinical markers of patients with active RA. PMID:27403238

  20. Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

    PubMed

    Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu

    2016-06-01

    The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD. PMID:27072347

  1. Establishing a Core Domain Set to Measure Rheumatoid Arthritis Flares: Report of the OMERACT 11 RA Flare Workshop

    PubMed Central

    Bykerk, Vivian P.; Lie, Elisabeth; Bartlett, Susan J.; Alten, Rieke; Boonen, Annelies; Christensen, Robin; Furst, Daniel E.; Hewlett, Sarah; Leong, Amye L.; Lyddiatt, Anne; March, Lyn; May, James E.; Montie, Pam; Orbai, Ana-Maria; Pohl, Christoph; Voshaar, Marieke Scholte; Woodworth, Thasia; Bingham, Clifton O.; Choy, Ernest H.

    2015-01-01

    Objective The OMERACT Rheumatoid Arthritis (RA) Flare Group (FG) is developing a data-driven, patient-inclusive, consensus-based RA flare definition for use in clinical trials, longterm observational studies, and clinical practice. At OMERACT 11, we sought endorsement of a proposed core domain set to measure RA flare. Methods Patient and healthcare professional (HCP) qualitative studies, focus groups, and literature review, followed by patient and HCP Delphi exercises including combined Delphi consensus at Outcome Measures in Rheumatology 10 (OMERACT 10), identified potential domains to measure flare. At OMERACT 11, breakout groups discussed key domains and instruments to measure them, and proposed a research agenda. Patients were active research partners in all focus groups and domain identification activities. Processes for domain selection and patient partner involvement were case studies for OMERACT Filter 2.0 methodology. Results A pre-meeting combined Delphi exercise for defining flare identified 9 domains as important (> 70% consensus from patients or HCP). Four new patient-reported domains beyond those included in the RA disease activity core set were proposed for inclusion (fatigue, participation, stiffness, and self-management). The RA FG developed preliminary flare questions (PFQ) to measure domains. In combined plenary voting sessions, OMERACT 11 attendees endorsed the proposed RA core set to measure flare with ≥ 78% consensus and the addition of 3 additional domains to the research agenda for OMERACT 12. Conclusion At OMERACT 11, a core domain set to measure RA flare was ratified and endorsed by attendees. Domain validation aligning with Filter 2.0 is ongoing in new randomized controlled clinical trials and longitudinal observational studies using existing and new instruments including a set of PFQ. PMID:24584927

  2. 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

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

    1995-12-01

    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

  3. 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.

  4. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment

    PubMed Central

    Rech, Juergen; Hueber, Axel J; Finzel, Stephanie; Englbrecht, Matthias; Haschka, Judith; Manger, Bernhard; Kleyer, Arnd; Reiser, Michaela; Cobra, Jayme Fogagnolo; Figueiredo, Camille; Tony, Hans-Peter; Kleinert, Stefan; Wendler, Joerg; Schuch, Florian; Ronneberger, Monika; Feuchtenberger, Martin; Fleck, Martin; Manger, Karin; Ochs, Wolfgang; Schmitt-Haendle, Matthias; Lorenz, Hanns-Martin; Nuesslein, Hubert; Alten, Rieke; Henes, Joerg; Krueger, Klaus; Schett, Georg

    2016-01-01

    Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. Trial registration number EudraCT 2009-015740-42. PMID:26483255

  5. Patient Acceptable Symptom State in Self-Report Questionnaires and Composite Clinical Disease Index for Assessing Rheumatoid Arthritis Activity: Identification of Cut-Off Points for Routine Care

    PubMed Central

    Salaffi, Fausto; Carotti, Marina; Gutierrez, Marwin; Di Carlo, Marco; De Angelis, Rossella

    2015-01-01

    Objective. To provide information on the value of Patient Acceptable Symptom State (PASS) in rheumatoid arthritis (RA) by the identification of PASS thresholds for patient-reported outcomes (PROs) composite scores. Methods. The characteristics of RA patients with affirmative and negative assignment to PASS were compared. Contributors to physician response were estimated by logistic regression models and PASS thresholds by the 75th percentile and receiver-operating characteristic (ROC) curve methods. Results. 303 RA patients completed the study. All PROs were different between the PASS (+) and PASS (−) groups (p < 0.0001). The thresholds with the 75th percentile approach were 2.0 for the RA Impact of Disease (RAID) score, 2.5 for the PRO-CLinical ARthritis Activity (PRO-CLARA) index, and 1.0 for the Recent-Onset Arthritis Disability (ROAD) questionnaire. The cut-off values for Clinical Disease Activity Index (CDAI) were in the moderate range of disease activity. Assessing the size of the logistic regression coefficients, the strongest predictors of PASS were the disease activity (p = 0.0007) and functional state level (0.006). Conclusion. PASS thresholds were relatively high and many patients in PASS had moderate disease activity states according to CDAI. Factors such as disease activity and physical function may influence a negative PASS. PMID:26167506

  6. 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

  7. Effect of intensive exercise on patients with active rheumatoid arthritis: a randomised clinical trial

    PubMed Central

    van den Ende, C H M; Breedveld, F; le Cessie, S; Dijkmans, B; de Mug, A W; Hazes, J

    2000-01-01

    OBJECTIVE—To investigate the effects of a dynamic, intensive exercise regimen on pain, disease activity, and physical functioning in active rheumatoid arthritis (RA).
METHODS—64 patients with RA with a mean age of 60 (13) years and mean disease duration of 8 (8) years, admitted to hospital because of active disease, were randomly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 (14) days. The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises. Indices of disease activity, pain, muscle strength, and functional ability were assessed at 0, 3, 6, 12, and 24 weeks by a blinded observer.
RESULTS—The medical treatment during the study was the same in both groups. Both groups improved in measures of disease activity, differences between groups were not statistically significant. The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was −1.4 (1.5) and −0.7 (1.4), respectively. Measures of physical functioning improved significantly for patients in the intensive exercise group, and differences between groups were statistically significant for measures of muscle strength.
CONCLUSION—A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity.

 PMID:10913058

  8. 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

  9. Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

    PubMed

    Mokhtar, Galila M; El-Beblawy, Nagham M S; Adly, Amira A; Elbarbary, Nancy S; Kamal, Tarek M; Hasan, Esraa M

    2016-04-01

    To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP. PMID:27007229

  10. Patient Activation: Public Libraries and Health Literacy

    ERIC Educational Resources Information Center

    Malachowski, Margot

    2011-01-01

    Patient activation is a new term for a perennial problem. People know what they need to do for their health: exercise, eat right, and get enough rest--but how are they motivated to actually do these things? This is what patient activation is. From this author's vantage point as a medical librarian, public libraries are well-placed to be part of…

  11. Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy.

    PubMed Central

    Hahn, G; Stuhlmüller, B; Hain, N; Kalden, J R; Pfizenmaier, K; Burmester, G R

    1993-01-01

    One of the hallmarks in rheumatoid arthritis (RA) is the intense activation of the monocyte-macrophage system. In the present investigation, the modulation of blood monocyte activation was studied with regard to the secretion of cytokines and inflammatory mediators, and to the expression of cytokine receptors. Patients with severe active RA underwent repeated leukapheresis procedures that removed all circulating monocytes. Highly enriched monocyte preparations from the first and third leukapheresis were studied. There were striking differences between the two monocyte populations. Cells obtained from the first leukapheresis constitutively released large amounts of prostaglandin E2 (PGE2), neopterin, interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In particular, IL-1 beta and neopterin production were further enhanced by stimulation with either interferon-gamma (IFN-gamma) or TNF-alpha without a synergistic effect. In contrast, cells derived from the third leukapheresis procedure showed a close to normal activation status with only low levels of cytokine and mediator production as well as a reduced response to cytokine stimulation. The number of the receptors for IFN-gamma and TNF-alpha was not changed between first and third leukapheresis. However, TNF-binding capacity was only detectable upon acid treatment of freshly isolated monocytes. A further upregulation was noted upon 24 h in vitro culture, suggesting occupation of membrane receptors and receptor down-regulation by endogenously produced TNF-alpha. Northern blot analysis of cytokine gene expression was in good correlation with the amount of mediators determined on the protein level. These data indicate that cells of the monocyte-macrophage system are already highly activated in the peripheral blood in RA patients with active disease. These cells can be efficiently removed by repeated leukapheresis and are replenished by monocytes that have, with respect to cytokine and mediator

  12. Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Meyer, Pieter W. A.; Hodkinson, Bridget; Ally, Mahmood; Musenge, Eustasius; Wadee, Ahmed A.; Fickl, Heidi; Tikly, Mohammed; Anderson, Ronald

    2010-01-01

    Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA. PMID:21437211

  13. Patient education, disease activity and physical function: can we be more targeted? A cross sectional study among people with rheumatoid arthritis, psoriatic arthritis and hand osteoarthritis

    PubMed Central

    2013-01-01

    Introduction In order to target educational needs of patients more effectively, an Austrian-German educational needs assessment tool (OENAT) was developed, the educational needs of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and hand osteoarthritis (HOA) were described and the relationships between educational needs, gender, disease activity and function were explored. Methods The English ENAT was adapted into Austrian-German using Beaton's cross-cultural adaptation process. Internal construct validity was assessed by Rasch analysis. Educational needs across diagnostic groups and subgroups of patients were summarized descriptively and their relationship with disease activity and physical functioning explored. Results The sample comprised 130 RA, 125 PsA and 48 HOA patients. Their mean ages ± SD were 56 ± 14, 51 ± 11 and 64 ± 7 years for RA, PsA and HOA; disease duration was 11 ± 9, 11 ± 11 and 14 ± 9 years, respectively. More than 70% in each patient group expressed interest in receiving education about their disease. The educational needs differed significantly between women and men in all 3 groups. In RA and PsA, female patients expressed significantly higher educational needs than men in 'movements’ and 'feelings’ domains (p=0.04 and p=0.03 for RA and p<0.01 and p=0.01 for PsA). Female patients in the HOA group had significantly higher scores on all domains except for the 'movements’. Older patients with PsA scored significantly higher than their younger counterparts in the 'pain’ domain (p=0.05). RA patients with disease duration >5 years), expressed higher educational needs in 'movements’ (p<0.01). Educational background had effects in the PsA group only, patients with basic education had greater scores than those with higher education on 'movements’ and 'arthritis process’ (p=0.01). In the RA group, DAS28 correlated significantly with 'movements’ (r=0.24, p=0.01), 'feelings’ (r=0.22, p

  14. Uptake and degradation of soluble aggregates of IgG by monocytes of patients with rheumatoid arthritis: relation to disease activity.

    PubMed Central

    Heurkens, A H; Westedt, M L; Breedveld, F C; Jonges, E; Cats, A; Stijnen, T; Daha, M R

    1991-01-01

    Monocytes from patients with rheumatoid arthritis (RA) and rheumatoid vasculitis have a diminished ability to degrade soluble complexes of aggregated IgG in the absence (mediated by Fc receptors) as well as in the presence of complement (C) (mediated by (Fc + C) receptors). To investigate whether a relation exists between the receptor mediated degradation of aggregated IgG by adherent monocytes and disease activity a longitudinal study was performed in 79 patients with RA and rheumatoid vasculitis over a period of 16 months. Adherent monocytes were incubated in vitro with 125I labelled IgG aggregates of restricted size in the absence or presence of fresh serum and the percentage of catabolised IgG aggregates was measured. Cross sectionally the degradation of aggregated IgG by monocytes, mediated by Fc and (Fc + C) receptors, correlated significantly with disease activity as scored by the Ritchie articular index, the presence of extra-articular features, and circulating immune complexes. A high number of Fc receptors on monocytes correlated with diminished degradation, whereas high numbers of complement receptors 1 and 3 correlated with enhanced degradation of aggregated IgG mediated by both Fc and (Fc + C) receptors. The degradation of aggregated IgG by monocytes did not correlate with disease activity in individual patients followed up longitudinally. When patient groups were formed according to the results of longitudinal studies, however, degradation of aggregated IgG mediated by Fc and (Fc + C) receptors was significantly decreased in patients with rheumatoid vasculitis and in patients with active RA in comparison with patients with inactive RA and healthy controls. Patients with active RA and rheumatoid vasculitis also expressed significantly more Fc receptors and less complement receptors on the monocytes than patients with inactive RA. Drug treatment did not correlate with receptor expression or the degradation of aggregated IgG by monocytes either in cross

  15. HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA.

    PubMed Central

    Singal, D P; Green, D; Reid, B; Gladman, D D; Buchanan, W W

    1992-01-01

    The distribution of HLA-D region antigens was studied in three groups (I, IIa, and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to gold and developed gold induced toxic reactions, including thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by serological and molecular (Southern blot analysis and oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed gold induced toxic reactions (group IIb). These data suggest that the HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA. Images PMID:1371662

  16. Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set

    PubMed Central

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H; Lin, Daming; Alten, Rieke; Christensen, Robin; Furst, Daniel E; Hewlett, Sarah; Leong, Amye; March, Lyn; Woodworth, Thasia; Boire, Gilles; Haraoui, Boulos; Hitchon, Carol; Jamal, Shahin; Keystone, Edward C; Pope, Janet; Tin, Diane; Thorne, J Carter

    2016-01-01

    Objective To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. Methods Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). Results The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16–32% were flaring at the second visit. Agreement of flare status was low–strong (κ's 0.17–0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49–0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29–0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1–3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. Conclusions Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares. PMID

  17. Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results Circulating IC in the serum of RA patients and healthy controls contain fibrinogenβ and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogenγ and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogenβ were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions Citrullinated fibrinogenβ and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA- RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin

  18. 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

  19. Adrenal function in patients with active tuberculosis.

    PubMed Central

    Barnes, D J; Naraqi, S; Temu, P; Turtle, J R

    1989-01-01

    Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function. PMID:2763243

  20. Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1β in Patients With Type 1 Diabetes

    PubMed Central

    Purohit, Sharad; Sharma, Ashok; Hopkins, Diane; Steed, Leigh; Bode, Bruce; Anderson, Stephen W.; Reed, John Chip; Steed, R. Dennis; Yang, Tao

    2015-01-01

    Context: Previous studies have attempted to elucidate the potential role of various cytokines and chemokines in human type 1 diabetes (T1D); however, the precise role of these serum proteins in T1D is still controversial and undetermined primarily due to the small sample sizes of the previous studies. We profiled a panel of serum cytokines and chemokines using a large-scale, two-stage study design for the discovery and validation of the serum proteins associated with T1D. Participants: The participants were patients with T1D and islet autoantibody–negative control subjects from the Phenome and Genome of Diabetes Autoimmunity study. Main Outcome Measures: Thirteen cytokines and chemokines were measured in serum of 4424 subjects using multiplex immunoassays. Results: Using 1378 samples in Stage 1, we found that four of the 13 proteins are significantly lower in patients with T1D than controls (IL8: odds ratio [OR] = 0.40; P = 5.7 × 10−19; IL-1Ra: OR = 0.42; P = 1.1 × 10−13; MCP-1: OR = 0.60; P = 6.7 × 10−9; and MIP-1β: OR = 0.63; P = 4.2 × 10−7). Our confirmation data with 3046 samples in Stage 2 further confirmed the significant negative associations of these four proteins with T1D (IL8: OR = 0.43; P = 8.9 × 10−32; IL-1Ra: OR = 0.56, P = 3.7 × 10−27; MCP-1: OR = 0.61, P = 4.3 × 10−17; and MIP-1β: OR = 0.69, P = 2.4 × 10−13). Quartile analyses also suggested that significantly more T1D cases have protein levels in the bottom quartile than in the top quartile for all four proteins: IL8 (OR = 0.09), IL-1Ra (OR = 0.18), MCP-1 (OR = 0.38), and MIP-1β (OR = 0.44). Furthermore, the negative associations between T1D and serum levels of all four proteins are stronger in genetically high-risk groups compared with the moderate and low-risk groups. Conclusions: IL8, IL-1Ra, MCP-1, and MIP-1β are significantly lower in patients with T1D than controls. PMID:26158606

  1. Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid arthritis treated with combined conventional disease-modifying antirheumatic drugs or biologics.

    PubMed

    Osiri, Manathip; Wongpiyabovorn, Jongkonnee; Sattayasomboon, Youwanuch; Thammacharoenrach, Niramol

    2016-07-01

    The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-γ, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-α in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA. PMID:27188857

  2. [Pseudocholinesterase activity in type 1 bipolar patients].

    PubMed

    Ezzaher, Asma; Haj Mouhamed, Dhouha; Mechri, Anwar; Neffati, Fadoua; Douki, Wahiba; Gaha, Lotfi; Najjar, Mohamed Fadhel

    2012-01-01

    This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 ± 12.2 and 36.4 ± 15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plus™. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk. PMID:22294139

  3. Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy

    PubMed Central

    Mottonen, T; Paimela, L; Leirisalo-Repo, M; Kautiainen, H; Ilonen, J; Hannonen, P

    1998-01-01

    OBJECTIVES—To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis (RA) treated actively with slow acting antirheumatic drugs (SAARDs).
METHODS—A total of 142 consecutive patients with early RA (median disease duration of 7 months) were treated according to the "sawtooth" strategy and prospectively followed up for an average of 6.2 years. Several clinical parameters at start as well as genetic markers were related to the functional outcome (ARA Functional class and HAQ disability score) and radiographic joint damage (Larsen's score) at the latest visit.
RESULTS—In logistic regression analysis only Mallya score (including morning stiffness, pain scale, grip strength, Ritchie's articular index, haemoglobin, and erythrocyte sedimentation rate) at baseline, and Mallya score and rheumatoid factor (RF) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients. Furthermore, at the latest visit HAQ score was related to radiographic score. At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors (44 v 49, p=0.03 and 41 v 53, p=0.04, respectively). However, these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients.
CONCLUSION—High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA. However, from the clinical point of view, the disease outcome of an individual patient with early RA, cannot be predicted accurately enough by present means.

 Keywords: rheumatoid arthritis; prognosis; outcome; prediction PMID:9849312

  4. [Hypercoagulable state is associated with NF-kappa B activation and increased inflammatory factors in patients with rheumatoid arthritis].

    PubMed

    Zhang, Pingheng; Liu, Jian; Tan, Bing; Zhu, Fubing; Fang, Li

    2016-03-01

    Objective To investigate the mechanism of hypercoagulable state based on nuclear factor κB (NF-κB) pathway in patients with rheumatoid arthritis (RA). Methods Thirty-five RA patients were enrolled as well as 20 healthy volunteers as a control group. Interleukin-10 (IL-10), IL-6, IL-4, IL-17, NF-κB activator 1 (Act1), p50, p65, IκBα, platelet activating factor (PAF), PAF-acetylhydrolase (PAF-AH) and anti-cyclic citrullinated peptide (CCP) were detected using ELISA. The number of platelet (PLT) was detected using Sysmex XT-2000i automated hematology analyzer. The levels of D-dimer (D-D), fibrinogen (FBG), thrombin time (TT), prothrombin time (PT), and partial thromboplastin time (APTT) were detected using Sysmex CA-1500 automatic coagulation analyzer. Erythrocyte sedimentation rate (ESR) was detected using Westergren method. C-reactive protein and rheumatoid factor (RF) were detected using Hitachi 7060 automatic biochemical analyzer. Meanwhile, the mRNA expressions of Act1, p65, p50, IκBα and IκB kinase α (IKKα) were detected using semi-quantitative reverse transcription PCR. The expressions of p65, p50 and IκBα proteins were examined using Western blotting. The correlations of the above indexes were analyzed by Spearman correlation test. Results Compared with the normal group, the levels of DD, FBG, PLT significantly increased in the peripheral blood of RA patients, TT decreased, while APTT and PT were not significantly changed. IL-4, IL-10 and PAF-AH were significantly reduced in the sera of RA patients, while IL-6, IL-17, Act1, p50, p65, IκBα, IKKα and PAF were significantly elevated. Spearman correlation analysis showed that coagulant and fibrinolytic indexes were significantly correlated with cytokines, NF-κB, activity indexes and clinical symptoms and signs. Conclusion The hypercoagulable state is common in the peripheral blood of RA patients, and it is closely related to inflammatory factors, activity indexes and abnormal activation of NF

  5. Lithium chloride antileukemic activity in acute promyelocytic leukemia is GSK-3 and MEK/ERK dependent.

    PubMed

    Zassadowski, F; Pokorna, K; Ferre, N; Guidez, F; Llopis, L; Chourbagi, O; Chopin, M; Poupon, J; Fenaux, P; Ann Padua, R; Pla, M; Chomienne, C; Cassinat, B

    2015-12-01

    We recently identified that the MEK/ERK1/2 pathway synergized with retinoic acid (RA) to restore both transcriptional activity and RA-induced differentiation in RA-resistant acute promyelocytic leukemia (APL) cells. To target the MEK/ERK pathway, we identified glycogen synthase kinase-3β (GSK-3β) inhibitors including lithium chloride (LiCl) as activators of this pathway in APL cells. Using NB4 (RA-sensitive) and UF-1 (RA-resistant) APL cell lines, we observed that LiCl as well as synthetic GSK-3β inhibitors decreased proliferation, induced apoptosis and restored, in RA-resistant cells, the expression of RA target genes and the RA-induced differentiation. Inhibition of the MEK/ERK1/2 pathway abolished these effects. These results were corroborated in primary APL patient cells and translated in vivo using an APL preclinical mouse model in which LiCl given alone was as efficient as RA in increasing survival of leukemic mice compared with untreated mice. When LiCl was combined with RA, we observed a significant survival advantage compared with mice treated by RA alone. In this work, we demonstrate that LiCl, a well-tolerated agent in humans, has antileukemic activity in APL and that it has the potential to restore RA-induced transcriptional activation and differentiation in RA-resistant APL cells in an MEK/ERK-dependent manner. PMID:26108692

  6. Physical activity in patients with anorexia nervosa.

    PubMed

    Achamrah, Najate; Coëffier, Moïse; Déchelotte, Pierre

    2016-05-01

    Anorexia nervosa (AN) is often associated with physical hyperactivity. Recent studies have established links between anorexia and hyperactivity, suggesting the existence of commonalities in neural pathways. How physical activity should be managed during the clinical care of patients with anorexia remains controversial. This review first focuses on the implication of hyperactivity in the pathophysiology of AN. Hyperactivity during refeeding of patients with AN has been associated with increased energy needs to achieve weight gain, poorer clinical outcome, longer hospitalization, and increased psychiatric comorbidity. This typically leads to the prescription of bed rest. However, current knowledge suggests that preserving some kind of physical activity during refeeding of patients with AN should be safe and beneficial for the restoration of body composition, the preservation of bone mineral density, and the management of mood and anxiety. In the absence of standardized guidelines, it is suggested here that physical activity during refeeding of patients with AN should be personalized according to the physical and mental status of each patient. More research is needed to assess whether programmed physical activity may be a beneficial part of the treatment of AN. PMID:27052638

  7. Prolidase activity in chronic plaque psoriasis patients

    PubMed Central

    Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver

    2015-01-01

    Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776

  8. Antibodies against a novel nucleolar and cytoplasmic antigen (p105-p42) present in the sera of patients with a subset of rheumatoid arthritis (RA) with signs of scleroderma

    PubMed Central

    Labrador, M; Algueró, A; Díaz, C; Geli, C; Pérez, E; García-Valero, J; Rodriguez-Sanchez, J L; Gelpí, C

    1998-01-01

    We identified three patients (two of them relatives) with RA and signs of scleroderma whose sera contained a high titre of IgG class antibodies against the nucleoli and the nucleoplasm of cells of different mammalian origins. Sera from these patients uniformly immunoprecipitated four polypeptides, from a 35S-methionine-labelled HeLa cell extract, whose mol. wts were 120, 105, 95 and 42 kD. Of these, the 95-kD protein was highly phosphorylated. By immunoblotting, these sera reacted with 105-, 95- and 42-kD proteins and affinity-purified antibodies from these, demonstrating that 105- and 95-kD proteins shared cross-reactive epitopes. Moreover, affinity-purified antibodies from each of these proteins immunoprecipitated the whole complex. Localization studies using immunoelectron microscopy and in vivo actinomycin-D-treated cells demonstrated that the 105-, 95- and 42-kD proteins were present in the granular component of the nucleolus and the nucleoplasm. In addition, the 105- and 95-kD were present in free polyribosomes as well as ribosomes attached to endoplasmic reticulum. Pulse/chase experiments strongly suggested that the complex was accomplished shortly after a 10-min pulse. It was preferentially present in the nucleus after a 2 h chase and in both nucleus and cytoplasm after a 5 h chase. We conclude that a protein complex with a main nucleolar distribution is a new autoantigen (p105-p42) recognized by autoantibodies present in the serum of a subgroup of patients with RA and scleroderma signs. These antibodies could be useful as diagnostic markers and as tools for further studies involving the biology of the nucleolus. PMID:9822291

  9. Remission in rheumatoid arthritis: benefit over low disease activity in patient-reported outcomes and costs

    PubMed Central

    2014-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes a considerable burden for the patient and society. It is not clear yet whether aiming for remission (REM) is worthwhile, especially when compared with low disease activity (LDA). Methods In 356 consecutive RA patients, we obtained data on physical function (health assessment questionnaire (HAQ)), health-related quality of life (HRQoL: Short Form 36 (SF36), Short Form 6 dimensions (SF-6D), Euro QoL 5D (EQ-5D)), work productivity (work productivity and activity impairment questionnaire (WPAI)), as well as estimation of direct and indirect costs. Cross-sectionally, data were compared in patients within different levels of disease activity according to the simplified disease activity index (SDAI; remission (REM ≤3.3); n = 87; low disease activity (LDA: 3.3 < SDAI ≤11); n = 103; moderate to high disease activity (MDA/HDA) >11 n = 119) by using analyses of variance (ANOVA). Longitudinal investigations assessed patients who changed from LDA to REM and vice versa. Results We found differences in patients achieving REM compared with LDA for HAQ (0.39 ± 0.58 versus 0.72 ± 68), WPAI (percentage impairment while working 11.8% ± 18.7% versus 26.8% ± 23.9%; percentage of overall activity impairment, 10.8% ± 14.1% versus 29.0% ± 23.6%)), EQ-5D (0.89 ± 0.12 versus 0.78 ± 0.6) and SF-36 (physical component score (PCS): 46.0 ± 8.6 versus 38.3 ± 10.5; mental component score (MCS): 49.9 ± 11.1 versus 47.9 ± 12.3) (P < 0.01 for all, except for SF36 MCS). Regarding costs, we found significant differences of direct and indirect costs (P < 0.05) within different levels of disease activity, with higher costs in patients with higher states of disease activity. Longitudinal evaluations confirmed the main analyses. Conclusion Patients with REM show better function, HRQoL, and productivity, even when compared with another

  10. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

    PubMed Central

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Villa, Antonio R; Cabiedes, Javier; Rull-Gabayet, Marina

    2009-01-01

    Introduction Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. Methods Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. Results The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age

  11. 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

  12. [Peculiarities of verbal activity in migraine patients].

    PubMed

    Latysheva, N V; Iakovlev, O N; Filatova, E G

    2003-01-01

    We applied associative verbal experiment to analyze verbal activity of migraineurs. A test group consisted of 49 patients with migraine, a control one--of 20 healthy people. Reliable decrease of free associations number, verbs and plants, semantic index and changes of non-productive association index and coefficient were observed. Average depression level, higher anxiety and negative correlations with indexes calculated were found. Verbal activity of migraineurs, their ability to concentrate and to control adequateness of task fulfillment were decreased. That was caused by pain, depression, anxiety and neurotization. Verbal activity is influenced by individual emotional features (calculated indexes do not correlate with the visual analogue scale). PMID:12938648

  13. 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

  14. The effects of isometric exercise types on pain and muscle activity in patients with low back pain.

    PubMed

    Rhyu, Hyun-Seung; Park, Hun-Kyung; Park, Jung-Sub; Park, Hye-Sang

    2015-08-01

    The purpose of the present study is to evaluate the effects of isometric exercise types on low back pain (LBP) patients. Isometric exercise types were mat exercise and I-Zer exercise. Subjects were divided into 3 groups: LBP control group, LBP mat exercise group, and LBP I-Zer exercise group in 23-25 aged men. Visual analogue scale (VAS) and electromyography (EMG) were used to evaluate the degree of pain and the muscle activity in LBP patients. Root mean square (RMS), median frequency (MDF), and mean frequency (MNF) were checked by EMG power spectrum analysis on longissimus thoracic (LT), iliocostalis lumborum (IL), mulitifidus (M), and rectus abdominis (RA). LBP mat exercise program and LBP I-Zer exercise program were conducted 5 sets once time, 3 times per week during 6 weeks. The two-way ANOVA with repeated measure was used to check the pain degree and muscle activity. The present results showed that muscle activity in the LBP I-Zer exercise group was increased compared to the LBP mat exercise group and LBP control group (P<0.05). LBP I-Zer exercise group and LBP mat exercise group showed increased mean frequency in LT, IL, M, and RA muscles than the LBP control group. Therefore, LBP patients performed isometric exercise may have positive effect to reduce pain degree and to increase muscle activity. Especially, LBP I-Zer exercise type showed more effectiveness in reducing pain degree and enhancing muscle activity. PMID:26331136

  15. The effects of isometric exercise types on pain and muscle activity in patients with low back pain

    PubMed Central

    Rhyu, Hyun-Seung; Park, Hun-Kyung; Park, Jung-Sub; Park, Hye-Sang

    2015-01-01

    The purpose of the present study is to evaluate the effects of isometric exercise types on low back pain (LBP) patients. Isometric exercise types were mat exercise and I-Zer exercise. Subjects were divided into 3 groups: LBP control group, LBP mat exercise group, and LBP I-Zer exercise group in 23–25 aged men. Visual analogue scale (VAS) and electromyography (EMG) were used to evaluate the degree of pain and the muscle activity in LBP patients. Root mean square (RMS), median frequency (MDF), and mean frequency (MNF) were checked by EMG power spectrum analysis on longissimus thoracic (LT), iliocostalis lumborum (IL), mulitifidus (M), and rectus abdominis (RA). LBP mat exercise program and LBP I-Zer exercise program were conducted 5 sets once time, 3 times per week during 6 weeks. The two-way ANOVA with repeated measure was used to check the pain degree and muscle activity. The present results showed that muscle activity in the LBP I-Zer exercise group was increased compared to the LBP mat exercise group and LBP control group (P<0.05). LBP I-Zer exercise group and LBP mat exercise group showed increased mean frequency in LT, IL, M, and RA muscles than the LBP control group. Therefore, LBP patients performed isometric exercise may have positive effect to reduce pain degree and to increase muscle activity. Especially, LBP I-Zer exercise type showed more effectiveness in reducing pain degree and enhancing muscle activity. PMID:26331136

  16. Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential biomarkers for disease activity and the role of antioxidants.

    PubMed

    Khojah, Hani M; Ahmed, Sameh; Abdel-Rahman, Mahran S; Hamza, Al-Badr

    2016-08-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have distinct contribution to the destructive, proliferative synovitis of rheumatoid arthritis (RA) and play a prominent role in cell-signaling events. However, few studies had clarified the role of individual ROS and RNS in the etiopathogenesis of RA. To date, most of the studies were concerned with the measurement of the total oxidative and nitrative stress levels in RA. The aim of this study was to monitor the levels of individual ROS and RNS to emphasize the role that each plays in the pathogenesis of RA and their usefulness as possible biomarkers for the disease activity. In addition, the effect of an antioxidant (ascorbic acid), added to the treatment regimen, on the levels of ROS, RNS and disease activity has been evaluated. Forty-two Saudi RA patients and 40 healthy controls of both genders were included in this study. Serum levels of six different ROS and three different RNS were measured using specific fluorescent probes. The ROS included the hydroxyl radical ((•)OH), the superoxide anion (O2(•-)), hydrogen peroxide (H2O2), the singlet oxygen ((1)O2), the hypochlorite radical (OHCl(•)), and the peroxyl radical (ROO(•)). The RNS included nitric oxide (NO(•)), nitrogen dioxide (ONO-) and peroxynitrite (ONOO-). The main clinical and biochemical markers for disease activity were assessed and correlated with ROS and RNS levels. The clinical markers included the 28 swollen joint count (SJC-28), the 28-tender joint count (TJC-28), morning stiffness and symmetric arthritis, in addition to the disease activity score assessing 28 joints with erythrocyte sedimentation rate (DAS28-ESR). The biochemical markers included undercarboxylated osteocalcin (ucOC), matrix metalloproteinase (MMP-3), ESR, C-reactive protein (CRP), rheumatoid factor (RF) and anticyclic citrullinated polypeptide (Anti-CCP). Ascorbic acid (1mg/day) was added as an antioxidant to the regular treatment regimen of RA patients

  17. Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat-to-target strategy.

    PubMed

    Siemons, Liseth; Ten Klooster, Peter M; Vonkeman, Harald E; Glas, Cees A W; Van de Laar, Mart a F J

    2014-04-01

    Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, important individual variations exist in the course towards remission. Growth mixture modeling (GMM) provides more insight into this heterogeneity by identifying subgroups of patients with similar response patterns. This study aimed to identify distinct trajectories of disease activity in early RA patients following a T2T strategy, during their first year. Methods: Data on various clinical and patient-reported measures were collected from the DREAM remission induction cohort. GMM was applied to examine the impact of T2T on subgroups characterized by different types of growth trajectories, as measured with the Disease Activity Score for 28 joints. Results: Three distinct trajectories of disease activity were found. The normative trajectory contained most patients (82.6%), showing a quickly decreasing disease activity, stabilizing at remission after 9 months. This group performed best on clinical and patient-reported measures over time and were more likely to be men. A smaller group (14.1%) also approached remission, but demonstrated a slower response to treatment. Finally, a minority (3.3%) showed no improvement after 1 year, despite an initial quick decrease in disease activity during the first months of treatment. Conclusion: Disease activity in early RA patients during the first year of a T2T strategy does not follow a linear pattern, nor is a single developmental trajectory applicable to all patients. Future studies should attempt to identify more specific risk factors for poor outcome to enable early identification of patients in need of alternative therapeutic approaches. PMID:24106173

  18. Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4(+)CD25(high)CD45RA(+) regulatory T cell production and modulating cytokine secretion.

    PubMed

    Yang, Hongna; Sun, Jinhua; Li, Yan; Duan, Wei-Ming; Bi, Jianzhong; Qu, Tingyu

    2016-04-01

    Bone marrow-derived mesenchymal stem cells (MSCs) are promising candidate cells for therapeutic application in autoimmune diseases due to their immunomodulatory properties. Unused human umbilical cords (UC) offer an abundant and noninvasive source of MSCs without ethical issues and are emerging as a valuable alternative to bone marrow tissue for producing MSCs. We thus investigated the immunomodulation effect of umbilical cord-derived MSCs (UC-MSCs) on human peripheral blood mononuclear cells (PBMCs), T cells in particular, in a co-culture system. We found that UC-MSCs efficiently suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated PBMCs (p<0.01). Kinetic analysis revealed that UC-MSCs primarily inhibited the division of generation 3 (G3) and 4 (G4) of PBMCs. In addition, UC-MSCs augmented the expression of CD127(+) and CD45RA(+) but reduced the expression of CD25(+) in PBMCs stimulated by PHA (p<0.05). Furthermore, UC-MSCs inhibited PHA-resulted increase in the frequency of CD4(+)CD25(+)CD127(low/-) Tregs significantly (p<0.01) but augmented PHA-resulted increase in the frequency of CD4(+)CD25(high)CD45RA(+) Tregs to about three times in PBMCs. The levels of anti-inflammatory cytokines, PEG2, TGF-β, and IL-10 were greatly up-regulated, accompanied by a significant down-regulation of pro-inflammatory IFN-γ in the co-culture (p<0.01). Our results showed that UC-MSCs are able to suppress mitogen-induced PBMC activation and proliferation in vitro by altering T lymphocyte phenotypes, increasing the frequency of CD4(+)CD25(high)CD45RA(+) Tregs, and modulating the associated cytokine production. Further studies are warranted to investigate the therapeutic potential of UC-MSCs in immunologically-diseased conditions. PMID:26774852

  19. Ra-224 and Ra-226: A New Method for Measuring Groundwater Seepage in Lake Michigan

    NASA Astrophysics Data System (ADS)

    Stevens, K. R.; Buyan, A. C.; Waples, J. T.

    2008-12-01

    Radium isotopes have been used to estimate groundwater discharge (GWD) in coastal marine waters for decades, but this technique has never before been used in the Laurentian Great Lakes. In this study, we used a RAD7 radon-in-air monitor to measure naturally-occurring radium isotopes Ra-224 (half-life= 3.64 d) and Ra-226 (half-life = 1600 a) in groundwater and three shallow water sites along Lake Michigan's Wisconsin coastline. Radium-224 activities in groundwater ranged from 1153 dpm m-3 in a deep aquifer (New Berlin well no.7) to 31 dpm m-3 in a shallow aquifer (Pryor well). Nearshore Lake Michigan measurements of Ra-224 were lowest at Red Arrow Beach (0.2 dpm m-3), higher in the Milwaukee harbor (GLWI slip, 1.1 dpm m-3) and highest at Harrington Beach (4.1 dpm m-3) and correspond well with groundwater seepage estimates made by Cherkauer et al. (1990) using alternate methods (i.e., where higher radium activity is indicative of higher GWD). These Ra-224 measurements are the first ever made in Lake Michigan (and presumably any of the Great Lakes) and we conclude that, by sampling offshore radium activity gradients, this RAD7 technique is a viable method for directly measuring GWD in Lake Michigan and other freshwater systems.

  20. RAndomized Comparison of raDIal vs. femorAL Access for Routine Catheterization of Heart Transplant Patients (RADIAL-heart transplant study).

    PubMed

    Scalone, G; Brugaletta, S; Martín-Yuste, V; Seixo, F; Cotes, C; Gómez-Monterrosas, O; Alvarez-Contreras, L; Campreciós, M; Mirabet, S; Brossa, V; Sabaté, M

    2014-12-01

    Although a transradial approach (TRA) is considered feasible in many clinical situations, no data are available in patients undergoing orthotopic heart transplantation (OHT). Our goal was to randomly compare TRA versus a transfemoral approach (TFA) in this clinical setting. This single-center, prospective, randomized trial was conducted from January to November 2006, and all OHT patients scheduled for a control coronary angiography were randomized to receive TRA or TFA. The primary endpoint was the amount of contrast used during the procedure. The participating interventional cardiologists were intermediate-volume radial operators, and this was their initial experience of TRA in OHT patients. The analysis was performed according to the intention-to-treat principle. Overall, 49 patients (mean age, 55 ± 13 years; 74% male) were included in the trial: 26 patients were assigned to TRA, and 23 were assigned to TFA. A higher amount of contrast (147 mL [range, 113-175 mL] vs 105 mL [range, 86-127 mL]; P = .009), a longer fluoroscopy time (9.2 minutes [range, 6-12 minutes] vs 3.5 minutes [range, 3-5 minutes]; P < .001), a trend toward increased number of catheters used for left ostium cannulation, and a higher crossover rate (19% vs 0%; P = .03) were associated with TRA compared with TFA. Furthermore, patients treated with TRA exhibit a shorter hospital stay (6 [range 4-8]) compared with the other group (26 [range 24-28]) (P < .001). There were no significant differences between the 2 groups regarding total procedural time, and no vascular complications were reported in either group. For these operators with their first experience of TRA in OHT patients, TFA seemed to be more efficient. PMID:25498035

  1. 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.

  2. Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study

    PubMed Central

    Thomsen, Tanja; Beyer, Nina; Aadahl, Mette; Hetland, Merete L.; Løppenthin, Katrine; Midtgaard, Julie; Esbensen, Bente A.

    2015-01-01

    Background Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. Methods Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. Results SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. Conclusions SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients’ motivation towards sustainable change in SB and activity patterns. PMID:26462971

  3. 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 Central

    Durez, P; Nzeusseu, T; Lauwerys, B; Manicourt, D; Verschueren, P; Westhovens, R; Devogelaer, J; Houssiau, F

    2004-01-01

    Objectives: To compare the short term clinical and biological effects of intravenous (IV) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment. Methods: Patients with active RA despite MTX treatment were randomly allocated to receive a single IV infusion of MP (1 g) or three IV 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. Results: 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. Conclusion: 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. PMID:15308515

  4. Prediction of Large Joint Destruction in Patients With Rheumatoid Arthritis Using 18F-FDG PET/CT and Disease Activity Score

    PubMed Central

    Suto, Takahito; Okamura, Koichi; Yonemoto, Yukio; Okura, Chisa; Tsushima, Yoshito; Takagishi, Kenji

    2016-01-01

    Abstract The assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee, and ankle. Few studies have been reported regarding the degree of large joint destruction in RA patients. 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) visualizes the disease activity in large joints affected by RA. In this study, the associations between destruction of the large joints and the findings of FDG-PET/CT as well as laboratory parameters were investigated, and factors associated with large joint destruction after the administration of biological therapy were identified in RA patients. A total of 264 large joints in 23 RA patients (6 men and 17 women; mean age of 66.9 ± 7.9 years) were assessed in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The extent of FDG uptake in large joints (shoulder, elbow, wrist, hip, knee, and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient obtained at baseline and after 2 years were assessed according to Larsen's method. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within 2 years. Radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and 6 months, and the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) at 6, 12, and 24 months were significantly higher in the group with progressive joint destruction. The SUVmax at baseline and DAS28-ESR at 6 months were found to be factors associated with joint destruction at 2 years (P < 0.05). The FDG uptake in the joints with destruction was higher than that observed in the

  5. Adalimumab in Patients with Active Noninfectious Uveitis.

    PubMed

    Jaffe, Glenn J; Dick, Andrew D; Brézin, Antoine P; Nguyen, Quan Dong; Thorne, Jennifer E; Kestelyn, Philippe; Barisani-Asenbauer, Talin; Franco, Pablo; Heiligenhaus, Arnd; Scales, David; Chu, David S; Camez, Anne; Kwatra, Nisha V; Song, Alexandra P; Kron, Martina; Tari, Samir; Suhler, Eric B

    2016-09-01

    Background Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. Methods This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. Results The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events

  6. Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Johnson, Cheilonda; Giles, Jon T; Bathon, Joan; Lederer, David; Hoffman, Eric A; Barr, R Graham; Danoff, Sonye K

    2016-01-01

    A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10-42) and 15(IQR 5-31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007-0.05%) in RA patients and by 0.008% (95% CI, 0.003-0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population. PMID:27050433

  7. Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Johnson, Cheilonda; Giles, Jon T.; Bathon, Joan; Lederer, David; Hoffman, Eric A.; Barr, R. Graham; Danoff, Sonye K.

    2016-01-01

    A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10–42) and 15(IQR 5–31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007–0.05%) in RA patients and by 0.008% (95% CI, 0.003–0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population. PMID:27050433

  8. [Tissue grafts: an activity concerning many patients].

    PubMed

    Loty, B

    1997-11-15

    Tissue allografts mainly include corneas, bone (and cartilage, tendon, ligament, aponevrosis), skin, vessels and cardiac valves. All these grafts have been widely used for many years and were the subject of a large number of experimental and clinical studies. The different steps allowing the obtention of different tissue allografts have in fact a common organization through tissue procurement and banking activities. Tissue banks have a central situation ensuring security, safety, traceability and distribution of tissues. Appropriate organization of the banks, and respect of high level standards are thus mandatory. Tissue transplantation activity in France has been studied through national surveys: they concern more than 600 hospitals and clinics, and grafts procured in France (excluding imported allografts) are around 15,000 a year. Precise regulation implied by the bioethical law published in 1994 and homogeneous organization of the activity allow the use of stringent and regularly updated standards, allowing the distribution to the patients of safe grafts procured in ethical conditions. The actual shortage of tissue allografts in France implies increasing procurement through a better organization of retrieval in hospitals and clinics and donation promotion. PMID:9501596

  9. Production of Ra225 precursor for Ac225/Bi213 generators. Final CRADA Report.

    SciTech Connect

    Ehst, D. A.; Nuclear Engineering Division

    2009-10-02

    Russian subcontractors shipped two small deliveries of Ra225 to PNNL for evaluation. The activity was close to the requisite amount in the subcontract. The first labeled properly; the second did not. This showed that the Russians could supply Ra225 to the US; however they proved unable to meet future demands for larger amounts of activity. The US DOE attempts to get Ra225 from Russian should be terminated; the Russians, under Rosatom, are not interested in this business.

  10. Determination of 226Ra in urine samples by alpha spectrometry.

    PubMed

    Kehagia, K; Potiriadis, C; Bratakos, S; Koukouliou, V; Drikos, G

    2007-01-01

    A radiation protection system to assess the internal contamination of workers during decontamination activities in an abounded fertilizer industry in the region of Attika, Greece, has been implemented. This system concerns, among other radionuclides, 226Ra. Because of the low 226Ra activities in urine, alpha spectrometry was used as the determination method after radiochemical separation. Radium was co precipitated with lead sulphate and purified using anion and cation exchange techniques. The source for the alpha spectrometric measurement was prepared by the electrodeposition of radium, from an aqueous/ethanol solution, onto stainless steel. The tracer used was 229Th. The chemical yield and the activity concentration were calculated via its daughter radionuclide 217At. Using the time-evolution formulas to calculate the 217At growth from its parent radionuclide 225Ra, a computer software was developed. This software was incorporated in a database, which automatically calculates and stores the results. PMID:17827131

  11. IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma.

    PubMed

    Willis, Cynthia R; Siegel, Lori; Leith, Anh; Mohn, Deanna; Escobar, Sabine; Wannberg, Sharon; Misura, Kira; Rickel, Erika; Rottman, James B; Comeau, Michael R; Sullivan, John K; Metz, Daniela P; Tocker, Joel; Budelsky, Alison L

    2015-12-01

    Asthma is a heterogeneous disease characterized by airway inflammation and hyperreactivity. IL-17 receptor A (IL-17RA) is a shared receptor subunit required for activity of IL-17 family cytokines, including IL-17A and IL-25. IL-17A and IL-25 induce different proinflammatory responses, and concentrations are elevated in subjects with asthma. However, the individual contributions of IL-17A and IL-25 to disease pathogenesis are unclear. We explored proinflammatory activities of the IL-17 pathway in models of pulmonary inflammation and assessed its effects on contractility of human bronchial airway smooth muscle. In two mouse models, IL-17RA, IL-17RB, or IL-25 blockade reduced airway inflammation and airway hyperreactivity. Individually, IL-17A and IL-25 enhanced contractility of human bronchial smooth muscle induced by methacholine or carbachol. IL-17A had more pronounced effects on methacholine-induced contractility in bronchial rings from donors with asthma compared with donors without asthma. Blocking the IL-17 pathway via IL-17RA may be a useful therapy for some patients with asthma by reducing pulmonary inflammation and airway hyperreactivity. PMID:25919006

  12. High IL-23 level is a marker of disease activity in rheumatoid arthritis.

    PubMed

    Abu Al Fadl, Esam M; Fattouh, Mona; Allam, Ahmed A

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune systemic disorder characterized by inflammatory responses mainly affecting the synovial joints. Interleukin-23 (IL-23) is a heterodimeric pro-inflammatory cytokine secreted by activated dendritic cells and activated macrophages. IL-23 is the key cytokine controlling inflammation in peripheral tissues leading to the development of autoimmune diseases. The objective of our study was to determine the relationship between the IL-23 level and disease activity in RA patients. Sixty RA patients were included in the study with mean age of 40 years; they included 44 (73.3 %) females and 16 males (26.7 %). The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), serum levels of C-reactive protein (CRP), Anti-citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and TNF-alpha and the degree of bony erosions based on X-rays. Patients were subdivided into active disease group (n = 30) with DAS28 score higher than 5.1 (Group I); and remission group (n = 30) with DAS28 score less than 2.6 (Group II). Thirty healthy individuals in the same age group of RA patients including 22 (73.3%) females and 8 males (26.7%) were randomly selected as the control group (Group III). The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA) and the correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Serum levels of IL-23 were significantly higher in RA patients during active stage of the disease in comparison to the patients in remission and the control group. There was a significant positive correlation between serum IL-23 levels in RA patients and individual disease activity parameters. It is concluded that elevated serum IL-23 level may be a useful marker to detect active RA and disease progression in patients with RA. PMID:24617049

  13. Exploring Contextual Factors and Patient Activation: Evidence from a Nationally Representative Sample of Patients with Depression

    ERIC Educational Resources Information Center

    Chen, Jie; Mortensen, Karoline; Bloodworth, Robin

    2014-01-01

    Patient activation has been considered as a "blockbuster drug of the century." Patients with mental disorders are less activated compared to patients with other chronic diseases. Low activation due to mental disorders can affect the efficiency of treatment of other comorbidities. Contextual factors are significantly associated with…

  14. Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of Rheumatoid Arthritis

    PubMed Central

    Šenolt, Ladislav; Šumová, Barbora; Jandová, Romana; Hulejová, Hana; Mann, Heřman; Pavelka, Karel; Vencovský, Jiří; Filková, Mária

    2015-01-01

    Objectives To study the association of systemic and local interleukin-35 (IL-35) levels in rheumatoid arthritis. Methods 37 patients with treatment naïve early RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease activity of RA patients was assessed according to the 28-Joint Count Disease Activity Score (DAS28). Results The levels of serum IL-35 were significantly higher in patients with treatment naïve early RA compared to those with established disease and control OA subjects. In addition, serum levels of IL-35 significantly decreased 12 weeks after initiation of glucocorticoids and conventional synthetic disease modifying antirheumatic drugs in patients with treatment naïve early RA. Synovial fluid IL-35 levels were significantly higher in RA compared to OA patients, were significantly elevated compared to serum counterparts and correlated with synovial fluid leukocyte count (r=0.412; p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01). Conclusion This is the first study showing elevated circulating levels of IL-35 in treatment naïve early RA, its significant decrease after treatment initiation and positive association between increased synovial fluid IL-35 and disease activity in patients with long-lasting RA. PMID:26204444

  15. Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastoma

    PubMed Central

    Sonawane, Poonam; Cho, Hwang Eui; Tagde, Ashujit; Verlekar, Dattesh; Yu, Alice L; Reynolds, C Patrick; Kang, Min H

    2014-01-01

    Background and Purpose Isotretinoin (13-cis-retinoic acid; 13-cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high-risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13-cRA treatment. The plasma concentrations of 13-cRA in earlier studies were considered subtherapeutic while 4-oxo-13-cis-RA (4-oxo-13-cRA), a metabolite of 13-cRA considered by some investigators as inactive, were greater than threefold higher than 13-cRA. We sought to define the metabolic pathways of 13-cRA and investigated the anti-tumour activity of its major metabolite, 4-oxo-13-cRA. Experimental Approach Effects of 13-cRA and 4-oxo-13-cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down-regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13-cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples. Key Results Six major metabolites of 13-cRA were identified in patient samples. Of these, 4-oxo-13-cRA was the most abundant, and 4-oxo-13-cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13-cRA to 4-oxo-13-cRA. In human neuroblastoma cell lines, 4-oxo-13-cRA and 13-cRA were equi-effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor-β mRNA and protein levels. Conclusions and Implications We showed that 4-oxo-13-cRA is as active as 13-cRA against neuroblastoma cell lines. Plasma levels of both 13-cRA and 4-oxo-13-cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma. PMID:25039756

  16. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

    PubMed Central

    Doronin, Vasilii B.; Parkhomenko, Taisiya A.; Castellazzi, Massimiliano; Cesnik, Edward; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

    2016-01-01

    We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID:27196086

  17. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

    PubMed

    Doronin, Vasilii B; Parkhomenko, Taisiya A; Castellazzi, Massimiliano; Cesnik, Edward; Buneva, Valentina N; Granieri, Enrico; Nevinsky, Georgy A

    2016-01-01

    We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID:27196086

  18. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    PubMed Central

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. Methods MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Results Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Conclusions Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. Trial registration number NCT01039688; Results. PMID:27493790

  19. Compilation of Spectroscopic Data of Radium (Ra I and Ra II)

    NASA Astrophysics Data System (ADS)

    Dammalapati, U.; Jungmann, K.; Willmann, L.

    2016-03-01

    Energy levels, wavelengths, lifetimes, and hyperfine structure constants for the isotopes of the first and second spectra of radium, Ra I and Ra II, have been compiled. Wavelengths and wavenumbers are tabulated for 226Ra and for other Ra isotopes. Isotope shifts and hyperfine structure constants of even and odd-A isotopes of neutral radium atom and singly ionized radium are included. Experimental lifetimes of the states for both neutral and ionic Ra are also added, where available. The information is beneficial for present and future experiments aimed at different physics motivations using neutral Ra and singly ionized Ra.

  20. Patient Activation and Mental Health Care Experiences Among Women Veterans.

    PubMed

    Kimerling, Rachel; Pavao, Joanne; Wong, Ava

    2016-07-01

    We utilized a nationally representative survey of women veteran primary care users to examine associations between patient activation and mental health care experiences. A dose-response relationship was observed, with odds of high quality ratings significantly greater at each successive level of patient activation. Higher activation levels were also significantly associated with preference concordant care for gender-related preferences (use of female providers, women-only settings, and women-only groups as often as desired). Results add to the growing literature documenting better health care experiences among more activated patients, and suggest that patient activation may play an important role in promoting engagement with mental health care. PMID:25917224

  1. Patient Activation and Mental Health Care Experiences Among Women Veterans

    PubMed Central

    Pavao, Joanne; Wong, Ava

    2016-01-01

    We utilized a nationally representative survey of women veteran primary care users to examine associations between patient activation and mental health care experiences. A dose–response relationship was observed, with odds of high quality ratings significantly greater at each successive level of patient activation. Higher activation levels were also significantly associated with preference concordant care for gender-related preferences (use of female providers, women-only settings, and women-only groups as often as desired). Results add to the growing literature documenting better health care experiences among more activated patients, and suggest that patient activation may play an important role in promoting engagement with mental health care. PMID:25917224

  2. HLA-DRB1 shared epitope genotyping using the revised classification and its association with circulating autoantibodies, acute phase reactants, cytokines and clinical indices of disease activity in a cohort of South African rheumatoid arthritis patients

    PubMed Central

    2011-01-01

    Introduction The revised shared epitope (SE) concept in rheumatoid arthritis (RA) is based on the presence (S) or absence (X) of the SE RAA amino acid motif at positions 72 to 74 of the third hypervariable region of the various human leucocyte antigen (HLA)-DRB1 alleles. The purpose of this study was to investigate SE subtypes on the basis of the American College of Rheumatology 1987 revised criteria for the classification of RA in a cohort of South African RA patients (n = 143) and their association with clinical and circulating biomarkers of disease activity (autoantibodies, acute phase reactants and cytokines). Methods Genomic DNA was analysed using high-resolution recombinant sequence-specific oligonucleotide PCR typing of the HLA-DRB1 allele. Subtypes of the SE were classified according to the amino acids at positions 72 to 74 for the RAA sequence, and further sub-divided according to the amino acids at positions 70 and 71, which either contribute to (S2, S3P), or negate (S1, S3D) RA susceptibility. Disease activity was assessed on the basis of (1) Disease Activity Score in 28 joints using C-reactive protein (CRP), (2) rheumatoid factor (RF), (3) CRP and (4) serum amyloid A by nephelometry, anticyclic citrullinated peptide antibodies (aCCP) by an immunofluorometric procedure, and cytokines by multiplex bead array technology. Results Of the 143 RA patients, 81 (57%) were homozygous (SS) and 50 (35%) were heterozygous (SX) for the SE alleles with significant overexpression of S2 and S3P (respective odds ratios (ORs) 5.3 and 5.8; P < 0.0001), and 12 (8%) were classified as no SE allele (XX). Both the SS and SX groups showed a strong association with aCCP positivity (OR = 10.2 and P = 0.0010, OR = 9.2 and P = 0.0028, respectively) relative to the XX group. Clinical scores and concentrations of the other biomarkers of disease activity (RF, CRP and T helper cell type 1 (Th1), Th2, macrophage and fibroblast cytokines) were also generally higher in the SS group than

  3. The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

    PubMed Central

    Silva, Bruna Daniella Souza; Tannus-Silva, Daniela Graner Schuwartz; Rabahi, Marcelo Fouad; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2013-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world’s population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients. PMID:24626307

  4. 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.

  5. Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study

    PubMed Central

    2011-01-01

    Introduction Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first five years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the five-year follow-up period and the modulatory effect of pharmacological treatment. Methods All patients from the four northern-most counties of Sweden with early RA are, since December 1995, consecutively recruited at diagnosis (T0) into a large survey on the progress of the disease. Information regarding cardiovascular co-morbidity and related predictors was collected from clinical records and supplemented with questionnaires. By April 2008, 700 patients had been included of whom 442 patients had reached the five-year follow-up (T5). Results Among the 442 patients who reached T5 during the follow-up period, treatment for hypertension increased from 24.5 to 37.4% (P < 0.001)), diagnosis of diabetes mellitus (DM) from 7.1 to 9.5% (P < 0.01) whilst smoking decreased from 29.8 to 22.4% (P < 0.001) and the BMI from 26.3 to 25.8 (P < 0.05), respectively. By T5, 48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients died during the follow-up period. Age at disease onset, male sex, a previous CVE, DM, treatment for hypertension, triglyceride level, cumulative disease activity (area under the curve (AUC) disease activity score (DAS28)), extra-articular disease, corticosteroid use, shorter duration of treatment with disease modifying anti-rheumatic drugs (DMARDs) and use of COX-2 inhibitors increased the hazard rate for a new CVE. A raised erythrocyte sedimentation rate (ESR) at inclusion and AUC DAS28 at six months increased the hazard rate of CVE independently whilst DMARD treatment was

  6. Faecal carriage of klebsiella by patients with ankylosing spondylitis and rheumatoid arthritis.

    PubMed Central

    Warren, R E; Brewerton, D A

    1980-01-01

    In consecutive samples submitted to a clinical microbiology laboratory 22 out of 99 from outpatients and 23 out of 51 from inpatients yielded Klebsiella sp. A clinical reassessment of outpatients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) who had not been inpatients within the last year was made for disease activity and drug requirements. 124 patients with AS and 92 with RA were requested at assessment to submit a stool specimen for klebsiella examination, this being carried out without disclosure of the patient's clinical category. Two months later a questionnaire on symptom changes was collected and the results correlated with klebsiella carriage. Eighty-nine patients with AS and 82 patients with RA fulfilled all criteria for assessment. Of those assessed, 24 out of 89 AS patients and 26 out of 82 RA patients had klebsiella in the faeces. There was no correlation betweeh the initial clinical assessment category and klebsiella carriage. Seventy patients with AS and 57 paients with RA had no change in symptoms over the 2-month period. Nineteen AS patients and 31 RA patients noted symptom improvement or worsening. Of these, 3 AS and 10 RA patients had klebsiella in their faeces. There was no correlation between worsening of symptoms over a 2-month period and klebsiella carriage at initial assessment. PMID:7377857

  7. Improving the Measurement of Disease Activity for Patients with Rheumatoid Arthritis: Validation of an Electronic Version of the Routine Assessment of Patient Index Data 3

    PubMed Central

    Chua, Ruthie M.; Mecchella, John N.; Zbehlik, Alicia J.

    2015-01-01

    Introduction. An electronic Routine Assessment of Patient Index Data 3 (RAPID 3) was incorporated into our electronic health records (EHRs) which did not replicate the visual presentation of the paper version. This study validated the electronic RAPID 3 compared to the paper version. Methods. Rheumatoid arthritis (RA) patients (n = 50) completed both the electronic RAPID 3 online in the week prior to and a paper version on the day of their clinic visit. Results. Paired t-test showed no significant difference (p value = 0.46) between versions. Conclusion. The electronic version of RAPID 3 is valid and can be easily integrated in care of RA patients. PMID:26633974

  8. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    PubMed Central

    Romero-Velez, Gustavo; Lisker-Cervantes, Andrés; Villeda-Sandoval, Christian I; Sotomayor de Zavaleta, Mariano; Olvera-Posada, Daniel; Sierra-Madero, Juan Gerardo; Arreguin-Camacho, Lucrecia O; Castillejos-Molina, Ricardo A

    2014-01-01

    Objective To assess the prevalence and risk factors of erectile dysfunction (ED) in HIV patients from the HIV clinic of a tertiary referral center in Mexico City. Design Prevalence was obtained from cross-sectional studies, and the International Index of Erectile Function (IIEF), a standardized method, was used to assess ED. Methods A cross-sectional study was performed in the HIV clinic. Participants completed the IIEF to allow ED assessment. Information on demographics, clinical and HIV-related variables was retrieved from their medical records. Results One hundred and nine patients were included, with a mean age of 39.9 ± 8.8 years. ED was present in 65.1% of the individuals. Patients had been diagnosed with HIV for a mean of 92.7 ± 70.3 months and had undergone a mean 56.4 ± 45.5 months of HAART. The only variable associated with ED in the univariate analysis was dyslipidemia, and this association was also found in the multivariate analysis (P = 0.01). Conclusions ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero-Velez G, Lisker-Cervantes A, Villeda-Sandoval CI, Sotomayor de Zavaleta M, Olvera-Posada D, Sierra-Madero JG, Arreguin-Camacho LO, and Castillejos-Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30. PMID:25356298

  9. 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. PMID:27221456

  10. Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

    ERIC Educational Resources Information Center

    Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

    2013-01-01

    Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

  11. Psychosocial problems among newly diagnosed rheumatoid arthritis patients.

    PubMed

    Gåfvels, C; Hägerström, M; Nordmark, B; Wändell, P E

    2012-03-01

    We identified patients with newly diagnosed rheumatoid arthritis (RA) in the ages 18-65 years who needed psychosocial interventions. A total of 123 patients (90 women) were asked to participate, but 19 declined and 4 dropped out early in the study, leaving a total of 100 patients (75 women) in the sample. Questionnaires used were the Epidemiological Investigation on Rheumatoid Arthritis study questionnaire, the Hospital Anxiety and Depression Scale, the Sense of Coherence (SOC) scale, and the General Coping Questionnaire. Interviews showed that 46% of the included 100 patients had psychosocial problems (PSP). One third of them had problems directly related to RA. The rest had problems with their life situation in general, without or reinforced by RA. Compared to patients without psychosocial problems, PSP patients lived in more strained social situations, especially regarding personal finances and social support. More of the PSP patients were anxious, showed lower SOC scores, and also used more emotion-based coping strategies (resignation, protest, isolation and intrusion) and less problem-oriented (minimization). They also had higher scores on depression and more frequently expected that RA would negatively affect their future. PSP patients also experienced a more negative impact of the disease, a finding not confirmed by the sickness activity score judged by the rheumatologist. Thus, early in the course of RA, screening instruments should be used to identify PSP patients. Psychosocial treatment and support by medical social workers skilled in RA care should be offered. PMID:22089162

  12. Increasing Patient Activation Could Improve Outcomes for Patients with Inflammatory Bowel Disease.

    PubMed

    Shah, Shawn L; Siegel, Corey A

    2015-12-01

    Inflammatory bowel disease (IBD) is a complex disease process that often requires the integration of skills from various health care providers to adequately meet the needs of patients with IBD. The medical and surgical treatment options for IBD have become more complicated and are frequently a source of angst for both the patient and provider. However, it has become more important than ever to engage patients in navigating the treatment algorithm. Although novel in the IBD world, the concept of patients' becoming more active and effective managers of their care has been well studied in other disease processes such as diabetes mellitus and mental illness. This idea of patient activation refers to a patient understanding his or her role in the care process and having the skill sets and self-reliance necessary to manage his or her own health care. Over the past decade, evidence supporting the role of patient activation in chronic illness has grown, revealing improved health outcomes, enhanced patient experiences, and lower overall costs. Patient activation can be measured, and interventions have been shown to improve levels of activation over time and influence outcomes. A focus on patient activation is very appropriate for patients with IBD because this may potentially serve as a tool for IBD providers to not only improve patient outcomes and experience but also reduce health care costs. PMID:26422517

  13. T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in subchondral bone marrow microenvironment of patients with rheumatoid arthritis

    PubMed Central

    Wang, Ting; Li, Shufeng; Yang, Yun; Zhang, Kaining; Dong, Shixiao; Wang, Xiuhua; Liu, Xinguang; Ren, Yanjun; Zhang, Ming; Yan, Xinfeng; Li, Jianmin; Zhang, Lei

    2016-01-01

    Objectives: The present study is to investigate the profiles of Th17, Th1 and Treg cells in bone marrow of patients with rheumatoid arthritis (RA). Methods: Flow cytometry was used to analyze the frequencies of Th17, Th1 and Treg cells in paired peripheral blood and bone marrow of 26 RA patients and 11 osteoarthritis (OA) patients, as well as 10 healthy controls. In addition, the disease activity was analyzed by the 28-joint disease activity score (DAS28). Results: The frequencies of Th17 and Th1 cells were significantly elevated in bone marrow of RA patients. Importantly, Th17 and Th1 cells were significantly elevated in bone marrow compared with the matched peripheral blood from RA patients. However, Treg cells were significantly decreased in bone marrow of RA patients compared with the matched peripheral blood of RA patients and bone marrow of osteoarthritis patients and healthy controls. Moreover, the frequencies of tumor necrosis factor-α-producing T cells were significantly elevated in bone marrow from RA patients. Additionally, Th17 and Th1 cells in bone marrow were positively correlated with DAS28, while Treg cells were negatively correlated with DAS28. Conclusions: The present study demonstrates that Th17 and Th1 cells are markedly increased in bone marrow from RA patients. By contrast, Treg cells are significantly decreased in bone marrow from RA patients. These results suggest that local abnormality of Th17, Th1 and Treg cells in bone marrow of RA patients may contribute to bone destruction in skeletal system. PMID:27508016

  14. RaPToRS Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  15. Sports, Physical Activity and Patient-Reported Outcomes After Medial Unicompartmental Knee Arthroplasty in Young Patients.

    PubMed

    Walker, Tilman; Streit, Julia; Gotterbarm, Tobias; Bruckner, Thomas; Merle, Christian; Streit, Marcus R

    2015-11-01

    One hundred-and-one patients age 60 or younger following medial mobile bearing UKA were reviewed retrospectively with a minimum follow-up of 2 years using the Schulthess activity score, Tegner, UCLA and SF-36 score to assess their level of physical activity and quality of life. Patients showed a rapid recovery and resumption of their activities with a return-to-activity rate of 93%. Most common activities were low impact, whereas high-impact activities showed a significant decrease. Precaution was found to be the main reason for a decrease in the level of activity. The results of this study demonstrate that patients age 60 or younger following medial UKA were able to return to regular physical activities with almost two-thirds of the patients reaching a high activity level (UCLA≥7). PMID:26088397

  16. Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

    PubMed Central

    Kutzbach, Abraham Garcia; Amital, Howard; Pavelka, Karel; Lazaro, María Alicia; Moots, Robert J.; Wollenhaupt, Jürgen; Zerbini, Cristiano A. F.; Louw, Ingrid; Combe, Bernard; Beaulieu, Andre; Schulze-Koops, Hendrik; Dasgupta, Bhaskar; Fu, Bo; Huyck, Susan; Weng, Haoling H.; Govoni, Marinella; Durez, Patrick

    2016-01-01

    Objective. To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. Methods. We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. Results. In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648–0.809 (R2 = 0.0397–0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. Conclusion. A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy. PMID:27114562

  17. Determination of (226)Ra, (232)Th, (40)K, (235)U and (238)U activity concentration and public dose assessment in soil samples from bauxite core deposits in Western Cameroon.

    PubMed

    Mekongtso Nguelem, Eric Jilbert; Moyo Ndontchueng, Maurice; Motapon, Ousmanou

    2016-01-01

    Determination of activity concentrations in twenty five (25) soil samples collected from various points in bauxite ore deposit in Menoua Division in Western of Cameroon was done using gamma spectrometry based Broad Energy Germanium (BEGe6530) detector. The average terrestrial radionuclides of (40)K, (226)Ra, (232)Th, (235)U and (238)U were measured as 671 ± 272, 125 ± 58, 157 ± 67, 6 ± 3 and 99 ± 69 Bq kg(-1), respectively. The observed activity concentrations of radionuclides were compared with other published values in the world. The outdoor absorbed dose rate in air varied from 96.1 to 321.2 nGy h(-1) with an average of 188.2 ± 59.4 nGy h(-1). The external annual effective dose rate and external hazard index were estimated as 0.23 ± 0.07 mSv year(-1) for outdoor, 0.92 ± 0.29 mSv year(-1) for indoor and 1.13 for the external hazard index, respectively. These radiological safe parameters were relatively higher than the recommended safe limits of UNSCEAR. Consequently, using of soil as building material might lead to an increase the external exposure to natural radioactivity and future applications research need to be conducted to have a global view of radioactivity level in the area before any undergoing bauxite ore exploitation. PMID:27536536

  18. Lower paraoxonase 1 activity in Tunisian bipolar I patients

    PubMed Central

    2010-01-01

    Background The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. Patients and methods Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific). Results Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels. Conclusions Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile. PMID:20964824

  19. Rapid determination of 226Ra in environmental samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.

    2012-02-04

    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}Ac 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.

  20. Circulating thymic hormone activity in young cancer patients.

    PubMed Central

    Consolini, R; Cei, B; Cini, P; Bottone, E; Casarosa, L

    1986-01-01

    We measured serum levels of Facteur Thymique Sérique (FTS) in 56 young cancer patients compared to normal controls. All patients who received immunosuppressive therapy had low age-corrected titres of FTS. Low levels were also found at diagnosis and off therapy. Plasma from 22 patients contained factors capable of inhibiting biological activity of FTS in vitro. The nature of this inhibitor has not been elucidated. No zinc deficiency was found in the patients studied, suggesting that FTS is secreted in its active form. Our study points out the importance of monitoring FTS activity in young cancer patients for its implications on immunological surveillance. The practical applications of thymic hormone therapy in cancer patients are discussed. PMID:3802571

  1. [Uptake of radionuclides from soil to plant and the discovery of 226Ra, 232Th hyperaccumulator].

    PubMed

    Zhang, Zhi-Qiang; Chen, Di-Yun; Song, Gang; Yue, Yu-Mei

    2011-04-01

    11 sorts of plant samples and corresponding soil samples were collected in Conghua and Taishan, Pearl River Delta. The specific activity of 238U, 226Ra, 232Th and 40K of samples were investigated by using HPGe-gamma-ray spectra analysis. The results showed that the average specific activity of 238U, 226Ra, 232Th and 40K in soil samples were 151.8, 146.3, 226.6, 665.5 Bq/kg, which were higher than the average values of China and the world. The concentration of 238U in all sort of plants are very low and most of them are lower than detection limit, while the values of 226Ra, 232Th and 40K were high. The contents of 226Ra and 232Th in Dicranopteris dichotoma were the highest, whose average specific activity is 285.9, 986.2 Bq/kg respectively. The average bioconcentration factors (BFs)of 26Ra, 232Th of Dicranopteris dichotoma were 2.20, 4.23, respectively, the other 10 sort of plants have BFs of 2266Ra, 232Th were in the range of 10(-1)-10(-2). The bioconcentration factors and the translocation factors of 226Ra, 232Th of Dicranopteris dichotoma. were all bigger than 1, so Dicranopteris dichotoma can be defined as hyperaccumulator of 226Ra and 232Th. PMID:21717763

  2. Sexual activity among patients in psychiatric hospital wards.

    PubMed

    Warner, James; Pitts, Nicola; Crawford, Mike J; Serfaty, Marc; Prabhakaran, Pramod; Amin, Rizkar

    2004-10-01

    In psychiatric hospitals, sexual activity between patients raises special difficulties regarding consent. We undertook a questionnaire survey of inpatients in the mental health units of three hospitals to identify the nature and frequency of sexual activity. A contemporaneous staff questionnaire was used in an attempt to validate the patient reports. Of the 100 patients who participated (response rate 60%), 30 reported engaging in some form of sexual activity including 10 who had sexual intercourse. All sexual intercourse was consensual, but only 2 respondents used condoms. Staff questionnaires suggested levels of sexual activity congruent with patient reports. This survey underlines the conflict between an individual's right to sexual expression and the need to protect vulnerable patients. PMID:15459258

  3. Sialyltransferase and Neuraminidase Levels/Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study

    PubMed Central

    Liou, Lieh-bang; Huang, Che-ching

    2016-01-01

    Objective We attempted to determine whether the level of enzymes sialyltransferase (ST) and neuraminidase (Neu) and sialic acid (SIA) in patients with systemic lupus erythematosus (SLE) correlates with the SLE Disease Activity Index (SLEDAI) and in patients with rheumatoid arthritis (RA) correlates with the Disease Activity Score28 (DAS28). Methods We examined cell-surface levels of ST6Gal-1, Neu1, ST3Gal-1, Neu3, α-2,6-SIA, and α-2,3-SIA by using fluorescent anti-enzyme antibodies, fluorescent-conjugated Sambucus nigra lectin, and fluorescent-conjugated Maackia amurensis lectin on blood cells in SLE and RA patients and assessed correlations of these levels with SLEDAI and with DAS28. Areas under the curve (AUC) were calculated for different variables against SLEDAI. Results The B-cell ST3Gal-1/Neu3 ratio positively correlated with SLEDAI scores (ρ = 0.409 and P = 0.002, statistically significant after Bonferroni’ correction for multiple analyses.). It was supported by the inverse correlation of B-cell Neu3 levels with SLEDAI scores (ρ = −0.264, P = 0.048). The B-cell ST3Gal-1/Neu3 ratio against SLEDAI yielded an AUC of 0.689, which was comparable to that of anti-dsDNA levels at 0.635. In contrast, both ST3Gal-1 and Neu3 levels of RA B cells (r = 0.376, P = 0.013; r = 0.425, P = 0.005, respectively) correlated positively with high disease-activity DAS28 scores. Conclusion B-cell ST3Gal-1/Neu3 ratios in SLE and B-cell ST3Gal-1 and Neu3 levels in RA with high disease-activity DAS28 scores correlated with disease activity measures and may be useful in monitoring disease activities. PMID:26981635

  4. Recommendations for physical activity in patients with multiple sclerosis.

    PubMed

    Petajan, J H; White, A T

    1999-03-01

    For many years, patients with multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system, have been advised to avoid exercise. MS is believed to be autoimmune in origin, mediated by activated T cells which penetrate the blood-brain barrier and attack myelin. The pathophysiology, with respect to function is an impairment of saltatory conduction, specifically, slowing of conduction speed and/or conduction block. Symptoms can temporarily worsen on exposure to heat or during physical exercise. Exercise programmes must be designed to activate working muscles but avoid overload that results in conduction block. Fatigue, often severe, affects about 85% of MS patients and, along with motor and sensory symptoms, results in decreased mobility and reduced quality of life. Physical activity and recreation are reduced in patients with MS. Before developing recommendations, physical activity patterns and the physical effects of MS should be assessed in individual patients. Patients may then be functionally classified. Physical activity can also be classified in a pyramid structure, with the most basic functions forming the base and the most integrated functions on top. The muscular fitness pyramid progresses through passive range of motion, active resistive, specific strengthening and integrated strength exercises Overall physical activity may be increased according to functional level by performing activities of daily living, incorporating inefficiencies into daily living, pursuing more active recreation and eventually developing a structured exercise programme. The importance of the proper exercise environment, balance and coordination issues and factors related to adherence are discussed. PMID:10222541

  5. Plasma thymic hormone activity in patients with chronic mucocutaneous candidiasis

    PubMed Central

    Kirkpatrick, C. H.; Greenberg, Lynn E.; Chapman, S. W.; Goldstein, G.; Lewis, Verna M.; Twomey, J. J.

    1978-01-01

    To further characterize the immunological abnormalities in patients with chronic mucocutaneous candidiasis, the thymic hormone activity in their plasma was measured. Of the sixteen patients in the study, seven had chronic diffuse candidiasis, five had candidiasis with endocrinopathies and four had candidiasis with thymoma. Only one patient, an anergic child with chronic diffuse candidiasis had severe deficiency of plasma thymic hormone activity. Two patients, a woman with candidiasis and multiple endocrinopathies and an elderly man with metastatic epithelial thymoma had supranormal values. These studies indicate that the immunological deficit in most patients with these forms of chronic mucocutaneous candidiasis is not due to deficiency of a thymic inductive activity and suggest that an intrinsic defect exists in the maturation of antigen-responsive lymphoid cells. PMID:743805

  6. Inadvertant hypothermia and active warming for surgical patients.

    PubMed

    Tanner, Judith

    Inadvertant hypothermia is common among surgical patients and can result in serious complications. This article describes active warming systems which can be used preoperatively and intraoperatively to prevent hypothermia and maintain normothermia (normal body temperature). PMID:22067488

  7. Variables associated with patient activation in persons with multiple sclerosis.

    PubMed

    Goodworth, Marie-Christine R; Stepleman, Lara; Hibbard, Judith; Johns, Lisa; Wright, Dustin; Hughes, Mary D; Williams, Mitzi J

    2016-01-01

    Identifying variables associated with patient activation in the multiple sclerosis population could serve to facilitate better multiple sclerosis self-management behaviors. Using a cross-sectional survey design, 199 participants were recruited from a multiple sclerosis center in the Southeastern United States. Depression, multiple sclerosis quality of life, and multiple Sclerosis self-efficacy were all significantly correlated with patient activation. Results of a hierarchical regression indicated that patient activation was significantly related to educational attainment, depression, and self-efficacy but not to quality of life. The results suggest several possible targets for intervention to increase patient activation, including health literacy, depression symptoms, and self-efficacy for multiple sclerosis disease management. PMID:24591120

  8. Glycan Biomarkers for Rheumatoid Arthritis and Its Remission Status in Han Chinese Patients.

    PubMed

    Sebastian, Andrea; Alzain, Mohamed Ali; Asweto, Collins Otieno; Song, Haicheng; Cui, Liufu; Yu, Xinwei; Ge, Siqi; Dong, Hao; Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; He, Dian; Guo, Xiuhua; Song, Manshu; Wang, Youxin; Wang, Wei

    2016-06-01

    Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p < 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA. PMID:27310476

  9. Discrepancies in assessment of patients with rheumatoid arthritis and secondary Sjögren's syndrome by DAS28-ESR and DAS28-CRP

    PubMed Central

    Olesińska, Marzena; Paradowska-Gorycka, Agnieszka; Mańczak, Małgorzata; Felis-Giemza, Anna; Wojdasiewicz, Piotr; Szukiewicz, Dariusz

    2016-01-01

    Objectives To investigate whether a difference exists between DAS28 from CRP and DAS28 from ESR in patients with rheumatoid arthritis (RA) and secondary Sjögren's syndrome (sSS). Material and methods One group comprised patients with RA and sSS, the control group comprised patients with RA. The inclusion criteria for the RA and sSS group have been specified as follows: presence of at least one symptom of dryness, and also presence of anti-SS-A and anti-SS-B or at least focus score of one in biopsy. Results The disease activity score 28 (DAS28) was assessed using both ESR and CRP in 60 patients with RA and sSS and 59 patients with RA alone. However, concordance between these two methods was good (Cohen's κ coefficient κ = 0.60, 95% CI: 0.45-0.75 in the first group and κ = 0.71, 95% CI: 0.56-0.86 in the control group). In the group with RA and sSS, the mean value of DAS28-ESR = 5.2, whereas the mean value of DAS28-CRP = 4.7 (p < 0.0001). In the group with RA alone, mean DAS28-ESR = 4.7 while mean DAS28-CRP = 4.6; no significant difference was identified. Moreover, in RA patients with sSS, mean ESR = 39 mm/h compared with mean CRP at 25 mg/l. 79% of all patients demonstrated dysproteinaemia. There were connections between higher ESR and dysproteinaemia. In the control group there was no statistically significant difference between CRP and ESR. Conclusions Both DAS28-ESR and DAS28-CRP are useful outcome measures in RA. However, in patients with RA and sSS, DAS28 should be evaluated based on CRP. PMID:27536205

  10. Management of Hypertension: Adapting New Guidelines for Active Patients.

    ERIC Educational Resources Information Center

    Tanji, Jeffrey L.; Batt, Mark E.

    1995-01-01

    Discusses recent guidelines on hypertension from the National Heart, Lung, and Blood Institute and details the latest management protocols for patients with high blood pressure. The article helps physicians interpret the guidelines for treating active patients, highlighting diagnosis, step care revision, pharmacology, and sports participation…

  11. Pain Sensitisation in Women with Active Rheumatoid Arthritis: A Comparative Cross-Sectional Study

    PubMed Central

    Vladimirova, Nora; Jespersen, Anders; Bartels, Else Marie; Christensen, Anton W.; Bliddal, Henning; Danneskiold-Samsøe, Bente

    2015-01-01

    Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA (DAS28 > 2.6) and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold (p < 0.01) and pain tolerance (p < 0.01) than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (p < 0.01). Conclusion. Patients with active RA showed decreased pressure-pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies. PMID:26266046

  12. Pain Sensitisation in Women with Active Rheumatoid Arthritis: A Comparative Cross-Sectional Study.

    PubMed

    Vladimirova, Nora; Jespersen, Anders; Bartels, Else Marie; Christensen, Anton W; Bliddal, Henning; Danneskiold-Samsøe, Bente

    2015-01-01

    Objectives. In some rheumatoid arthritis (RA) patients, joint pain persists without signs of inflammation. This indicates that central pain sensitisation may play a role in the generation of chronic pain in a subgroup of RA. Our aim was to assess the degree of peripheral and central pain sensitisation in women with active RA compared to healthy controls (HC). Methods. 38 women with active RA (DAS28 > 2.6) and 38 female HC were included in, and completed, the study. Exclusion criteria were polyneuropathy, pregnancy, and no Danish language. Cuff Pressure Algometry measurements were carried out on the dominant lower leg. Pain threshold, pain tolerance, and pain sensitivity during tonic painful stimulation were recorded. Results. Women with active RA had significantly lower pain threshold (p < 0.01) and pain tolerance (p < 0.01) than HC. The mean temporal summation- (TS-) index in RA patients was 0.98 (SEM: 0.09) and 0.71 (SEM: 0.04) in HC (p < 0.01). Conclusion. Patients with active RA showed decreased pressure-pain threshold compared to HC. In addition, temporal summation of pressure-pain was increased, indicating central pain sensitization, at least in some patients. Defining this subgroup of patients may be of importance when considering treatment strategies. PMID:26266046

  13. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-01-01

    Objective Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. Methods The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Results Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). Conclusion The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD. PMID:27482243

  14. Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures

    PubMed Central

    Kremer, Joel M; Lawrence, David A; Hamilton, Robert; McInnes, Iain B

    2016-01-01

    Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. Design Prospective, open-label, long-term mechanism of action study. Setting University clinic. Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007). Conclusions MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion. PMID:27335660

  15. Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis

    SciTech Connect

    Duby, A.D.; Sinclair, A.K.; Osborne-Lawrence, S.L. ); Zeldes, W.; Kan, Li; Fox, D.A. )

    1989-08-01

    Although substantial evidence suggests that synovial T lymphocytes are critical in the pathogenesis of rheumatoid arthritis (RA), little is known regarding their antigenic specificities, antigen receptor gene rearrangements, and mechanisms of activation. To assess the extend of expansion of specific clones among RA synovial fluid T cells, Southern blot analyses of T-cell receptor (TCR) gene rearrangements were performed on 40 RA synovial fluid T-cell clones, as well as on fresh and polyclonally activated T cells from RA synovial fluid, RA peripheral blood, and normal peripheral blood. Two of the clones had identical TCR rearrangement patterns, but the remainder were unique. The nonclonal RA T-cell samples showed the same pattern of TCR {beta}-chain rearrangement that was observed among normal peripheral blood T cells, indicating no dominant clonal T-cell population in these samples. It was noted that with sufficient exposure of autoradiograms of the Southern blots, discrete TCR gene rearrangements, representing in some cases common D{sub {beta}}J{sub {beta}} (D, diversity; J, joining) rearrangements, were evident in T cells from peripheral blood of normal individuals and patients with RA, as well as T cells from RA synovial fluid. Taken together, the findings indicate that only a minor degree of oligoclonality can be demonstrated among T lymphocytes from RA synovial fluid.

  16. Complement Activation in Patients with Focal Segmental Glomerulosclerosis

    PubMed Central

    Thurman, Joshua M.; Wong, Maria; Renner, Brandon; Frazer-Abel, Ashley; Giclas, Patricia C.; Joy, Melanie S.; Jalal, Diana; Radeva, Milena K.; Gassman, Jennifer; Gipson, Debbie S.; Kaskel, Frederick; Friedman, Aaron; Trachtman, Howard

    2015-01-01

    Background Recent pre-clinical studies have shown that complement activation contributes to glomerular and tubular injury in experimental FSGS. Although complement proteins are detected in the glomeruli of some patients with FSGS, it is not known whether this is due to complement activation or whether the proteins are simply trapped in sclerotic glomeruli. We measured complement activation fragments in the plasma and urine of patients with primary FSGS to determine whether complement activation is part of the disease process. Study Design Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants We identified 19 patients for whom samples were available from weeks 0, 26, 52 and 78. The results for these FSGS patients were compared to results in samples from 10 healthy controls, 10 patients with chronic kidney disease (CKD), 20 patients with vasculitis, and 23 patients with lupus nephritis. Outcomes Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results Plasma and urine Ba, C4a, sC5b-9 were significantly higher in FSGS patients at the time of diagnosis than in the control groups. Plasma Ba levels inversely correlated with the eGFR at the time of diagnosis and at the end of the study. Plasma and urine Ba levels at the end of the study positively correlated with the level of proteinuria, the primary outcome of the study. Limitations Limited number of patients with samples from all time-points. Conclusions The complement system is activated in patients with primary FSGS, and elevated levels of plasma Ba correlate with more severe disease. Measurement of complement fragments may identify a subset of patients in whom the complement system is activated. Further investigations are needed to confirm our findings and to determine the prognostic significance of

  17. Synchronization of EEG activity in patients with bipolar disorder

    NASA Astrophysics Data System (ADS)

    Panischev, O. Yu; Demin, S. A.; Muhametshin, I. G.; Demina, N. Yu

    2015-12-01

    In paper we apply the method based on the Flicker-Noise Spectroscopy (FNS) to determine the differences in frequency-phase synchronization of the cortical electroencephalographic (EEG) activities in patients with bipolar disorder (BD). We found that for healthy subjects the frequency-phase synchronization of EEGs from long-range electrodes was significantly better for BD patients. In BD patients a high synchronization of EEGs was observed only for short-range electrodes. Thus, the FNS is a simple graphical method for qualitative analysis can be applied to identify the synchronization effects in EEG activity and, probably, may be used for the diagnosis of this syndrome.

  18. Management of patients with active caries.

    PubMed

    Milgrom, Peter

    2014-07-01

    This paper reports on a mechanism to manage caries as a disease and to medically intervene in the disease process to halt progression. The goal of this paper is to provide this alternative to a surgical-only approach. The management of caries begins with assessing lesion activity and the potential for arrest. This requires a clinical and radiological assessment and evaluation of risk. Hopeless teeth are extracted and large cavities filled to reduce infection. Risk reduction strategies are employed so efforts to arrest lesions can be successful. Teeth with lesions in the enamel or outer third of the dentin should be sealed, not restored, as restorations can weaken teeth and can be traumatic to pulps. PMID:25076627

  19. 238U- 230Th- 226Ra disequilibrium in young Mt. Shasta andesites and dacites

    NASA Astrophysics Data System (ADS)

    Volpe, Alan M.

    1992-11-01

    The paper describes 238U-series nuclides and 230Th/ 232Th ratios measured by mass spectrometry in mineral separates of young Mt. Shasta andesites and dacites. The results constrain the timing of recent calc-alkaline magma fractionation at this volcano. Hotlum, Misery Hill and Black Butte rocks show small, < 13% 230Th- 238U and < 6% 226Ra- 230Th, disequilibria. Plagioclase have 7-26% 226Ra excesses, magnetite and groundmass have 4-5% 226Ra deficits, and pyroxenes have equilibrium ( 226Ra/ 230Th) activity ratios. Internal ( 230Th)-( 238U)and Ba-normalized ( 226Ra)-( 230Th) isotope diagrams for Hotlum and Black Butte dacites suggest that closed-system Th-U and Ra-Th fractionation occurred less than 10,000 years ago. Significant 226Ra- 230Th disequilibria in the Black Butte dacite strongly suggests that this rock erupted more recently than 9400 years ago. Results for Hotlum andesites suggest a longer pre-eruption crystal residence time compared to the dacites. There may also have been recent open Ra-Th system changes in the melt composition. Initial Th/U ratios for the rocks are low (2.43-2.57), similar to those in mid-ocean ridge basalts (MORB), and preclude significant assimilation of crust with markedly different Th-U composition.

  20. Nuclear structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L. M.; Borge, M. J. G.; Lopez-Jimenez, M. J.; Teijeiro, A. G.; Aas, A. J.; Hageboe, E.; Fogelberg, B.; Mach, H.; Garcia-Raffi, L. M.; Martinez, T.; Rubio, B.; Tain, J. L.; Grant, I. S.; Gulda, K.; Kurcewicz, W.; Loevhoeiden, G.; Tengblad, O.; Thorsteinsen, T. F.

    1999-11-16

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr-Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  1. Nuclear Structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L.M.; Borge, M.J.G.; Aas, A.J.; Fogelberg, B.; Garcia-Raffi, L.M.; Grant, I.S.; Gulda, K.; Hagebo, E.; Kurcewicz, W.; Lopez-Jimenez, M.J.; Lovhoiden, G.; Mach, H.; Martinez, T.; Rubio, B.; Tain, J.L.; Teijeiro, A.G.; Tengblad, O.; Thorsteinsen, T.F.

    1999-12-31

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr - Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  2. Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis

    PubMed Central

    Park, Yune-Jung; Yoo, Seung-Ah; Hwang, Daehee; Cho, Chul-Soo; Kim, Wan-Uk

    2016-01-01

    To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates—gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)—in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals. PMID:26915672

  3. Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis.

    PubMed

    Park, Yune-Jung; Yoo, Seung-Ah; Hwang, Daehee; Cho, Chul-Soo; Kim, Wan-Uk

    2016-01-01

    To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals. PMID:26915672

  4. 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

  5. Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer

    PubMed Central

    Gomes, Edimar Pedrosa; Reboredo, Maycon Moura; Carvalho, Erich Vidal; Teixeira, Daniel Rodrigues; Carvalho, Laís Fernanda Caldi d'Ornellas; Filho, Gilberto Francisco Ferreira; de Oliveira, Julio César Abreu; Sanders-Pinheiro, Helady; Chebli, Júlio Maria Fonseca; de Paula, Rogério Baumgratz; Pinheiro, Bruno do Valle

    2015-01-01

    Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity. PMID:26090432

  6. Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer.

    PubMed

    Gomes, Edimar Pedrosa; Reboredo, Maycon Moura; Carvalho, Erich Vidal; Teixeira, Daniel Rodrigues; Carvalho, Laís Fernanda Caldi d'Ornellas; Filho, Gilberto Francisco Ferreira; de Oliveira, Julio César Abreu; Sanders-Pinheiro, Helady; Chebli, Júlio Maria Fonseca; de Paula, Rogério Baumgratz; Pinheiro, Bruno do Valle

    2015-01-01

    Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity. PMID:26090432

  7. [Creative arts activity in manually handicapped patients].

    PubMed

    Wolf, N

    1986-02-01

    Congenital or acquired conditions directly or indirectly causal in total or partial impairment of manual function are set out. The possibilities for creative-expressive activity, using various techniques, nothwithstanding manual disabilities are pointed out. In Cefischer, who until his war-related loss of both upper limbs had been a renowned cartoonist, a comparison of his works, drawn initially by hand and later with the mouth, reveals his characteristic style of expression having remained the same. Further examples are given of creative expression in the presence of manual disability even under extreme circumstances (such as 11 years of confinement to the Iron Lung). Arts and crafts work of persons with leprosy-related manual handicaps are mentioned; typewriter graphics as a method inaugurated by Basset is presented as used in young people with total manual disability. Partial disability of manual function due to arthritis was present in Renoir, Jawlensky, and Grandma Moses, the course of their conditions is described over time. Contents and form of their pictures, after long years of being manually disabled, do not reveal any essential changes in comparison to their earlier ones. PMID:2938233

  8. Plasma and Synovial Fluid TrxR Levels are Correlated With Disease Risk and Severity in Patients With Rheumatoid Arthritis

    PubMed Central

    Xie, Zhijun; Sun, Jing; Li, Haichang; Shao, Tiejuan; Wang, Dawei; Zheng, Qi; Wen, Chengping

    2016-01-01

    Abstract This study was designed and performed to establish the relationship between plasma and synovial fluid (SF) levels of thioredoxin reductase (TrxR) and disease activity in Chinese patients with rheumatoid arthritis (RA). This study consisted of a total of 224 patients diagnosed with RA, 224 age and sex-matched healthy controls, and 156 patient controls. The disease activity of RA patients was calculated as diseases activity score that include 28-joint counts (DAS 28), which was divided into low-diseases activity (LDA) and high-diseases activity (HDA) groups. Increased plasma TrxR was detected in patients with RA than healthy controls (P < 0.0001). With an area under the curve (AUC) of 0.874, plasma TrxR showed a evidently greater discriminatory ability than C-reactive protein (CRP; AUC, 0.815), antistreptolysin-O (ASO; AUC, 0.631), rheumatoid factor (RF, AUC, 0.793), and erythrocyte sedimentation rate (ESR, AUC, 0.789) in diagnosing RA. RA patients with HDA had significantly elevated TrxR levels in plasma and SF than did those with LDA (P < 0.0001). With an AUC of 0.874, plasma TrxR levels as an indicator for screening of HDA showed a significantly greater discriminatory ability than CRP (AUC, 0.690), ASO (AUC, 0.597), RF (AUC, 0.657), and ESR (AUC, 0.603). Similarly, SF TrxR levels as an indicator for screening of HDA also showed a significantly greater discriminatory ability as compared with above biomarkers. TrxR levels in plasma and SF were positively correlated with the severity of RA. TrxR levels may therefore serve as a new biomarker in addition of the traditional biomarkers for assessing the risk and severity of RA. Further analysis of TrxR release machinery may give us a new understanding of pathogenesis of RA. PMID:26871773

  9. Procoagulant activity in patients with sickle cell trait.

    PubMed

    Lawrie, Andrew S; Pizzey, Arnold; Trompeter, Sara; Meiselman, Herbert; Mohandas, Narla; Dumanski, Jan P; Westerman, Maxwell P

    2012-06-01

    Patients with sickle cell trait (STr) are usually considered to be asymptomatic. However, complications, including hypercoagulability, increased risk of venous thromboembolism and the exertional exercise syndrome with rhabdomyolysis and sudden death, have been described. The exact cause of these adverse events is unclear. We have investigated two patients, a set of monozygotic twins with STr, to establish their procoagulant activity status as a potential indicator of thrombotic risk. In-vivo thrombin generation was assessed by the measurement of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT). D-dimer was used as a marker of fibrinolytic activity. The potential to generate thrombin was determined using an ex-vivo thrombin generation test (TGT). The impact of red blood cell (RBC)-derived microparticle shedding and RBC rheology were examined. TAT (>60 μg/l) and F1 + 2 (948 pmol/l) were markedly elevated in patient 2 but within the normal reference range in patient 1 (TAT = 2.5 μg/l; F1 + 2 = 138 pmol/l). D-dimer levels (0.9 mg/l FEU) were similarly elevated in both patients. TGT peak thrombin and endogenous thrombin potential (ETP) were elevated to similar degrees in both patients. Flow cytometric analysis for RBC-derived microparticles showed that both patients had elevated levels on two occasions. RBC deformability, blood viscosity and RBC aggregation were normal and similar in both patients. The results demonstrated different coagulation activity in the patients with one patient in a prothrombotic state, suggesting that there may be two levels of hypercoagulability in STr. Measurement of such differences would allow for separation of high and low-risk patients from serious complications. PMID:22343687

  10. Development of the Patient Activation Measure for mental health.

    PubMed

    Green, Carla A; Perrin, Nancy A; Polen, Michael R; Leo, Michael C; Hibbard, Judith H; Tusler, Martin

    2010-07-01

    Our objective was to adapt the physical health Patient Activation Measure (PAM) for use among people with mental health conditions (PAM-MH). Data came from three studies among people with chronic mental health conditions and were combined in Rasch analyses. The PAM-MH's psychometric properties equal those of the original 13-item PAM. Test-retest reliability and concurrent validity were good, and the PAM-MH showed sensitivity to change. The PAM-MH appears to be a reliable and valid measure of patient activation among individuals with mental health problems. It appears to have potential for use in assessing change in activation. PMID:19728074

  11. Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk

    PubMed Central

    Cavanillas, María L; Alcina, Antonio; Núñez, Concepción; de las Heras, Virginia; Fernández-Arquero, Miguel; Bartolomé, Manuel; de la Concha, Emilio G; Fernández, Oscar; Arroyo, Rafael; Matesanz, Fuencisla; Urcelay, Elena

    2010-01-01

    Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (PMantel–Haenszel, odds ratio (OR)M–H (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65–0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06–1.34); for rs41295061: 0.03, 0.77 (0.60–0.98)); showed a trend for association of the IL2/IL21 rs6822844 (PM–H=0.07, ORM–H (95% CI)=0.86 (0.73–1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation. PMID:20179739

  12. Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity

    PubMed Central

    Goudy, Kevin; Aydin, Didem; Barzaghi, Federica; Gambineri, Eleonora; Vignoli, Marina; Mannurita, Sara Ciullini; Doglioni, Claudio; Ponzoni, Maurilio; Cicalese, Maria Pia; Assanelli, Andrea; Tommasini, Alberto; Brigida, Immacolata; Dellepiane, Rosa Maria; Martino, Silvana; Olek, Sven; Aiuti, Alessandro; Ciceri, Fabio; Roncarolo, Maria Grazia; Bacchetta, Rosa

    2013-01-01

    Cell-surface CD25 expression is critical for maintaining immune function and homeostasis. As in few reported cases, CD25 deficiency manifests with severe autoimmune enteritis and viral infections. To dissect the underlying immunological mechanisms driving these symptoms, we analyzed the regulatory and effector T cell functions in a CD25 deficient patient harboring a novel IL2RA mutation. Pronounced lymphoproliferation, mainly of the CD8+ T cells, was detected together with an increase in T cell activation markers and elevated serum cytokines. However, Ag-specific responses were impaired in vivo and in vitro. Activated CD8+STAT5+ T cells with lytic potential infiltrated the skin, even though FOXP3+ Tregs were present and maintained a higher capacity to respond to IL-2 compared to other T-cell subsets. Thus, the complex pathogenesis of CD25 deficiency provides invaluable insight into the role of IL2/IL-2RA-dependent regulation in autoimmunity and inflammatory diseases. PMID:23416241

  13. Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFα blockers

    PubMed Central

    Gomes, Carina Mori Frade; Terreri, Maria Teresa; de Moraes-Pinto, Maria Isabel; Barbosa, Cássia; Machado, Natália Pereira; Melo, Maria Roberta; Pinheiro, Marcelo Medeiros

    2015-01-01

    Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)α blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNF α blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNF α therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNF α blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI. PMID:26560983

  14. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  15. Additive Effects of Retinoic Acid (RA) and Bone Morphogenetic Protein 4 (BMP-4) Apoptosis Signaling in Retinoblastoma Cell Lines

    PubMed Central

    Müller, Patrick; Doliva, Rebekka; Busch, Maike; Philippeit, Claudia; Stephan, Harald; Dünker, Nicole

    2015-01-01

    Retinoids have been shown to serve promising therapeutic agents for human cancers, e.g. the treatment of neuroblastoma. Synthetic retinoids, specific for particular retinoic acid (RA) receptors, are tested as new therapy strategies. In the present study, application of recombinant retinoic acid (RA) lowers retinoblastoma (RB) cell viability and induces apoptosis in RB cell lines. Combined treatment of RA and bone morphogenetic protein 4 (BMP-4) increases the pro-apoptotic effect of RA in the RB cells lines WERI-Rb1, Y-79, RB355, RBL-30 and RBL-15, indicating an additive effect. We could show that in WERI-Rb1 cells RA/BMP-4 mediated cell death is at least partially caspase-dependent, whereby RA and BMP-4 additively increased (i) Apaf-1 mRNA levels, (ii) caspase-9 cleavage activity and (iii) the number of activated, cleaved caspase-3 positive cells. Compared to single application of RA and BMP-4, combined RA/BMP-4 treatment significantly augments mRNA levels of the retinoic acid receptors (RARs) RARα and RARß and the retinoic X receptor (RXR) RXRγ suggesting an interaction in the induction of these RA receptor subtypes in WERI-Rb1 cells. Agonist studies revealed that both, RARs and RXRs are involved in RA/BMP-4 mediated apoptosis in WERI-Rb1 retinoblastoma cells. Employing specific RAR subtype antagonists and a RXRß and RXRγ knockdown, we proved that RA/BMP-4 apoptosis signaling in WERI-Rb1 cells requires the RA receptor subtypes RARα, RARß, RXRß and RXRγ. Deciphering signaling mechanisms underlying apoptosis induction of RA and BMP-4 in WERI-Rb1 cells, our study provides useful starting-points for future retinoid-based therapy strategies in retinoblastoma. PMID:26173116

  16. [Physical activity in patients with microvascular complications of diabetes].

    PubMed

    Matoulek, Martin

    2015-04-01

    Physical activity is often underestimated and little used in the treatment of diabetes. The fear of damage, especially in patients with diabetes complications is one of the reasons why it occurs. Physical activity plays an important role in prevention of the progression of peripheral neuropathy and its impact is primarily on the development of muscle strength and the ability to replace the function of nerve fibers damaged disabilities. Demonstrable effect on neuropathy is already recorded a few weeks of regular exercise, long-term programs then demonstrate the safety of occurrence of ulcers in compliance with basic foot care. Present autonomic neuropathy cannot predict response to cardiac respectively, heart rate and blood pressure. Due to other risks (silent ischemia, arrhythmia etc.), it is appropriate to stress test before a prescription of exercise programs. Monitoring of blood pressure, heart rate and blood glucose during the first hours of physical activity is necessary. In patients with autonomic neuropathy of the gastrointestinal tract may significantly affect the composition of the diet not only the ability of physical activity, but can also affect hypoglycaemia due to a slow carbohydrate absorption in these patients. Another risk in patients with autonomic neuropathy is orthostatic hypotension, which may potentiate antihypertensive drugs in "white coat" hypertension. Prescription of patients with retinopathy depends on the form and degree of retinopathy. Only proliferative retinopathy can significantly reduce exercise prescription, and it is always necessary to consult with ophthalmologist. In patients with nephropathy is an important stage of renal insufficiency for prescription of physical activity. Prescription is then influenced by the degree of renal insufficiency in addition to the presence of other associated diseases (anemia, hypertension, osteopathy etc.). Physical activity is essential in patients on dialysis respectively. After renal

  17. Association Between Rectus Abdominis Denervation and Ventilation Dysfunction in Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Zhang, Hua-Gang; Zhang, Shuo; Xu, Ying-Sheng; Zhang, Nan; Fan, Dong-Sheng

    2016-01-01

    Background: Spontaneous potentials in electromyography (EMG) of paraspinal muscles are associated with diaphragm denervation and, therefore, poor respiratory function in amyotrophic lateral sclerosis (ALS) is understandable. EMG changes in the rectus abdominis (RA) display an effect similar to those in paraspinal muscles with respect to the function of lower motor neurons in the thoracic spinal cord. The RA denervation was examined to determine its association with ventilation dysfunction in ALS. Methods: We collected the clinical data of 128 patients with sporadic ALS in Department of Neurology of Peking University Third Hospital from 2009 to 2013. EMG, Revised ALS Functional Rating Scale (ALSFRS-R) and forced vital capacity (FVC) were performed in all patients and the differences in the EMG changes in RA between those with and without FVC ≥ 80% were analysed. Results: The mean FVC value was 83.4% ± 17.1% (range: 45%–131%) of the predicted value. A total of 79 patients displayed FVC ≥80%, and 49 patients displayed FVC <80%. Compared with the patients displaying a normal FVC (60/79, 75.9%), spontaneous activity in RA was significantly different among those patients displaying an FVC <80% (47/49, 95.9%). In addition, spontaneous potentials in RA were more frequently detected in patients exhibiting dyspnea (32/33, 97.0%) than in patients without dyspnea (75/95, 78.9%). Conclusion: Spontaneous potentials in RA are associated with ventilation dysfunction and dyspnea in ALS patients. PMID:27569232

  18. Distribution and flux of /sup 226/Ra and /sup 228/Ra in the Amazon River estuary

    SciTech Connect

    Key, R.M.; Sarmiento, J.L.; Stallard, R.F.; Moore, W.S.

    1985-07-20

    Measurements of /sup 226/Ra and /sup 228/Ra in the Amazon River estuary show that desorption from riverborne suspended particulate matter in the estuary increases the riverine flux of both isotopes to the ocean by a factor of approximately 5 over the flux attributable to radium dissolved in the river water alone. The total Amazon flux supplies approximately 0.20% of the /sup 226/Ra and approximately 2.6% of the /sup 228/Ra standing crops in the near-surface Atlantic (0-200 m). Diffusive flux from estuarine and shelf sediments and desorption from resuspended sediments in the region of the estuary approximately double the estuarine /sup 226/Ra concentration and quadruple the estuarine /sup 228/Ra concentration above that caused by the dissolved and desorbed river components alone.

  19. Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA)

    PubMed Central

    Ribbens, C; Bonnet, V; Kaiser, M J; Andre, B; Kaye, O; Franchimont, N; De Groote, D; Beguin, Y; Malaise, M G

    2000-01-01

    Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1β, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen’s grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0·05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0·65, P = 0·0001) and sCD25 (r = 0·39, P = 0·0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest. PMID:10759783

  20. GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis.

    PubMed

    Li, Linbo; Wen, Wen; Jia, Rulin; Li, Yuhui; Liu, Xu; Sun, Xiaolin; Li, Zhanguo

    2016-09-01

    The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA. PMID:27098050

  1. Measurement of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs in foodstuffs samples collected from coastal areas of China.

    PubMed

    Tuo, Fei; Zhang, Qing; Zhou, Qiang; Xu, Cuihua; Zhang, Jing; Li, Wenhong; Zhang, Jianfeng; Su, Xu

    2016-05-01

    This study represents a total of 245 samples collected. The activities of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs were determined in samples of vegetables, tea, cereal (rice, wheat and corn), meat, poultry, freshwater product, seafood and seaweed that collected from the 30km safety zone of the Nuclear Power Plants (NPPs) area. All the samples radionuclide activities were quantified by using High Purity Germanium (HPGe) gamma spectrometry. The geometric mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.13, 0.16, 0.11, 68 and 0.02, respectively. The arithmetic mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.34, 0.65, 0.32, 111 and 0.09, respectively. Results of this study were compared with others, the measured values are the same with those of a previous investigation. Radiation doses due to the consumption of these foodstuffs to humans are estimated to comprise around 37-46% of the annual dose limit for public. PMID:26926376

  2. The Influence of Health Literacy and Patient Activation on Patient Information Seeking and Sharing.

    PubMed

    Ledford, Christy J W; Cafferty, Lauren A; Russell, Travis C

    2015-01-01

    This study provided an assessment of how patients looked for information to prepare for a clinical appointment and whether they shared those findings with their provider. A cross-sectional survey allowed insight into patient attitudes, motivations, and behavior in clinical real time. At two hospital-based clinics, 243 patients completed surveys before and after clinical appointments. Younger patients with higher communicative and critical health literacy prepared for clinical appointments with information searches. The predicted association of health literacy and patient activation with information sharing was not supported. This study shows that patients with higher patient activation perceived that their providers responded more positively to patient-obtained medical information. The role of critical health literacy may show that individuals choosing to seek information are considering not just their ability to conduct the search but also their ability to synthesize and critically analyze the results of the information search. An implication for providers is to become skilled in directly asking or passively surveying what outside information sources the patient has engaged with, no matter if the patient does or does not introduce the information. PMID:26513034

  3. Distribution of (223)Ra and (224)Ra in the Bo Sea embayment in Tianjin and its implication of submarine groundwater discharge.

    PubMed

    Liu, Lingling; Yi, Lixin; Cheng, Xiaoqing; Tang, Guoqiang

    2015-12-01

    Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. In this study, in order to analyze the distribution of naturally occurring short-lived radium isotopes and the relative SGD effect in Bo Sea embayment, (223)Ra and (224)Ra were measured in three parts of the embayment with the radium-delayed coincidence counting (RaDeCC) system. Subsequently, the mixing process was studied by the calculation of diffusion coefficients (Kx and Kz) and advection velocities (Vx and Vz) based on the 2D advection-diffusion model. Additionally, the apparent residence ages and SGD flux were quantified based on the (224)Ra and (223)Ra activities. The results showed that the Ra activities exponentially decreased with the distance offshore, and both the Kx and Vx took the order of northern part > southern part > middle part. In vertical direction, there was the maximum value of Vz and minimum Kz in middle part and the maximum Kz and minimum Vz in southern part. The average ages for the northern, middle and southern parts were 4.28, 7.38 and 3.73 days, respectively. The final SGD flux yielded by (224)Ra was 0.09, 0.01 and 0.03 m d(-1) in the northern, middle and southern parts, respectively. The SGD flux yielded by (223)Ra was 0.08, 0.01 and 0.03 m d(-1) in northern, middle and southern parts, respectively. The result indicates that there is the fastest exchange rate and the biggest SGD flux in the southern part in Bo Sea embayment. PMID:26318773

  4. Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Delongui, Francieli; Alfieri, Daniela Frizon; Lozovoy, Marcell Alysson Batisti; Amin, Ricardo Braga; Dichi, Isaias; Simão, Andréa Name Colado

    2016-01-01

    The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92. PMID:27340510

  5. Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

    PubMed Central

    Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

    2016-01-01

    The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA. PMID:27143816

  6. Cast adrift: Gortex cast liners allow greater patient activity.

    PubMed

    Dubowitz, Gerald; Miller, Deborah M

    2003-01-01

    Extremity fractures are a common injury, with nearly 1.5 million cases reported in the United States in 1998. Treatment often involves lengthy periods of immobilization. This report outlines the use of a Gortex cast liner by a subject who was able to engage in swimming and scuba diving during the healing process. We report that a Gortex cast liner may be considered for an active patient who is keen to return to limited activities during fracture healing. Apparently because of a lack of knowledge of their existence, physicians currently are underutilizing this method of casting in active patients. The use of Gortex liners elsewhere has been reported to have higher patient and physician satisfaction in both use and performance, with no reported detrimental effects on outcome. PMID:14518627

  7. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis

    PubMed Central

    Tchetverikov, I; Ronday, H; van El, B; Kiers, G; Verzijl, N; TeKoppele, J; Huizinga, T; DeGroot, J; Hanemaaijer, R

    2004-01-01

    Methods: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/α2-macroglobulin complexes, and collagen degradation products were measured by sandwich ELISA, activity assays, and HPLC in paired SF and serum samples from 15 patients with RA and 13 with OA. Results: MMPs were higher in SF of patients with RA than in OA or controls. MMP levels in SF of patients with OA were higher than in controls. In serum, levels of proMMP-3, -8 and -9 were higher in patients with RA than in OA or controls, whereas only proMMP-8 and -9 were higher in serum of patients with OA than in controls. A strong correlation was seen between serum and SF levels of MMP-8 and -9 in RA. Increased levels of MMP/α2-macroglobulin complexes indicated an MMP/TIMP imbalance in serum and SF in RA. SF hydroxyproline correlated significantly with SF levels of proMMP-9 in RA. Conclusions: Systemic MMP-8 and -9 levels represent the situation in the inflamed joint; MMP-9 is likely to be involved in degradation of joint collagen. The hypothesis of MMP/TIMP imbalance in RA is strengthened. PMID:15194590

  8. Demoralization, Patient Activation, and the Outcome of Spine Surgery.

    PubMed

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified "risk" factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial "maximizing" factors-characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients' strengths as well as their vulnerabilities. PMID:27417599

  9. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  10. Medical care costs of patients with rheumatoid arthritis during the prebiologics period in Japan: a large prospective observational cohort study.

    PubMed

    Tanaka, Eiichi; Inoue, Eisuke; Mannalithara, Ajitha; Bennett, Mihoko; Kamitsuji, Shigeo; Taniguchi, Atsuo; Momohara, Shigeki; Hara, Masako; Singh, Gurkirpal; Yamanaka, Hisashi

    2010-02-01

    Our objective was to describe outpatient medical care costs of patients with rheumatoid arthritis (RA) in the prebiologics period in Japan. The outpatient costs of 6,771 RA patients (17,666 patient years) who were enrolled in an observational cohort study at the Institute of Rheumatology, Rheumatoid Arthritis (IORRA), in Tokyo, Japan, were calculated from the billing records dated from 2000 to 2004. Associations between outpatient costs and variables such as age, RA duration, RA disease activities, and disability levels were assessed. The average outpatient cost gradually increased (+7.7% in 4 years) from 271,498 JPY per year in 2000 to 292,417 JPY per year in 2004. Medications accounted for approximately 50% of total outpatient costs, which increased 29.6% during the 4 years. The outpatient costs increased in association with aging, longer RA duration, higher Disease Activity Score of 28 Joints (DAS28), and higher Japanese version of Health Assessment Questionnaire (J-HAQ) score. Generalized linear regression analysis revealed that both DAS28 and J-HAQ scores were the most significant factors associated with outpatient costs (p < 0.001). Outpatient costs for patients with RA increased year after year over the 4-year period under observation in Japan. Medical costs were higher with increasing RA disease activity and disability levels. PMID:19821162

  11. Distribution of Active and Resting Periods in the Motor Activity of Patients with Depression and Schizophrenia

    PubMed Central

    Hauge, Erik; Berle, Jan Øystein; Dilsaver, Steven; Oedegaard, Ketil J.

    2016-01-01

    Objective Alterations of activity are prominent features of the major functional psychiatric disorders. Motor activity patterns are characterized by bursts of activity separated by periods with inactivity. The purpose of the present study has been to analyze such active and inactive periods in patients with depression and schizophrenia. Methods Actigraph registrations for 12 days from 24 patients with schizophrenia, 23 with depression and 29 healthy controls. Results Patients with schizophrenia and depression have distinctly different profiles with regard to the characterization and distribution of active and inactive periods. The mean duration of active periods is lowest in the depressed patients, and the duration of inactive periods is highest in the patients with schizophrenia. For active periods the cumulative probability distribution, using lengths from 1 to 35 min, follows a straight line on a log-log plot, suggestive of a power law function, and a similar relationship is found for inactive periods, using lengths from 1 to 20 min. For both active and inactive periods the scaling exponent is higher in the depressed compared to the schizophrenic patients. Conclusion The present findings add to previously published results, with other mathematical methods, suggesting there are important differences in control systems regulating motor behavior in these two major groups of psychiatric disorders. PMID:26766953

  12. Serum paraoxonase 1 activity in patients with iron deficiency anemia

    PubMed Central

    Gedikbasi, Asuman; Akalin, Nilgul; Gunaldi, Meral; Yilmaz, Deniz; Mert, Meral; Harmankaya, Ozlem; Soylu, Aliye; Karakaya, Pinar; Kumbasar, Abdulbaki

    2016-01-01

    Introduction In this study we aimed to detect paraoxonase 1 (PON-1) activity in iron deficiency anemia (IDA) and to compare it with healthy controls by observing the change after iron therapy. Material and methods In this study, 50 adult patients with IDA and 40 healthy subjects were enrolled. All patients were analyzed at the beginning and after treatment according to laboratory assessments. Results Mean paraoxonase and arylesterase activities in the iron deficiency anemia group were significantly lower than mean activities of the control group (102.4 ±19.2 U/l and 163.3 ±13.68 U/l, respectively and 157.3 ±26.4 U/l and 256.1 ±24.6 U/l, respectively; p = 0.0001 for both). Paraoxonase and arylesterase activities significantly increased after treatment for IDA (143.2 ±13.9 and 197.6 ±27.9 U/l, respectively, p = 0.0001). Mean activities after treatment with iron were significantly lower than mean activities in the control group (p = 0.002; p = 0.0001 respectively). Conclusions Paraoxonase and arylesterase activities in patients with IDA significantly increased after treatment with iron therapy. In adults IDA may also be one of the factors associated with increased risk of atherosclerosis. PMID:27478448

  13. Complement Activation in Trauma Patients Alters Platelet Function.

    PubMed

    Atefi, Gelareh; Aisiku, Omozuanvbo; Shapiro, Nathan; Hauser, Carl; Dalle Lucca, Jurandir; Flaumenhaft, Robert; Tsokos, George C

    2016-09-01

    Trauma remains the main cause of death for both civilians and those in uniform. Trauma-associated coagulopathy is a complex process involving inflammation, coagulation, and platelet dysfunction. It is unknown whether activation of complement, which occurs invariably in trauma patients, is involved in the expression of trauma-associated coagulopathy. We designed a prospective study in which we enrolled 40 trauma patients and 30 healthy donors upon arrival to the emergency department of BIDMC. Platelets from healthy individuals were incubated with sera from trauma patients and their responsiveness to a thrombin receptor-activating peptide was measured using aggregometry. Complement deposition on platelets from trauma patients was measured by flow cytometry. Normal platelets displayed hypoactivity after incubation with trauma sera even though exposure to trauma sera resulted in increased agonist-induced calcium flux. Depletion of complement from sera further blocked activation of hypoactive platelets. Conversely, complement activation increased aggregation of platelets. Platelets from trauma patients were found to have significantly higher amounts of C3a and C4d on their surface compared with platelets from controls. Depletion of complement (C4d, C3a) reversed the ability of trauma sera to augment agonist-induced calcium flux in donor platelets. Our data indicate that complement enhances platelet aggregation. Despite its complement content, trauma sera render platelets hypoactive and complement depletion further blocks activation of hypoactive platelets. The defect in platelet activation induced by trauma sera is distal to receptor activation since agonist-induced Ca2+ flux is elevated in the presence of trauma sera owing to complement deposition. PMID:27355402

  14. Immunoglobulin G and A Antibody Responses to Bacteroides forsythus and Prevotella intermedia in Sera and Synovial Fluids of Arthritis Patients

    PubMed Central

    Moen, Ketil; Brun, Johan G.; Madland, Tor Magne; Tynning, Turid; Jonsson, Roland

    2003-01-01

    compared to those in OA-SF samples. Significantly lower levels of IgG and IgA antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group. This indicates the presence of an active antibody response in synovial tissue and illustrates a potential connection between periodontal and joint diseases. PMID:14607865

  15. Does modafinil enhance activity of patients with myotonic dystrophy?

    PubMed Central

    Lammers, G.J.; van Dijk, J.G.

    2007-01-01

    We performed a double-blind placebo-controlled crossover study in 13 patients with myotonic dystrophy to address the question whether modafinil, known to improve hypersomnolence in myotonic dystrophy, may improve levels of activity as well. We used the Epworth Sleepiness Scale as a measure of hypersomnolence and a structured interview of the patient and the partner or housemate as a measure of activity. We additionally used a restricted form of the RAND-36 to relate a possible improvement of activity to perceived general health. We confirmed earlier positive findings of modafinil regarding reduced somnolence (p = 0.015), but no significant effects were seen regarding activity levels (p = 0.2 for patients’ self-reports and 0.5 for partners’ reports). PMID:17285226

  16. Non Activated Protein C Supplementation in Septic Pediatric Hematological Patients

    PubMed Central

    Perillo, Teresa; Muggeo, Paola; Arcamone, Giampaolo; Leonardis, Francesco De; Santoro, Nicola

    2016-01-01

    The purpose of the study was to examine safety and efficacy of non-activated Protein C (PC) supplementation in our cohort of septic pediatric hematological patients. We conducted a retrospective study of 22 septic patients receiving human plasma-derived PC concentrate from 2008 to 2015 at our Pediatric Oncology Center (Bari, Italy). The Surviving sepsis campaign definitions for sepsis, severe sepsis and septic shock were used to define the patients’ septic status. For each patient, we calculated Lansky performance status scale (LPSS) and a risk score defined the Hematologic risk score (HRS) that we created in 2007. Patients were defined as High risk for severe sepsis/septic shock in case of HRS>3. HRS<3 identified low risk patients. Baseline serum PC levels, PC administration dosage and duration and days until a 20% improvement in LPSS. Observed baseline serum PC levels (bPC) blood concentrations ranged from 31 to 80%. Patients received PC supplementation in case of low age-related bPC levels or >10% PC concentration decrease within 12 hours from the first evaluation. All patients received 80 U/kg/day PC, intravenously, every twenty-four hours. No drug-related adverse event was observed. The observed sepsis-related mortality rate in our cohort was 9%. PC supplementation in our cohort appeared to be safe, and, probably due to prompt PC administration, we observed an overall mortality that was much lower than expected mortality in cancer severe septic patients. PMID:27433305

  17. Tryptophan degradation increases with stage in patients with rheumatoid arthritis.

    PubMed

    Schroecksnadel, Katharina; Winkler, Christiana; Duftner, Christian; Wirleitner, Barbara; Schirmer, Michael; Fuchs, Dietmar

    2006-05-01

    Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The proinflammatory cytokine interferon-gamma in various cells, including monocytes, induces the enzyme indoleamine (2,3)-dioxygenase (IDO), which converts tryptophan to kynurenine. In sera of 22 patients (17 women and 5 men) with RA stages 1 to 4 according to Steinbrocker, the concentrations of tryptophan and kynurenine were measured by high-pressure liquid chromatography. To estimate IDO activity, the kynurenine to tryptophan ratio (kyn/trp) was calculated. In parallel, concentrations of the macrophage activation marker neopterin were determined by enzyme-linked immunosorbent assay. Tryptophan concentrations were lower in patients with RA, and the decrease in serum tryptophan correlated with increase in stage (p<0.05). Kyn/trp correlated well with neopterin concentrations, which were elevated in most patients. Whereas higher C-reactive protein concentrations and erythrocyte sedimentation rates were observed in patients with greater disease activity, tryptophan and neopterin concentrations did not differ between patients with different subjective disease activity graded by the physician. Deficiency of the essential amino acid tryptophan in patients with RA most likely results from immune activation involved in the pathogenesis of the disease. It could also be relevant for the mood of patients, as tryptophan is the precursor of serotonin. PMID:16261283

  18. Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice

    PubMed Central

    Bykerk, Vivian P; Östör, Andrew J K; Alvaro-Gracia, José; Pavelka, Karel; Ivorra, José Andrés Román; Graninger, Winfried; Bensen, William; Nurmohamed, Michael T; Krause, Andreas; Bernasconi, Corrado; Stancati, Andrea; Sibilia, Jean

    2012-01-01

    Objective To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). Methods Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. Results Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission. Conclusions In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns. PMID:22615456

  19. Disequilibrium between [sup 226]Ra and supported [sup 210]Pb in a sediment core from a shallow Florida lake

    SciTech Connect

    Brenner, M.; Peplov, A.J.; Schelske, C.L. )

    1994-07-01

    [sup 210]Pb dating can be used to assign ages in lake sediment cores, calculate rates of sediment accumulation, and determine the timing of recent changes in lake-watershed ecosystems. We used low-background gamma counting to measure [sup 226]Ra and total [sup 210]Pb activity in a core from Lake Rowell, Florida. [sup 226]Ra activity was high and strongly variable throughout the core, even exceeding total [sup 210]Pb activity in recently deposited sediments. We traced one source of Ra-rich sediments to the only inflow, Alligator Creek, where stream-bottom deposits display disequilibrium between [sup 226]Ra and supported [sup 210]Pb. High and variable [sup 226]Ra activity in the Lake Rowell profile argues for direct estimates of in situ Ra in lake sediment cores from disturbed watersheds that have Ra-bearing bedrock. Isotopic disequilibrium between [sup 226]Ra and supported [sup 210]Pb makes it difficult to distinguish between supported and unsupported [sup 210]Pb activity throughout the Lake Rowell core and would require special assumptions and nonconventional dating models to establish age-depth relationships. 78 refs., 3 figs., 1 tab.

  20. Demoralization, Patient Activation, and the Outcome of Spine Surgery

    PubMed Central

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified “risk” factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial “maximizing” factors—characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients’ strengths as well as their vulnerabilities. PMID:27417599

  1. U, Ra and Ba incorporation during precipitation of hydrothermal carbonates: Implications for {sup 226}Ra-Ba dating of impure travertines

    SciTech Connect

    Rihs, S.; Condomines, M.; Sigmarsson, O.

    2000-02-01

    The authors studied U, Ra and Ba incorporation in calcite in a natural CO{sub 2}-rich hydrothermal area from the French Massif Central. Along the western border of the Limagne graben, several springs are exploited for the petrification of various artifacts with calcite. These sites offer the opportunity to sample the water and the calcite layers downflow from the spring, and thus to follow the evolution of their U, Ra and Ba contents as precipitation proceeds. Results show that the apparent partition coefficients of U, Ra and Ba between water and calcite decrease during precipitation for the three elements. The authors found no direct relation between this variation and the main factors able to influence the partition coefficient, such as precipitation rate, which suggests that the incorporation of these trace elements could result from a composite process of adsorption and coprecipitation. Ra and Ba have a similar behavior, with an apparent partition coefficient decreasing from 0.80 to 0.47 for Ra and 0.96 to 0.68 for Ba, resulting in a small ({le}10%) variation of the Ra/Ba ratio. The apparent partition coefficient of U decreases from 0.38 to 0.20. These apparent coefficients are much higher than equilibrium values but might be applicable to natural systems with high precipitation rates. The authors also investigated the possibility of using the decay of the {sup 226}Ra-excess, or the decrease of the ({sup 226}Ra)/Ba ratio to date older deposits. Whereas the {sup 226}Ra initial activity at the time of deposition has not remained constant, and cannot be used for dating, the ({sup 226}Ra)/Ba method gives better results, when appropriate corrections for detrital contamination in Ba are made. Mixing diagrams using Th as an indicator of contamination allow calculation of the ({sup 226}Ra)/Ba ratio of the pure carbonate component. The calculated ages of five travertine layers range from 330 to 800 years, suggesting a mean deposition rate of about 1 cm/yr. The

  2. Motolimod effectively drives immune activation in advanced cancer patients

    PubMed Central

    Dietsch, Gregory N.

    2016-01-01

    ABSTRACT A novel approach to immunotherapy is the activation of toll-like receptor 8 (TLR8). Motolimod, a selective TLR8 agonist can act in concert with approved immunotherapies to sensitize T cells and augment natural killer (NK) cell function. Despite treatment with chemotherapeutic agents and advance disease, cancer patients remain sensitive to motolimod.

  3. Exercise in Treating Hypertension: Tailoring Therapies for Active Patients.

    ERIC Educational Resources Information Center

    Chintanadilok, Jirayos

    2002-01-01

    Exercise can be definitive therapy for some, and adjunctive therapy for many, people with hypertension, though people with secondary hypertension may not derive as much benefit. Low-to- moderate-intensity aerobic exercise can help with mild hypertension and reduce drug dosages in more severe cases. For active patients requiring medication,…

  4. Patient activation and advocacy: which literacy skills matter most?

    PubMed

    Martin, Laurie T; Schonlau, Matthias; Haas, Ann; Derose, Kathryn Pitkin; Rosenfeld, Lindsay; Buka, Stephen L; Rudd, Rima

    2011-01-01

    Attention to the effect of a patient's literacy skills on health care interactions is relatively new. So, too, are studies of either structural or personal factors that inhibit or support a patient's ability to navigate health services and systems and to advocate for their own needs within a service delivery system. Contributions of the structural environment, of interpersonal dynamics, and of a variety of psychological and sociological factors in the relationship between patients and providers have long been under study. Less frequently examined is the advocacy role expected of patients. However, the complex nature of health care in the United States increasingly requires a proactive stance. This study examined whether four literacy skills (reading, numeracy, speaking, and listening) were associated with patient self-advocacy--a component of health literacy itself--when faced with a hypothetical barrier to scheduling a medical appointment. Although all literacy skills were significantly associated with advocacy when examined in isolation, greater speaking and listening skills remained significantly associated with better patient advocacy when all four skills were examined simultaneously. These findings suggest that speaking and listening skills and support for such skills may be important factors to consider when developing patient activation and advocacy skills. PMID:21951251

  5. Cardiovascular Disease Risk amongst African Black Patients with Rheumatoid Arthritis: The Need for Population Specific Stratification

    PubMed Central

    Solomon, Ahmed; Tsang, Linda; Woodiwiss, Angela J.; Millen, Aletta M. E.; Norton, Gavin R.; Dessein, Patrick H.

    2014-01-01

    Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further, reported data on CVD and its risk factors derive mostly from data obtained in the developed world. An earlier epidemiological health transition is intrinsic to persons living in rural areas and those undergoing urbanization. It is therefore conceivable that optimal CVD risk stratification differs amongst patients with RA from developing populations compared to those from developed populations. Herein, we briefly describe current CVD and its risk factor profiles in the African black population at large. Against this background, we review reported data on CVD risk and its potential stratification amongst African black compared to white patients with RA. Routinely assessed traditional and nontraditional CVD risk factors were consistently and independently related to atherosclerosis in African white but not black patients with RA. Circulating concentrations of novel CVD risk biomarkers including interleukin-6 and interleukin-5 adipokines were mostly similarly associated with both endothelial activation and atherosclerosis amongst African black and white RA patients. PMID:25157371

  6. Effect of trimebutine on colonic myoelectrical activity in IBS patients.

    PubMed

    Frexinos, J; Fioramonti, J; Bueno, L

    1985-01-01

    The effect of trimebutine 100 mg i.v. and placebo on colonic myoelectrical activity was investigated in 10 patients with the irritable bowel syndrome (IBS) (5 constipated and 5 diarrhoeic), using an intraluminal probe supporting 8 groups of electrodes. At each site examined from transverse to sigmoid colon, the electromyograms exhibited two kinds of spike bursts: short spike bursts (SSB) localized at one electrode site and appearing rhythmically at 10.3/min, and long spike bursts (LSB), isolated or propagated orally or aborally. Computerized analysis of the duration of each kind of spike burst showed that, as compared to the control, trimebutine 100 mg, selectively inhibited by 43 to 73% the mean duration of LSB activity in the transverse, descending and sigmoid colon, from 0 to 30 min after administration. The inhibitory effect was similar in constipated and diarrhoeic patients. Placebo injection did not significantly affect (p greater than 0.05) the duration of LSB and SSB activity. Variance analysis indicated that the inhibitory effect of trimebutine was significantly greater (p less than 0.05) on LSB activity in the transverse than the descending colon, and that it was absent from the sigmoid colon. The results suggest that trimebutine selectively inhibits the propulsive activity of the proximal two thirds of the colon in IBS patients, and that this effect cannot entirely explain its therapeutic efficacy in IBS. PMID:3987797

  7. Brain activation induced by psychological stress in patients with schizophrenia.

    PubMed

    Castro, M N; Villarreal, M F; Bolotinsky, N; Papávero, E; Goldschmidt, M G; Costanzo, E Y; Drucaroff, L; Wainsztein, A; de Achával, D; Pahissa, J; Bär, K-J; Nemeroff, C B; Guinjoan, S M

    2015-10-01

    Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions. PMID:26190301

  8. Metrological Determination of Natural Radioactive Isotopes {sup 226}Ra, {sup 228}Ra and {sup 210}Pb by Means of Ge Detector

    SciTech Connect

    Almeida, Maria Candida M. de; Delgado, Jose U.; Poledna, Roberto; Oliveira, Estela Maria de; Silva, Ronaldo L. da

    2008-08-07

    A metrological method to determine the activity per mass unity (activity concentration) of {sup 226}Ra and {sup 210}Pb ({sup 238}U decay series) and {sup 228}Ra ({sup 232}Th series) by gamma-ray spectrometers based on hyper-pure coaxial germanium detector was developed. In the soil the {sup 22}Ra (half-life = 1600 years) exhibits the same level of radioactivity as {sup 238}U (half-life 4.5x10{sup 9} years) because of a natural phenomenon called secular equilibrium. {sup 226}Ra decays into {sup 222}Rn (half-life = 3.8 days), a radioactive inert gas. After several days, the {sup 222}Rn naturally decays to {sup 218}Po (half-life = 3 minutes), where finally {sup 210}Pb (half-life = 22 years) is produced. The metrological capability of high-resolution gamma-ray spectrometry for naturally occurring radionuclides at environmental levels is showed, with emphasis on the use of 2 mL standard sources volume in a glass ampoule. Source preparation and calibration procedures are described. Radionuclide standards in an activity range of 10 to 250 Bq/g were produced which can be applied in a variety of environmental sample analysis (water, plant material, sediment, etc.). Uncertainties for {sup 226}Ra and {sup 210}Pb around 3% (k = 1) were obtained.

  9. 226Ra in the western Indian Ocean

    NASA Astrophysics Data System (ADS)

    Chung, Y.

    1987-09-01

    226Ra profiles have been measured in the western Indian Ocean as part of the 1977-1978 Indian Ocean GEOSECS program. These profiles show a general increase in deep and bottom water Ra concentration from the Circumpolar region to the Arabian Sea. A deep Ra maximum which originates in the Arabian Sea and in the Somali basin at about 3000 m depth spreads southward into the Mascarene basin and remains discernible in the Madagascar and Crozet basins. In the western Indian Ocean, the cold Antarctic Bottom Water spreads northward under the possibly southward-flowing deep water, forming a clear benthic front along the Crozet basin across the Southwest Indian Ridge into the Madagascar and Mascarene basins. The Antarctic Bottom Water continues to spread farther north to the Somali basin through the Amirante Passage at 10°S as a western boundary current. The benthic front and other characteristic features in the western Indian Ocean are quite similar to those observed in the western Pacific where the benthic front as a distinctive feature was first described by Craig et al. [15]. Across the Mid-Indian Ridge toward the Ceylon abyssal plain near the triple junction, Ra profiles display a layered structure, reflecting the topographic effect of the mid-ocean ridge system on the mixing and circulation of the deep and bottom waters. Both Ra and Si show a deep maximum north of the Madagascar basin. Linear relationships between these two elements are observed in the deep and bottom water with slopes increasing northward. This suggests a preferential input of Ra over Si from the bottom sediments of the Arabian Sea and also from the flank sediments of the Somali basin.

  10. Assessment of the usefulness of skin autofluorescence as an indicator of disease activity and of the risk of developing diabetes in patients suffering from rheumatoid arthritis

    PubMed Central

    Jeka, Sławomir; Kolossa, Katarzyna; Wojciechowski, Rafał; Wilińska-Jankowska, Arnika; Waszczak, Marzena

    2015-01-01

    Objectives Diabetes develops much more often in patients suffering from rheumatoid arthritis (RA) than in healthy population. One of the parameters which allow to evaluate the risk of developing diabetes and cardiovascular diseases (CVD) is the level of advanced glycation end products (AGE) in the skin. In patients suffering from RA, an increase in AGE level may be also linked with the course of the underlying disease. The aim of the study was to evaluate the correlation between the AGE level and the course of RA as well as other risk factors for the development of diabetes and CVD. Material and methods The study included 148 patients divided into three groups: group I – patients with RA (n = 102, 79 F/23 M), group II – patients with RA and diabetes (n = 21, 14 F/7 M), group III – healthy individuals (n = 25, 16 F/9 M). Each patient underwent a skin autofluorescence signal (SAF) examination with an AGE Reader, which allows the assessment of AGE level, as well as being subjected to the laboratory tests panel. Additionally, patients from group I and II have had their DAS28 (ESR) indicator calculated. Results In groups I, II, and III, the respective mean SAF values, expressed in arbitrary units [au], were to 2.54, 2.74, and 1.96 au. Between-group differences in terms of mean SAF values were statistically significant (p < 0.05). Conclusions Significantly higher mean SAF values in groups I and II as compared to group III suggest that the increase in the AGE level in patients with RA is linked with the underlying disease and does not have to correspond with the real risk of diabetes and CVD. In conclusion, despite the known limitations of the technique, measuring AGE levels allows for closer monitoring of RA patients who are at a higher risk of developing diabetes.

  11. Discovery of radioactive decay of /sup 222/Ra and /sup 224/Ra by /sup 14/C emission

    SciTech Connect

    Price, P.B.; Stevenson, J.D.; Barwick, S.W.; Ravn, H.L.

    1985-01-28

    Using the ISOLDE on-line isotope separator at CERN to produce sources of /sup 221/Fr, /sup 221/Ra, /sup 222/Ra, /sup 223/Ra, and /sup 224/Ra, and using polycarbonate track-recording films sensitive to energetic carbon nuclei but not to alpha particles, we have discovered two new cases of the rare /sup 14/C decay mode: in /sup 222/Ra and /sup 224/Ra. Our results for branching ratios, B, relative to alpha decay are for /sup 221/Fr and /sup 221/Ra, B<4.4 x 10/sup -12/; for /sup 222/Ra, B = (3.7 +- 0.6) x 10/sup -10/; for /sup 223/Ra, B = (6.1 +- 1.0) x 10/sup -10/; for /sup 224/Ra, B = (4.3 +- 1.2) x 10/sup -11/. .AE

  12. Selecting patients with severe sepsis for drotrecogin alfa (activated) therapy.

    PubMed

    Sollet, Jean-Pierre; Garber, Gary E

    2002-12-01

    Selecting patients for drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) therapy outside of a clinical trial setting requires knowledge of the rationale that led the Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) investigators to select the various entry criteria for the trial. Enrollment criteria for the study included a known or suspected infection, presence of at least 3 systemic inflammatory response syndrome (SIRS) criteria, and dysfunction of > or =1 organ or system. The infection criteria used in PROWESS were designed to be straightforward and were based on common clinical and radiological data. Although previous definitions of sepsis required only 2 SIRS criteria, the PROWESS trial investigators required the presence of > or =3 SIRS criteria to improve the sensitivity and specificity of these criteria for the diagnosis of sepsis. Acute organ dysfunction, the diagnostic criterion for severe sepsis, was used to define the study population because it identifies patients at significant risk of death. Characteristics of drotrecogin alfa (activated)-treated patients, including infection, modified SIRS criteria, and organ dysfunction, were similar to those of the placebo group and the general sepsis population. Proper clinical judgment and use of the these inclusion criteria as a guide will help clinicians select and treat sepsis patients with drotrecogin alfa (activated). PMID:12521613

  13. Barriers associated with reduced physical activity in COPD patients*

    PubMed Central

    Amorim, Priscila Batista; Stelmach, Rafael; Carvalho, Celso Ricardo Fernandes; Fernandes, Frederico Leon Arrabal; Carvalho-Pinto, Regina Maria; Cukier, Alberto

    2014-01-01

    OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. PMID:25410838

  14. Functional Analysis of the Phycomyces carRA Gene Encoding the Enzymes Phytoene Synthase and Lycopene Cyclase

    PubMed Central

    Sanz, Catalina; Velayos, Antonio; Álvarez, María Isabel; Benito, Ernesto P.; Eslava, Arturo P.

    2011-01-01

    Phycomyces carRA gene encodes a protein with two domains. Domain R is characterized by red carR mutants that accumulate lycopene. Domain A is characterized by white carA mutants that do not accumulate significant amounts of carotenoids. The carRA-encoded protein was identified as the lycopene cyclase and phytoene synthase enzyme by sequence homology with other proteins. However, no direct data showing the function of this protein have been reported so far. Different Mucor circinelloides mutants altered at the phytoene synthase, the lycopene cyclase or both activities were transformed with the Phycomyces carRA gene. Fully transcribed carRA mRNA molecules were detected by Northern assays in the transformants and the correct processing of the carRA messenger was verified by RT-PCR. These results showed that Phycomyces carRA gene was correctly expressed in Mucor. Carotenoids analysis in these transformants showed the presence of ß-carotene, absent in the untransformed strains, providing functional evidence that the Phycomyces carRA gene complements the M. circinelloides mutations. Co-transformation of the carRA cDNA in E. coli with different combinations of the carotenoid structural genes from Erwinia uredovora was also performed. Newly formed carotenoids were accumulated showing that the Phycomyces CarRA protein does contain lycopene cyclase and phytoene synthase activities. The heterologous expression of the carRA gene and the functional complementation of the mentioned activities are not very efficient in E. coli. However, the simultaneous presence of both carRA and carB gene products from Phycomyces increases the efficiency of these enzymes, presumably due to an interaction mechanism. PMID:21858003

  15. Asymmetric pallidal neuronal activity in patients with cervical dystonia.

    PubMed

    Moll, Christian K E; Galindo-Leon, Edgar; Sharott, Andrew; Gulberti, Alessandro; Buhmann, Carsten; Koeppen, Johannes A; Biermann, Maxine; Bäumer, Tobias; Zittel, Simone; Westphal, Manfred; Gerloff, Christian; Hamel, Wolfgang; Münchau, Alexander; Engel, Andreas K

    2014-01-01

    The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe- and GPi-LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology. PMID:24574981

  16. Uranium series disequilibria in ground waters from a fractured bedrock aquifer (Morungaba Granitoids--Southern Brazil): implications to the hydrochemical behavior of dissolved U and Ra.

    PubMed

    Reyes, Erika; Marques, Leila S

    2008-10-01

    Activity concentrations of dissolved (234)U, (238)U, (226)Ra and (228)Ra were determined in ground waters from two deep wells drilled in Morungaba Granitoids (Southern Brazil). Sampling was done monthly for little longer than 1 year. Significant disequilibrium between (238)U, (234)U and (226)Ra were observed in all samples. The variation of (238)U and (234)U activity concentrations and (234)U/(238)U activity ratios is related to seasonal changes. Although the distance between the two wells is short (about 900 m), systematic differences of activity concentrations of U isotopes, as well as of (234)U/(238)U, (226)Ra/(234)U and (228)Ra/(226)Ra activity ratios were noticed, indicating distinct host rock-water interactions. Slightly acidic ground water percolation through heterogeneous host rock, associated with different recharge processes, may explain uranium and radium isotope behavior. PMID:18514535

  17. Basophil Activation Test with Food Additives in Chronic Urticaria Patients

    PubMed Central

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU. PMID:24527415

  18. Step activity monitoring in lumbar stenosis patients undergoing decompressive surgery

    PubMed Central

    Schubert, Tim; Winter, Corinna; Brandes, Mirko; Hackenberg, Lars; Wassmann, Hansdetlef; Liem, Dennis; Rosenbaum, Dieter; Bullmann, Viola

    2010-01-01

    Symptomatic degenerative central lumbar spinal stenosis (LSS) is a frequent indication for decompressive spinal surgery, to reduce spinal claudication. No data are as yet available on the effect of surgery on the level of activity measured with objective long-term monitoring. The aim of this prospective, controlled study was to objectively quantify the level of activity in central LSS patients before and after surgery, using a continuous measurement device. The objective data were correlated with subjective clinical results and the radiographic degree of stenosis. Forty-seven patients with central LSS and typical spinal claudication scheduled for surgery were included. The level of activity (number of gait cycles) was quantified for 7 consecutive days using the StepWatch Activity Monitor (SAM). Visual analogue scales (VAS) for back and leg pain, Oswestry disability index and Roland–Morris score were used to assess the patients’ clinical status. The patients were investigated before surgery and 3 and 12 months after surgery. In addition, the radiographic extent of central LSS was measured digitally on preoperative magnetic resonance imaging or computed tomography. The following results were found preoperatively: 3,578 gait cycles/day, VAS for back pain 5.7 and for leg pain 6.5. Three months after surgery, the patients showed improvement: 4,145 gait cycles/day, VAS for back pain 4.0 and for leg pain 3.0. Twelve months after surgery, the improvement continued: 4,335 gait cycles/day, VAS for back pain 4.1 and for leg pain 3.3. The clinical results and SAM results showed significant improvement when preoperative data were compared with data 3 and 12 months after surgery. The results 12 months after surgery did not differ significantly from those 3 months after surgery. The level of activity correlated significantly with the degree of leg pain. The mean cross-sectional area of the spinal canal at the central LSS was 94 mm2. The radiographic results did not

  19. A Study on Sorption of (226)Ra on Different Clay Matrices.

    PubMed

    Alhajji, E; Al-Masri, M S; Khalily, H; Naoum, B E; Khalil, H S; Nashawati, A

    2016-08-01

    The sorption of radium 226 ((226)Ra) on different clay materials (bentonite, illite and a mixture of bentonite-illite) was studied. Clay materials are used in the construction of disposal pits for technically enhanced naturally occurring radioactive materials (TENORM) wastes (i.e., contaminated soil and sludge) generated by the oil and gas industry operations. Experimental conditions (pH, clay materials quantity, and activity concentrations of (226)Ra) were changed in order to determine the optimal state for adsorption of (226)Ra. The results showed that the concentration of adsorbed (226)Ra on clay materials increased with time to reach an equilibrium state after approximately 5 h. More than 95 % of the radium was adsorbed. The mixture of bentonite-illite (1/9) exhibited the greatest adsorption of radium under all experimental conditions. PMID:27329110

  20. Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis.

    PubMed

    Boyden, Sean D; Hossain, Imtiyaz N; Wohlfahrt, Alyssa; Lee, Yvonne C

    2016-06-01

    Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered. PMID:27097817

  1. Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA.

    PubMed Central

    Dabrowski, M P; Stankiewicz, W; Płusa, T; Chciałowski, A; Szmigielski, S

    2001-01-01

    BACKGROUND: Human peripheral blood mononuclear cells (PBMC) left in microcultures for 24h without mitogen do not respond to subsequent stimulation with PHA. They regain reactivity if the native culture medium is absorbed with other party lymphocytes or partially replaced with the medium from a PHA-stimulated culture. The observations suggest that, during the incubation, some inhibitory agent had accumulated in the culture medium. AIM: The study was performed to determine the nature of the observed phenomenon in respect of the possible role of monocytes and their products IL-1 and IL-1 receptor antagonist (IL-1ra), and to test for immunodiagnostic purposes the significance of quantifying the lymphocyte response to delayed stimulation with PHA in patients suffering from inflammatory prosesses. METHODS: Lymphocyte response to delayed stimulation with PHA, calculated as the lymphocyte-monokine interaction (LM) index, was determined in the microcultures of PBMC isolated from the blood of healthy donors or of patients with acute tonsilitis. The values of LM indices were compared with the ratios of IL-1ra/IL-1beta concentration estimated by enzyme-linked immunosorbent assay method in the culture supernatants. The influences of exogenous IL-1beta, IL-1ra, anti-IL1ra antibodies and antibiotic cefaclor on the monokine concentrations and on the values of LM index were tested. RESULTS AND CONCLUSIONS: The results show that the level of lymphocyte response to delayed stimulation with PHA (LM index) is inversely proportional to the ratio of IL-1ra/IL-1beta concentration in the culture. The low LM values at high IL-1ra/IL-1beta ratios in PBMC cultures from healthy donors, reversed proportions found in patients' PBMC (acute tonsilitis), and the cefaclor-induced reduction of LM value with correlated increase of the IL-1ra/IL-1beta ratio suggest that the LM assay may prove to be useful for immunodiagnostic purposes. PMID:11545246

  2. Patient Participation and Physical Activity during Rehabilitation and Future Functional Outcomes in Patients following Hip Fracture

    PubMed Central

    Lenze, Eric J.; Munin, Michael C.; Harrison, Christopher C; Brach, Jennifer S

    2016-01-01

    Objective We examined the association between physical activity recorded by Actigraphy during therapy sessions (therapy) to therapist rated patient participation and self reported future functional outcomes. We hypothesized those participants who were more active during rehab would have higher participation scores and better functional outcomes following hip fracture compared to those who were less active. Design Longitudinal study with 3 and 6 month follow-up. Setting Participants were recruited from skilled nursing (SN) and inpatient rehabilitation (IR) facilities. Participants Participants included 18 community dwelling older adults admitted to SN or IR facilities after hip fracture. Participants were included if they were ≥ 60 years of age and ambulatory with or without assistance from a device or another person. Intervention Not Applicable Main Outcome Measure Physical activity was quantified during participants’ rehab using the Actigraph accelerometer worn consecutively over 5 days. The Pittsburgh Participation Rating Scale was used to quantify patient participation during their inpatient therapy sessions. Self reported functional outcomes were measured by the Hip Fracture Functional Recovery Scale (HFRS) at baseline, 3 and 6 months following fracture. Results Participants with higher Actigraphy counts during rehab were ranked by their therapists as having excellent participation compared to those who were less active. Participants who were more active reported better functional abilities at both 3 and 6 month time points and achieved 78% and 91% recovery of self reported pre-fracture function compared to those who were less active achieving 64% and 73% recovery. Conclusion Actigraphy provides an objective measure of physical activity exhibiting predictive validity for future functional outcomes and concurrent validity against patient participation in patients after hip fracture. PMID:19345777

  3. Rapid Method for Ra-226 and Ra-228 in Water Samples

    SciTech Connect

    Maxwell, Sherrod, L. III

    2006-02-10

    The measurement of radium isotopes in natural waters is important for oceanographic studies and for public health reasons. Ra-226 (1620 year half-life) is one of the most toxic of the long-lived alpha emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The analysis of radium-226 and radium-228 in natural waters can be tedious and time-consuming. Different sample preparation methods are often required to prepare Ra-226 and Ra-228 for separate analyses. A rapid method has been developed at the Savannah River Environmental Laboratory that effectively separates both Ra-226 and Ra-228 (via Ac-228) for assay. This method uses MnO{sub 2} Resin from Eichrom Technologies (Darien, IL, USA) to preconcentrate Ra-226 and Ra-228 rapidly from water samples, along with Ba-133 tracer. DGA Resin{reg_sign} (Eichrom) and Ln-Resin{reg_sign} (Eichrom) are employed in tandem to prepare Ra-226 for assay by alpha spectrometry and to determine Ra-228 via the measurement of Ac-228 by gas proportional counting. After preconcentration, the manganese dioxide is dissolved from the resin and passed through stacked Ln-Resin-DGA Resin cartridges that remove uranium and thorium interferences and retain Ac-228 on DGA Resin. The eluate that passed through this column is evaporated, redissolved in a lower acidity and passed through Ln-Resin again to further remove interferences before performing a barium sulfate microprecipitation. The Ac-228 is stripped from the resin, collected using cerium fluoride microprecipitation and counted by gas proportional counting. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  4. Comparative Analysis Of 226Ra Soil-To-Plant Transfer In Cabbage Grown In Various Regions

    NASA Astrophysics Data System (ADS)

    Madruga, M. J.; Carvalho, F. P.; Silva, L.; Gouveia, J.

    2008-08-01

    The transfer of 226Ra from soil to cabbage was compared amongst regions, namely the surroundings of Urgeiriça uranium milling tailings (GE), regions with past uranium mining activities (GN1), and regions with no uranium mining activities and no uranium deposits (GN2). Results show a slight increase of the concentration ratio values at low radium concentration in soils. Statistical analysis of the mean 226Ra activity concentrations in soil and cabbage for the three regions was carried out. The comparison of 226Ra activity concentrations in soils indicated no difference (p>0.05), between GE and GN2 and significant differences (p<0.05) between GE and GN1 and between GN1 and GN2. Similar statistical results were obtained for 226Ra activity concentrations in cabbage from the same regions. It was concluded that radium Concentration Ratio (CR) for cabbage grown in the region of the main uranium milling site (GE) is of the same order of magnitude of CR in cabagge grown in background regions (GN2). However, 226Ra CR was higher in cabagge from the region with past uranium mining activities (GN1).

  5. Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a prospective study aimed at identification of diagnostic and prognostic biomarkers as well as therapeutic targets

    PubMed Central

    de Launay, Daphne; van de Sande, Marleen GH; de Hair, Maria JH; Grabiec, Aleksander M; van de Sande, Gijs PM; Lehmann, K Aad; Wijbrandts, Carla A; van Baarsen, Lisa GM; Gerlag, Danielle M; Tak, Paul P; Reedquist, Kris A

    2012-01-01

    Objectives To investigate the expression and activation of mitogen-activated protein kinases in patients with early arthritis who are disease-modifying antirheumatic drug (DMARD) naïve. Methods A total of 50 patients with early arthritis who were DMARD naïve (disease duration <1 year) were prospectively followed and diagnosed at baseline and after 2 years for undifferentiated arthritis (UA), rheumatoid arthritis (RA) (1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria), or spondyloarthritis (SpA). Synovial biopsies obtained at baseline were examined for expression and phosphorylation of p38, extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) by immunohistochemistry and digital analysis. Synovial tissue mRNA expression was measured by quantitative PCR (qPCR). Results ERK and JNK activation was enhanced at inclusion in patients meeting RA criteria compared to other diagnoses. JNK activation was enhanced in patients diagnosed as having UA at baseline who eventually fulfilled 1987 ACR RA criteria compared to those who remained UA, and in patients with RA fulfilling 2010 ACR/EULAR criteria at baseline. ERK and JNK activation was enhanced in patients with RA developing progressive joint destruction. JNK activation in UA predicted 1987 ACR RA classification criteria fulfilment (R2=0.59, p=0.02) after follow-up, and disease progression in early arthritis (R2=0.16, p<0.05). Enhanced JNK activation in patients with persistent disease was associated with altered synovial expression of extracellular matrix components and CD44. Conclusions JNK activation is elevated in RA before 1987 ACR RA classification criteria are met and predicts development of erosive disease in early arthritis, suggesting JNK may represent an attractive target in treating RA early in the disease process. PMID:21953337

  6. Argonne-Utah studies of /sup 224/Ra endosteal surface dosimetry

    SciTech Connect

    Schlenker, R.A.; Smith, J.M.

    1984-01-01

    The activities of /sup 212/Pb relative to /sup 224/Ra and of /sup 222/Rn relative to /sup 226/Ra were measured in bone surface deposits 24 h after radium injection into beagles. The fractional retention of /sup 220/Rn atoms was measured in vitro with hydrated and dehydrated bone samples to determine the effect of water content on the escape of radon from bone surfaces. The experimental data suggest that substantial /sup 224/Ra daughter product disequilibrium exists in bone surface deposits. Estimates for the lower and upper limits on the fractional retention of /sup 220/Rn in vivo are 0.05 and 0.25, respectively. The average bone surface activity of /sup 212/Pb relative to /sup 224/Ra ranged from 0.34 to 0.71 for four dogs, with the majority of the values toward the low end of the range. Only a small portion of the deposited /sup 212/Pb came from lead in the injection solution despite near equilibrium between /sup 224/Ra and its daughters at the time of injection. The retention data indicate that the endosteal tissue dose rate in the dogs at one day was actually one-third to about one-half that which would be calculated assuming equilibrium of /sup 224/Ra daughter products in bone surface deposits. 11 references, 2 figures, 7 tables.

  7. Sexual Activity and Heart Patients: A Contemporary Perspective.

    PubMed

    Stein, Ricardo; Sardinha, Aline; Araújo, Claudio Gil S

    2016-04-01

    Sexual activity (SA) encompasses several behaviors such as kissing (Ki), touching (T), oral (O) stimulation, masturbation (M), and vaginal/anal intercourse (I). The acronym KiTOMI is proposed here to represent these behaviors. SA, particularly coitus, is a major aspect of health-related quality of life and is often considered the most pleasant and rewarding exercise performed during an entire lifetime. Although several studies have been conducted on sexuality, relatively limited information is available regarding SA in patients with heart disease. Moreover, the level of evidence of this limited information is nearly always B or C. This article provides a comprehensive and updated review of the relevant literature and offers evidence and expert-based practical messages regarding SA in patients with heart disease. Considering the rationale for exercise prescription, SA is typically well tolerated by most clinically stable patients with heart disease. Even in more debilitated and sicker individuals, KiT activities would most likely be feasible and desirable. The absolute risk of major adverse cardiovascular events during SA is typically very low. Even lower death rates have been reported for specific groups, such as women in general, aerobically fit men, and asymptomatic young adults with congenital heart disease. Finally, we emphasize the relevance of sexual counselling for patients and their partners, including the proper use of medications to treat erectile dysfunction. Counselled patients will be reassured and adequately informed regarding how to gradually resume habitual SA after a major cardiac event or procedure, starting with KiT and progressively advancing to KiTOM until all KiTOMI activities are allowed. PMID:26690295

  8. The Effect of a Patient Portal With Electronic Messaging on Patient Activation Among Chronically Ill Patients: Controlled Before-and-After Study

    PubMed Central

    Linna, Miika; Rönkkö, Ilona

    2014-01-01

    Background It has been suggested that providing patients with access to their medical records and secure messaging with health care professionals improves health outcomes in chronic care by encouraging and activating patients to manage their own condition. Objectives The aim was to evaluate the effect of access to a patient portal on patient activation among chronically ill patients. Further, the relationship between temporal proximity of a severe diagnosis and patient activation were assessed. Methods A total of 876 chronically ill patients from public primary care were allocated to either an intervention group receiving immediate access to a patient portal that included their medical records, care plan, and secure messaging with a care team, or to a control group receiving usual care. Patient Activation Measure (PAM) at baseline and at 6-month follow-up was obtained from 80 patients in the intervention group and 57 patients in the control group; thus, a total of 137 patients were included in the final analysis. Results No significant effect of access to patient portal on patient activation was detected in this study (F 1,133=1.87, P=.17, η2=0.01). Patients starting at a lower level of activation demonstrated greater positive change in activation compared to patients starting at higher levels of activation in both the intervention and control groups. Further, patients diagnosed with a severe diagnosis during the intervention showed greater positive change in patient activation compared to patients whose last severe diagnosis was made more than 2 years ago. The results also suggest that the intervention had greatest effect on patients starting at the highest level of patient activation (difference in change of patient activation=4.82, P=.13), and among patients diagnosed within a year of the intervention (difference in change of patient activation=7.65, P=.12). Conclusions Time since last severe diagnosis and patient activation at baseline may affect changes in

  9. ZebRA: An overview of retinoic acid signaling during zebrafish development.

    PubMed

    Samarut, Eric; Fraher, Daniel; Laudet, Vincent; Gibert, Yann

    2015-02-01

    Retinoic acid (RA), the main active vitamin A derivative, is crucial for embryo development, regulating cellular processes, embryo patterning and organogenesis. Many studies performed in mammalian or avian models have successfully undertaken the investigation of the role played by RA during embryogenesis. Since the early 1980s, the zebrafish (Danio rerio) has emerged as a powerful developmental model to study the in vivo role of RA during embryogenesis. Unlike mammalian models, zebrafish embryogenesis is external, not only allowing the observation of the translucent embryo from the earliest steps but also providing an easily accessible system for pharmacological treatment or genetic approaches. Therefore, zebrafish research largely participates in deciphering the role of RA during development. This review aims at illustrating different concepts of RA signaling based on the research performed on zebrafish. Indeed, RA action relies on a multitude of cross-talk with other signaling pathways and requires a coordinated, dynamic and fine-regulation of its level and activity in both temporal and spatial dimensions. This review also highlights major advances that have been discovered using zebrafish such as the observation of the RA gradient in vivo for the first time, the effects of RA signaling in brain patterning, its role in establishing left-right asymmetry and its effects on the development of a variety of organs and tissues including the heart, blood, bone and fat. This review demonstrates that the zebrafish is a convenient and powerful model to study retinoic acid signaling during vertebrate embryogenesis. This article is part of a Special Issue entitled: Nuclear receptors in animal development. PMID:24928143

  10. Evaluation of macrophage antiviral activity in patients affected by neoplasia.

    PubMed

    Merendino, R A; Iannello, D; Arena, A; Bonina, L; Greco, V; Mesiti, M; Chillemi, S; Mastroeni, P

    1988-01-01

    The intrinsic antiviral activity of macrophages has been studied in healthy donors and in patients affected by breast cancer and melanoma. In vitro differentiated macrophages from blood-derived monocytes were infected with measles virus, herpes simplex virus type 2 and adenovirus 17. The challenge was carried out with different multiplicities of infection and the synthesis of virus was tested by evaluating the single cycle growth curve in 24 h. The results obtained show that the restriction of virus infectivity by macrophages is strongly influenced by the multiplicity of infection. This was particularly evident with the adenovirus 17. Moreover, macrophages from patients with melanoma and breast cancer showed an impairment of the intrinsic antiviral activity in comparison with normal subjects. PMID:2842553

  11. Paraoxonase Activity and Oxidative Status in Patients with Tinnitus

    PubMed Central

    Akyüz, Servet; Somuk, Battal Tahsin; Soyalic, Harun; Yılmaz, Beyhan; Taskin, Abdullah; Bilinc, Hasan; Aksoy, Nurten

    2016-01-01

    Background and Objectives The aim of this study was to investigate serum paraoxanase-1 (PON) activity, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) in tinnitus; and to compare the results with data from healthy subjects. Subjects and Methods A total of 114 subjects-54 patients with tinnitus and 60 healthy controls were enrolled in this study. Serum PON activity, TOS, TAS, and OSI levels were measured. Results In the tinnitus group, TAS, and PON were significantly lower than in the control group (p<0.001). However, the TOS, and OSI levels were significantly higher in the tinnitus group than in the control group (p<0.001). Conclusions According to the data obtained from the present study, patients with tinnitus were exposed to potent oxidative stress. Oxidative stress may be the key contributing factor to the pathogenesis of tinnitus. PMID:27144229

  12. Elevated soluble CD8 in the synovial fluid from patients with rheumatoid arthritis.

    PubMed

    Carpenter, A B; Eisenbeis, C H; Carrabis, S; Brown, M C; Ip, S H

    1990-01-01

    Suppressor/cytotoxic T cells express the surface marker CD8, which can be measured in a soluble form in culture supernatants of activated human lymphocytes. Using a sandwich immunoassay, we assessed the levels of soluble CD8 (sCD8) in serum from patients with rheumatoid arthritis (RA; n = 82), patients with degenerative joint disease (DJD; n = 40), and healthy controls. There were no differences in serum sCD8 levels among these groups. In contrast, the levels of soluble CD8 in the synovial fluid (SF) from patients with RA (n = 53) were significantly increased compared with the levels in 23 samples from patients with DJD (821 +/- 110 U/ml versus 213 +/- 13 U/ml, p less than 0.001). Synovial fluid sCD8 levels in the RA group were strikingly elevated, to a maximum value of 5,026 U/ml. In the majority of RA SF specimens (39 of 53), the values were significantly higher in the SF than the serum. Although the RA group had higher values of sCD8, such values were not significantly correlated with measured laboratory or clinical parameters. Current clinical and laboratory methods of evaluating patients may not be adequate in dealing with the complexity and heterogeneity of RA. Soluble CD8 values may be useful in further grouping patients with this disease. PMID:2121924

  13. Factors affecting daily activities of patients with cerebral infarction

    PubMed Central

    Liu, Peng; Zhou, Cheng-ye; Zhang, Ying; Wang, Yun-feng; Zou, Chang-lin

    2010-01-01

    BACKGROUND: Stroke is the leading cause of death and long-term disability. This study was undertaken to investigate the factors influencing daily activities of patients with cerebral infarction so as to take interventional measures earlier to improve their daily activities. METHODS: A total of 149 patients with first-episode cerebral infarction were recruited into this prospective study. They were admitted to the Encephalopathy Center, Department of Neurology, the First Affiliated Hospital of Wenzhou Medical College in Zhejiang Province from August 2008 to December 2008. The baseline characteristics of the patients and cerebral infarction risk factors on the first day of admission were recorded. White blood cell (WBC) count, plasma glucose (PG), and many others of laboratory targets were collected in the next morning. Barthel index (BI) was calculated at 2 weeks and 3 months respectively after onset of the disease at the outpatient clinic or by telephone call. Lung infection, urinary tract infection and atrial fibrillation if any were recorded on admission. The National Institute of Health Stroke Scale (NIHSS) scores and the GCS scores were recorded within 24 hours on and after admission, at the second week, and at the third month after the onset of cerebral infarction respectively. RESULTS: The factors of BI at 2 weeks and 3 months after onset were the initial PG level, WBC count and initial NIHSS scores. Besides, urinary tract infection on admission was also the factor for BI at 3 months. CONCLUSION: Active measures should be taken to control these factors to improve the daily activities of patients with cerebral infarction. PMID:25214953

  14. Simultaneous determination of 226Ra, 233U and 237Np by liquid scintillation spectrometry.

    PubMed

    Nebelung, Cordula; Baraniak, Lutz

    2007-02-01

    A method has been developed for the simultaneous determination of 226Ra, 233U and 237Np by liquid-scintillation (LS) spectrometry. This method consists of the evaluation of the alpha-spectrum that is composed of the strongly overlapping peaks of 226Ra, 233U, 237Np, 222Rn and 218Po in the energy range of 4.60-6.00 MeV and the single 214Po peak at 7.69 MeV. The alpha-peaks are analysed by a special peak fit function that considers the deviation of the alpha-peak at the low energy side from the pure Gaussian shape. First 237Np is determined using its daughter 233Pa by analysing the beta-spectrum in the range 150-570 keV. 226Ra follows from the alpha-spectrum that is measured 6 weeks after sample preparation, i.e., 226Ra is determined from the radioactive equilibrium with its short-lived daughters 222Rn, 218Po and 214Po. Finally the 233U activity results from the fitted spectrum in the range of 4.4-4.8 MeV by subtracting the activity of 226Ra and 237Np. Knowing the exact energy position of the LS-peaks an alternative evaluation consists in the accurate deconvolution of the first three peaks that are formed by 226Ra and 233U (maximum of both at channel 700), 237Np (maxima at channels 700 and 725) and 222Rn (maximum at channel 737). In these two ways 226Ra, 233U and 237Np can be determined in mutual activity ratios of 1:50 with a relative standard deviation of less than 4% for the major activity and 9% for the minor activity. PMID:17142052

  15. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use

    PubMed Central

    Hazes, Johanna M.W.; Coulie, Pierre G.; Geenen, Vincent; Vermeire, Séverine; Carbonnel, Franck; Louis, Edouard; Masson, Pierre

    2011-01-01

    It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant. PMID:21890617

  16. Prevalence of atherosclerosis in patients with inactive rheumatoid arthritis.

    PubMed

    Dehghan, Pooneh; Rajaei, Alireza; Moeineddin, Reza; Alizadeh, Afshin Mohammad

    2015-08-01

    Patients with rheumatoid arthritis (RA) exhibit higher cardiovascular morbidity and mortality than the general population. The common carotid artery intima-media thickness (CCA-IMT) measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in patients with inactive RA. CCA-IMT was measured at the level of the carotid bifurcation in 35 patients with RA and 35 age- and sex-matched controls. CCA-IMT measurements more than two standard deviations above the mean measurement of the control group were defined as abnormal. Patients and controls with known cardiovascular risk factors were excluded from the study. The following data were taken into consideration for each patient: age, sex, duration of RA, and medication received by the patient. These variables were adjusted in data analysis. The patients were required to have had normal C-reactive protein levels for at least 1 year and no clinical signs or symptoms of active disease. An independent t test and chi-squared test were used for statistical analysis. Nine patients with RA (25.7 %) and two controls (5.7 %) had an abnormal IMT. Patients showed more carotid atherosclerotic plaques and a higher mean CCA-IMT than did controls (48.6 vs. 14.3 % and 0.705 ± 0.140 vs. 0.580 ± 0.125, respectively). An abnormal CCA-IMT was more prevalent in patients >50 years of age with >5 years of involvement (P = 0.001). These results support the theory that chronic inflammation in patients with inactive RA is associated with atherosclerosis and suggest the use of carotid ultrasonography as a useful tool with which to establish the risk of cardiovascular disease. PMID:26122966

  17. Evaluation of 224Ra as a tracer for submarine groundwater discharge in Long Island Sound (NY)

    NASA Astrophysics Data System (ADS)

    Garcia-Orellana, J.; Cochran, J. K.; Bokuniewicz, H.; Daniel, J. W. R.; Rodellas, V.; Heilbrun, C.

    2014-09-01

    The approach to quantify submarine groundwater discharge using Ra isotopes generally involves developing a Ra mass balance in an estuary, bay or lagoon. In this work we present a 224Ra mass balance used to evaluate the importance of the submarine groundwater discharge (SGD) in Long Island Sound (NY, US), the third most important estuary in US, located between Long Island and Connecticut that is usually affected by summertime hypoxia in the western basin. Three surveys were conducted between April 2009 and August 2010 where 25 water stations were sampled for Ra isotopes, oxygen and Mn. Stations were oriented along 4 transects: one axial extending from the western to the eastern Sound and three longitudinal transects in the western, central and eastern Sound. The inventory of 224Ra in the water column in summer was circa 2 times greater than in winter, suggesting an increased 224Ra flux to the Sound in summer. A mass balance for 224Ra was constructed considering tidal exchange, inputs from rivers, desorption from resuspended particles, diffusive fluxes (including bioirrigation) from bottom sediments and radioactive decay in the water column. Fluxes of 224Ra from bottom sediments were measured by incubating cores under oxic conditions in a continuous flow mode such that the overlying water was circulated through a Mn-oxide fiber to maintain a constant activity of 224Ra. Fluxes from muddy sediments (comprising ∼67% of the Sound bottom) ranged from 127 to 312 dpm m-2 d-1 and were ∼60 dpm m-2 d-1 in sandy sediments (33% of the Sound). Incubations under hypoxic conditions showed variable fluxes depending on reduction and mobilization of Mn. The 224Ra mass balance shows a net input of Ra to the Sound of 106 ± 50 × 1012 dpm y-1 in spring and 244 ± 112 × 1012 dpm y-1 in the summer that is attributed to SGD. Elevated 224Ra values were observed near shore and in the pore fluids of the coarse beach sands along the Long Island and Connecticut coasts, suggesting that SGD

  18. 226Ra or 226Ra/Ba dating of Holocene volcanic rocks: application to Mt. Etna and Merapi volcanoes

    NASA Astrophysics Data System (ADS)

    Condomines, M.; Gauthier, P. J.; Tanguy, J. C.; Gertisser, R.; Thouret, J. C.; Berthommier, P.; Camus, G.

    2005-02-01

    This paper shows how 226Ra- 230Th disequilibria can be used to date Holocene volcanic rocks from some well selected volcanoes. A systematic study of these disequilibria on historical or well-dated volcanic samples is indeed first required to test the applicability of this method. Two examples are described here to illustrate its potential. In the case of Mt. Etna, the good correlation observed between ( 226Ra) 0 activities at the time of eruption and Th contents in lava flows from the last two millennia [M. Condomines, J.C. Tanguy, V. Michaud, Magma dynamics at Mt. Etna: constraints from U-Th-Ra-Pb radioactive disequilibria and Sr isotopes in historical lavas, Earth Planet. Sci. Lett. 132 (1995) 25-41] is used to infer the ages of several newly analysed lava flows. The calculated ages are in good agreement with those deduced from the archaeomagnetic curve describing the variation of the geomagnetic field direction in southern Italy [J.C. Tanguy, I. Bucur, J.F.C. Thompson, Geomagnetic secular variation in Sicily and revised ages of historic lavas from Mt. Etna, Nature 318 (1985) 453-455, J.C. Tanguy, M. Le Goff, V. Chillemi, A. Paiotti, C. Principe, S. La Delfa, G. Patane, Variation séculaire de la direction du champ géomagnétique enregistrée par les laves de l'Etna et du Vésuve pendant les deux derniers millénaires, C. R. Acad. Sci. Paris 329 (1999) 557-564, J.C. Tanguy, M. Le Goff, C. Principe, S. Arrighi, V. Chillemi, A. Paiotti, S. La Delfa, G. Patane, Archaeomagnetic dating of Mediterranean volcanics of the last 2100 years: validity and limits. Earth Planet. Sci. Lett. 211 (2003) 111-124]. We also present a whole set of new U-series data on historical, recent, and older samples from Merapi (Indonesia), and show that the ( 226Ra)/Ba ratio has probably maintained a quasi-steady state value during at least the past four millennia, and can be used to infer the ( 226Ra) 0/Ba ratio of old volcanics at the time of eruption, and thus their ages. Comparison with

  19. Etanercept: therapeutic use in patients with rheumatoid arthritis

    PubMed Central

    Garrison, L.; McDonnell, N.

    1999-01-01

    Tumour necrosis factor (TNF) plays a central part in the pathophysiology of rheumatoid arthritis (RA). TNF initiates signal transduction by interacting with surface bound TNF receptors. Soluble tumour necrosis factor receptors (sTNFRs) act as natural inhibitors of TNF activity. Etanercept, recombinant p75 sTNFR:Fc fusion protein, has received approval from the US Food and Drug Administration for patients with RA and juvenile RA (JRA) who have failed treatment with at least one other drug. Etanercept has demonstrated excellent safety and efficacy in large scale, randomised, double blind, placebo controlled trials of patients with RA and JRA who are refractory to other disease modifying anti-rheumatic drugs. The therapeutic effects mediated by etanercept are rapid and sustained. Combining etanercept with methotrexate was found to be safe and more effective than treatment with methotrexate alone in the treatment of RA. These clinical findings demonstrate that etanercept can result in symptomatic improvement in patients with RA and JRA. Etanercept is an important new addition to the treatment of these diseases.

 PMID:10577976

  20. Health Literacy and Education as Mediators of Racial Disparities in Patient Activation Within an Elderly Patient Cohort.

    PubMed

    Eneanya, Nwamaka D; Winter, Michael; Cabral, Howard; Waite, Katherine; Henault, Lori; Bickmore, Timothy; Hanchate, Amresh; Wolf, Michael; Paasche-Orlow, Michael K

    2016-01-01

    The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement. PMID:27524777

  1. Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor α.

    PubMed

    Mainz, Emilie R; Serafin, D Stephen; Nguyen, Tuong T; Tarrant, Teresa K; Sims, Christopher E; Allbritton, Nancy L

    2016-08-01

    The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFα treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest. PMID:27391352

  2. Type I collagen degradation does not diminish with RA disease duration

    PubMed Central

    Hakala, M; Aho, K; Aman, S; Luukkainen, R; Kauppi, M; Risteli, J

    2001-01-01

    OBJECTIVE—To assess the relation between type I collagen degradation and the duration of rheumatoid arthritis (RA).
METHODS—The serum concentrations of cross linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in a community based series (90 patients) and a hospital based series (59 patients) were re-evaluated with reference to the duration of RA.
RESULTS—The serum ICTP showed a positive correlation with the duration of the disease in the hospital based series (rs=0.40, p<0.01) but not in the community based one (rs=0.18, p=0.10).
CONCLUSIONS—Type I collagen degradation predominantly reflecting pathological bone destruction does not seem to diminish in longlasting RA.

 PMID:11247878

  3. Geometric complexity identifies platelet activation in familial hypercholesterolemic patients.

    PubMed

    Bianciardi, Giorgio; Aglianò, Margherita; Volpi, Nila; Stefanutti, Claudia

    2015-06-01

    Familial hypercholesterolemia (FH), a genetic disease, is associated with a severe incidence of athero-thrombotic events, related, also, to platelet hyperreactivity. A plethora of methods have been proposed to identify those activated circulating platelets, none of these has proved really effective. We need efficient methods to identify the circulating platelet status in order to follow the patients after therapeutic procedures. We propose the use of computerized fractal analysis for an objective characterization of the complexity of circulating platelet shapes observed by means of transmission electron microscopy in order to characterize the in vivo hyperactivated platelets of familial hypercholesterolemic patients, distinguishing them from the in vivo resting platelets of healthy individuals. Platelet boundaries were extracted by means of automatically image analysis. Geometric complexity (fractal dimension, D) by box counting was automatically calculated. The platelet boundary observed by electron microscopy is fractal, the shape of the circulating platelets is more complex in FH (n = 6) than healthy subjects (n = 5, P < 0.01), with 100% correct classification in selected individuals. In vitro activated platelets from healthy subjects show an analogous increase of D. The observed high D in the platelet boundary in FH originates from the in vivo platelet activation. Computerized fractal analysis of platelet shape observed by transmission electron microscopy can provide accurate, quantitative data to study platelet activation in familial hypercholesterolemia and after administration of drugs or other therapeutic procedures. PMID:25877374

  4. Resting state activity in patients with disorders of consciousness.

    PubMed

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Mélanie, Boly; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    2011-01-01

    Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients' active collaboration in data acquisition. PMID:21693087

  5. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  6. Low prevalence of Blastocystis sp. in active ulcerative colitis patients.

    PubMed

    Rossen, N G; Bart, A; Verhaar, N; van Nood, E; Kootte, R; de Groot, P F; D'Haens, G R; Ponsioen, C Y; van Gool, T

    2015-05-01

    Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls. PMID:25680316

  7. 226Ra bioavailability to plants at the Urgeiriça uranium mill tailings site.

    PubMed

    Madruga, M J; Brogueira, A; Alberto, G; Cardoso, F

    2001-01-01

    Large amounts of solid wastes (tailings) resulting from the exploitation and treatment of uranium ore at the Urgeiriça mine (north of Portugal) have been accumulated in dams (tailing ponds). To reduce the dispersion of natural radionuclides into the environment, some dams were revegetated with eucalyptus (Eucalyptus globolus) and pines (Pinus pinea). Besides these plants, some shrubs (Cytisus spp.) are growing in some of the dams. The objective of this study is to determine the 226Ra bioavailability from uranium mill tailings by quantifying the total and available fraction of radium in the tailings and to estimate its transfer to plants growing on the tailing piles. Plant and tailing samples were randomly collected and the activity concentration of 226Ra in plants (aerial part and roots) and tailings was measured by gamma-spectrometry. The exchangeable fraction of radium in tailings was quantified using one single step extraction with 1 mol dm-3 ammonium acetate (pH = 7) or 1 mol dm-3 calcium chloride solutions. The results obtained for 226Ra uptake by plants show that 226Ra concentration ratios for eucalyptus and pines decrease at low 226Ra concentrations in the tailings and appear relatively constant at higher radium concentrations. For shrubs, the concentration ratios increase at higher 226Ra solid waste concentrations approaching a saturation value. Percentage values of 16.0 +/- 8.3 and 12.9 +/- 8.9, for the fraction of radium extracted from the tailings, using 1 mol dm-3 ammonium acetate or calcium chloride solutions, respectively, were obtained. The 226Ra concentration ratios determined on the basis of exchangeable radium are one order of magnitude higher than those based on total radium. It can be concluded that, at a 95% confidence level, more consistent 226Ra concentration ratios were obtained when calculated on the basis of available radium than when total radium was considered, for all the dams. PMID:11379070

  8. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation

    PubMed Central

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-01-01

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. PMID:26592552

  9. Evidence for altered opioid activity in patients with cancer.

    PubMed Central

    Lissoni, P.; Barni, S.; Paolorossi, F.; Crispino, S.; Rovelli, F.; Ferri, L.; Delitala, G.; Tancini, G.

    1987-01-01

    Endogenous opioid peptides have been shown to be involved in the regulation of tumour growth. At present, however, no data are available about the secretion of opioid peptides in cancer patients. To draw some preliminary conclusions on opioid brain function in human neoplasms, we evaluated hypophyseal hormone responses to the administration of a met-enkephalin analogue, FK 33-824. The study included 14 patients affected by early or advanced neoplastic disease, 12 healthy subjects and 7 patients with a chronic medical illness other than cancer. FK 33-824 was given intravenously at a dose of 0.3 mg. Venous blood samples were collected at zero time, and 30, 60 and 120 min after drug administration. In each sample, PRL, GH, LH, cortisol and beta-endorphin levels were measured by RIA. In all normal subjects and in patients with non-neoplastic chronic illness, FK 33-824 induced a rise in PRL and GH levels, and a decrease in LH, cortisol and beta-endorphin. A normal endocrine response to FK 33-824 was seen in our cancer patient only, while in the other cases with tumour no hormonal changes or a paradoxical response were seen after FK 33-824. Based on the fact that an abnormal endocrine response to FK 33-824 has been described in hypothalamic-pituitary disorders, in which anomalous brain opioid activity has been demonstrated, these results suggest the existence of an altered function of the opioid system in cancer patients, the clinical importance of which remains to be determined. PMID:2963662

  10. Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis

    PubMed Central

    Stremmel, W; Merle, U; Zahn, A; Autschbach, F; Hinz, U; Ehehalt, R

    2005-01-01

    Background and aims: We examined the hypothesis of an anti-inflammatory effect of phosphatidylcholine in ulcerative colitis. Methods: A phase IIA, double blind, randomised, placebo controlled study was performed in 60 patients with chronic active, non steroid dependent, ulcerative colitis, with a clinical activity index (CAI) of ⩾4. Retarded release phosphatidylcholine rich phospholipids and placebo were administered at a dose of 6 g daily over three months. The primary end point was a change in CAI towards clinical remission (CAI ⩽3) or CAI improvement by ⩾50%. Secondary end points included ⩾50% changes in endoscopic activity index (EAI), histology, and quality of life scores. Results: Induction of clinical remission (CAI ⩽3) as the primary outcome variable was attained by 16 (53%) patients in the phosphatidylcholine treated group compared with three (10%) in the placebo group (p<0.00001). The rate of clinical remission and CAI improvement was 90% in the phosphatidylcholine group and only 10% in the placebo group. A median drop of seven points in the CAI score (70% improvement) was recorded in the phosphatidylcholine group compared with no change in the placebo group. Secondary end point analysis revealed concomitant drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with placebo, respectively). Improvement in quality of life was reported by 16 of 29 evaluated patients in the phosphatidylcholine group compared with two of 30 in the placebo group (p = 0.00005). Conclusion: Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis. PMID:15951544

  11. Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment

    PubMed Central

    Conigliaro, P; Triggianese, P; Perricone, C; Chimenti, M S; Di Muzio, G; Ballanti, E; Guarino, M D; Kroegler, B; Gigliucci, G; Grelli, S; Perricone, R

    2014-01-01

    Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good–moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment. PMID:24666401

  12. IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.

    PubMed

    Weber, F; Fontaine, B; Cournu-Rebeix, I; Kroner, A; Knop, M; Lutz, S; Müller-Sarnowski, F; Uhr, M; Bettecken, T; Kohli, M; Ripke, S; Ising, M; Rieckmann, P; Brassat, D; Semana, G; Babron, M-C; Mrejen, S; Gout, C; Lyon-Caen, O; Yaouanq, J; Edan, G; Clanet, M; Holsboer, F; Clerget-Darpoux, F; Müller-Myhsok, B

    2008-04-01

    Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated. PMID:18354419

  13. Ra: The Sun for Science and Humanity

    NASA Technical Reports Server (NTRS)

    1996-01-01

    To guide the development of the Ra Strategic Framework, we defined scientific and applications objectives. For our primary areas of scientific interest, we choose the corona, the solar wind, the Sun's effect on the Earth, and solar theory and model development. For secondary areas of scientific interest, we selected sunspots, the solar constant, the Sun's gravitational field, helioseismology and the galactic cosmic rays. We stress the importance of stereoscopic imaging, observations at high spatial, spectral, and temporal resolutions, as well as of long duration measurements. Further exploration of the Sun's polar regions is also important, as shown already by the Ulysses mission. From an applications perspective, we adopted three broad objectives that would derive complementary inputs for the Strategic Framework. These were to identify and investigate: possible application spin-offs from science missions, possible solar-terrestrial missions dedicated to a particular application, and possible future applications that require technology development. The Sun can be viewed as both a source of resources and of threats. Our principal applications focus was that of threat mitigation, by examining ways to improve solar threat monitoring and early warning systems. We compared these objectives to the mission objectives of past, current, and planned international solar missions. Past missions (1962-1980) seem to have been focused on improvement of scientific knowledge, using multiple instrument spacecraft. A ten year gap followed this period, during which the results from previous missions were analyzed and solar study programmes were prepared in international organizations. Current missions (1990-1996) focus on particular topics such as the corona, solar flares, and coronal mass ejections. In planned missions, Sun/Earth interactions and environmental effects of solar activity are becoming more important. The corona is the centre of interest of almost all planned missions

  14. Smartphone application for rheumatoid arthritis self-management: cross-sectional study revealed the usefulness, willingness to use and patients' needs.

    PubMed

    Azevedo, Rita; Bernardes, Miguel; Fonseca, João; Lima, Aurea

    2015-10-01

    Patient-centered smartphone applications have potential to support rheumatoid arthritis (RA) self-management but remain almost unexplored in literature. Therefore, this study evaluated the usefulness of a smartphone application to support RA self-management, the willingness of RA patients to use and pay for it and the features the application should have. In this cross-sectional study, a questionnaire was developed to collect information on population, device ownership, usefulness and willingness to use and pay for a RA self-management application and application features. Descriptive statistics, Chi-square, Fisher's exact test, t test or Mann-Whitney's test and multivariate analysis were used. One hundred RA patients answered the questionnaire. Patients' mean age was 57 ± 11.9 years, most were females (91 %), with multiple drug regimens and a 40 % treatment non-compliance rate. Most patients believed that could have a more active role in self-management (94 %) and reported it would be useful to develop a RA self-management application (86 %). Patients willing to use an application (83 %) were younger, with a possible more active role in self-management, with access to a smartphone, and using short message service, electronic mail and Internet. Multivariate analysis confirmed these results, except the associations regarding access to a smartphone and use of electronic mail and Internet. Fifty-eight patients (82 %) were willing to pay for a RA self-management application and the most requested feature for it was information in a simple format. This study suggested the usefulness and patients' willingness to use and pay for a RA self-management application and provided insight on patients' needs. PMID:25903352

  15. Relationship between air pollution and positivity of RA-related autoantibodies in individuals without established RA: a report on SERA

    PubMed Central

    Gan, Ryan W; Deane, Kevin D; Zerbe, Gary O; Demoruelle, M Kristen; Weisman, Michael H; Buckner, Jane H; Gregersen, Peter K; Mikuls, Ted R; O’Dell, James R; Keating, Richard M; Holers, V Michae; Norris, Jill M

    2013-01-01

    Introduction Studies suggest that respiratory exposures including smoking, proximity to traffic and air pollution might be associated with development of rheumatoid arthritis (RA). RA-related autoantibodies are predictive of the development of RA. Objective We evaluated the relationship between RA-related autoantibodies and exposure to particulate matter (PM), a measure of air pollution of interest to health, in individuals without RA. Methods The Studies of the Etiology of Rheumatoid Arthritis (SERA) is a multicentre study following first-degree relatives (FDRs) of a proband with RA. FDRs are without the 1987 ACR (American College of Rheumatology) classifiable RA at enrolment and are followed for the development of RA-related autoimmunity. RA-related autoantibody outcomes as well as tender and swollen joint outcomes were assessed. Exposure to PM was assigned using ambient air pollution monitoring data and interpolated with inverse distance weighting spatial analyses using Geographic Information Systems. PM exposures were linked to FDR’s residential zip codes. Results RA-related autoantibodies as well as tender or swollen joints are not associated with ambient PM concentrations. Discussion While other respiratory exposures may be associated with increased risk of RA, our data suggest that ambient PM is not associated with autoantibodies and joint signs among individuals without RA, but at increased risk of developing RA. PMID:23572338

  16. Rheumatoid arthritis and sexuality: A patient survey in France

    PubMed Central

    2012-01-01

    Background The objective of this study was to evaluate the impact of rheumatoid arthritis (RA) on patients’ sexuality and identify disease and other factors such as fatigue that most influence sexual relationships. Methods A specific pretested questionnaire was sent to all members of a French patient association (ANDAR). Questions related to demographics, disease status, quality of life (utility, EQ-5D), pain, psychological status (mood), fatigue and emotional and sexual relationships. To isolate the impact of RA, an attempt was made to include a matched sample from the general population. Results The analysis included 1271 patients, but only 70 controls agreed to participate and comparisons should therefore be considered with caution. The two groups were similar in terms of age, gender distribution, living conditions and diseases other than RA. However, patients scored worse for global health, mood, fatigue, had a lower utility (0.55 versus 0.65). Controls were more active sexually (69% versus 63%), in particular women (71% versus 60%). Age, gender, living alone, physical function and mood were significant predictors for being sexually active for patients; for controls, age and overall quality of life (utility) were significant predictors. Conclusions While it is known that RA has a negative impact on patients’ sexuality, there have been few attempts to quantify the problem. Our study highlights the negative impact of RA on patients’ sexuality, and triggers the question how to include this aspect into care. PMID:22963081

  17. Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study.

    PubMed

    Koh, K T; Teh, C L; Cheah, C K; Ling, G R; Yong, M C; Hong, H C; Gun, S C

    2016-01-01

    The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients. PMID:27608797

  18. Evidence for brain glial activation in chronic pain patients

    PubMed Central

    Loggia, Marco L.; Chonde, Daniel B.; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R.; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D.; Zürcher, Nicole R.; Albrecht, Daniel S.; Vangel, Mark G.; Rosen, Bruce R.; Napadow, Vitaly; Hooker, Jacob M.

    2015-01-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand 11C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for 11C-PBR28, nine patient–control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29–63 for patients and 28–65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions. PMID:25582579

  19. Dynamic hyperinflation during activities of daily living in COPD patients.

    PubMed

    Silva, Cláudia S; Nogueira, Fabiana R; Porto, Elias F; Gazzotti, Mariana R; Nascimento, Oliver A; Camelier, Aquiles; Jardim, José R

    2015-08-01

    The objective of this study was to investigate whether some activities of daily living (ADLs) usually related to dyspnea sensation in patients with chronic obstructive pulmonary disease (COPD) are associated with dynamic lung hyperinflation (DH) and whether the use of simple energy conservation techniques (ECTs) might reduce this possible hyperinflation. Eighteen patients (mean age: 65.8 ± 9.8 years) with moderate-to-severe COPD performed six ADLs (walking on a treadmill, storing pots, walking 56 meters carrying a 5-kilogram weight, climbing stairs, simulating taking a shower, and putting on shoes) and had their inspiratory capacity (IC) measured before and after each task. The patients were moderately obstructed with forced expiratory volume in 1 second (FEV1): 1.4 ± 0.4 L (50% ± 12.4); FEV1/forced vital capacity: 0.4 ± 8.1; residual volume/total lung capacity: 52.7 ± 10.2, and a reduction in IC was seen after all six activities (p < 0.05): (1) going upstairs, 170 mL; (2) walking 56 meters carrying 5 kilogram weight, 150 mL; (3) walking on a treadmill without and with ECT, respectively, 230 mL and 235 mL; (4) storing pots without and with ECT, respectively, 170 mL and 128 mL; (5) taking a shower without and with ECT, respectively, 172 mL and 118 mL; and (6) putting on shoes without and with ECT, respectively, 210 mL and 78 mL). Patients with moderate to severe COPD develop DH after performing common ADLs involving the upper and lower limbs. Simple ECTs may avoid DH in some of these ADLs. PMID:25896955

  20. Active core rewarming avoids bioelectrical impedance changes in postanesthetic patients

    PubMed Central

    2011-01-01

    Background Postoperative hypothermia is a common cause of complications in patients who underwent laparoscopic cholecystectomy. Hypothermia is known to elicit electrophysiological, biochemical, and cellular alterations thus leading to changes in the active and passive membrane properties. These changes might influence the bioelectrical impedance (BI). Our aim was to determine whether the BI depends on the core temperature. Methods We studied 60 patients (52 female and 8 male) age 40 to 80 years with an ASA I-II classification that had undergone laparoscopic cholecystectomy under balanced inhalation anesthesia. The experimental group (n = 30) received active core rewarming during the transanesthetic and postanesthesic periods. The control group (n = 30) received passive external rewarming. The BI was recorded by using a 4-contact electrode system to collect dual sets of measurements in the deltoid muscle. The body temperature, hemodynamic variables, respiratory rate, blood-gas levels, biochemical parameters, and shivering were also measured. The Mann-Whitney unpaired t-test was used to determine the differences in shivering between each group at each measurement period. Measurements of body temperature, hemodynamics variables, respiratory rate, and BI were analyzed using the two-way repeated-measures ANOVA. Results The gradual decrease in the body temperature was followed by the BI increase over time. The highest BI values (95 ± 11 Ω) appeared when the lowest values of the temperature (35.5 ± 0.5°C) were reached. The active core rewarming kept the body temperature within the physiological range (over 36.5°C). This effect was accompanied by low stable values (68 ± 3 Ω) of BI. A significant decrease over time in the hemodynamic values, respiratory rate, and shivering was seen in the active core-rewarming group when compared with the controls. The temporal course of shivering was different from those of body temperatue and BI. The control patients showed a

  1. Changes in Plasma IL-6, Plasma VEGF and Serum YKL-40 During Treatment with Etanercept and Methotrexate or Etanercept Alone in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy

    PubMed Central

    Knudsen, Lene Surland; Hetland, Merete Lund; Johansen, Julia Sidenius; Skjødt, Henrik; Peters, Niels Daugaard; Colic, Ada; Grau, Karin; Nielsen, Hans Jørgen; Østergaard, Mikkel

    2009-01-01

    Changes in plasma IL-6, plasma VEGF and serum YKL-40 were determined in rheumatoid arthritis (RA) patients during treatment with etanercept alone or in combination with methotrexate. Twenty-five patients with active RA (DAS28 ≥ 3.2) were randomized to receive etanercept (25 mg sc. biweekly) plus methotrexate (n = 12) or etanercept alone (n = 13). Plasma IL-6, plasma VEGF and serum YKL-40 were determined by ELISA. The 3 biomarkers and DAS28 scores were evaluated at baseline and after 4, 8, 12 and 16 weeks of treatment. At inclusion all patients had significantly (p < 0.001) elevated plasma IL-6, plasma VEGF and serum YKL-40 compared to healthy subjects. Eighteen patients responded to treatment (pooled data from both treatment groups), and they had significant (p < 0.05 to p < 0.001) decreases in plasma IL-6, plasma VEGF, serum YKL-40, ESR and DAS28 after 4 weeks of treatment and throughout the study (except serum YKL-40 at week 16). Plasma IL-6 showed the largest reductions. Non-responders had unchanged biomarkers. At week 16 the patients with DAS28 < 3.2 had lower levels compared to baseline values in plasma IL-6 (p = 0.005), plasma VEGF (p = 0.014), and ESR (p = 0.024). Plasma IL-6, plasma VEGF and serum YKL-40, which reflect different aspects of the inflammatory process, may provide useful information regarding early differentiation of responders from non-responders. PMID:20029652

  2. Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives

    PubMed Central

    Sparks, Jeffrey A.; Iversen, Maura D.; Kroouze, Rachel Miller; Mahmoud, Taysir G.; Triedman, Nellie A.; Kalia, Sarah S.; Atkinson, Michael L.; Lu, Bing; Deane, Kevin D.; Costenbader, Karen H.; Green, Robert C.; Karlson, Elizabeth W.

    2014-01-01

    We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. PMID:25151341

  3. Aryl Hydrocarbon Receptor Antagonism Attenuates Growth Factor Expression, Proliferation, and Migration in Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis

    PubMed Central

    Lahoti, Tejas S.; Hughes, Jarod M.; Kusnadi, Ann; John, Kaarthik; Zhu, Bokai; Murray, Iain A.; Gowda, Krishne; Peters, Jeffrey M.; Amin, Shantu G.

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease with high morbidity and mortality. Within the inflammatory milieu, resident fibroblast-like synoviocytes (FLS) in the synovial tissue undergo hyperplasia, which leads to joint destruction. Epidemiologic studies and our previous research suggest that activation of the aryl hydrocarbon receptor (AHR) pathway plays an instrumental role in the inflammatory and destructive RA phenotype. In addition, our recent studies implicate the AHR in the regulation of the expression of several growth factors in established tumor cell lines. Thus, under inflammatory conditions, we hypothesized that the AHR is involved in the constitutive and inducible expression of several growth factors, FLS proliferation and migration, along with protease-dependent invasion in FLS from patients with RA (RA-FLS). Treatment with the AHR antagonist GNF351 inhibits cytokine-induced expression of vascular endothelial growth factor-A (VEGF-A), epiregulin, amphiregulin, and basic fibroblast growth factor mRNA through an AHR-dependent mechanism in both RA-FLS and FLS. Secretion of VEGF-A and epiregulin from RA-FLS was also inhibited upon GNF351 treatment. RA-FLS cell migration, along with cytokine-induced RA-FLS cell proliferation, was significantly attenuated by GNF351 exposure. Treatment of RA-FLS with GNF351 mitigated cytokine-mediated expression of matrix metalloproteinase-2 and -9 mRNA and diminished the RA-FLS invasive phenotype. These findings indicate that inhibition of AHR activity may be a viable therapeutic target in amelioration of disease progression in RA by attenuating growth factor release; FLS proliferation, migration, and invasion; and inflammatory activity. PMID:24309559

  4. Muscle activation patterns in patients with recurrent shoulder instability

    PubMed Central

    Jaggi, Anju; Noorani, Ali; Malone, Alex; Cowan, Joseph; Lambert, Simon; Bayley, Ian

    2012-01-01

    Purpose: The aim of this study is to present muscle patterns observed with the direction of instability in a series of patients presenting with recurrent shoulder instability. Materials and Methods: A retrospective review was carried out on shoulder instability cases referred for fine wire dynamic electromyography (DEMG) studies at a specialist upper limb centre between 1981 and 2003. An experienced consultant clinical neurophysiologist performed dual needle insertion into four muscles (pectoralis major (PM), latissimus dorsi (LD), anterior deltoid (AD) and infraspinatus (IS)) in shoulders that were suspected to have increased or suppressed activation of muscles that could be contributing to the instability. Raw EMG signals were obtained while subjects performed simple uniplanar movements of the shoulder. The presence or absence of muscle activation was noted and compared to clinical diagnosis and direction of instability. Results: A total of 140 (26.6%) shoulders were referred for fine wire EMG, and 131 studies were completed. Of the shoulders tested, 122 shoulders (93%) were identified as having abnormal patterns and nine had normal patterns. PM was found to be more active in 60% of shoulders presenting with anterior instability. LD was found to be more active in 81% of shoulders with anterior instability and 80% with posterior instability. AD was found to be more active in 22% of shoulders with anterior instability and 18% with posterior instability. IS was found to be inappropriately inactive in only 3% of shoulders with anterior instability but in 25% with posterior instability. Clinical assessment identified 93% of cases suspected to have muscle patterning, but the specificity of the clinical assessment was only correct in 11% of cases. Conclusion: The DEMG results suggest that increased activation of LD may play a role in both anterior and posterior shoulder instability; increased activation of PM may play a role in anterior instability. PMID:23493512

  5. High tibial osteotomies in the young active patient

    PubMed Central

    Traub, Shaun; Efird, Chad

    2010-01-01

    Unicompartmental changes in the knee of a young athlete remains a difficult and controversial problem in orthopaedics. Excessive premature loading of articular cartilage, most often the result of a knee injury, has been shown to result in increased degenerative changes and pain in the younger patient. Instability may also contribute to the degeneration of cartilage and must therefore be considered in the treatment of osteoarthritis in the young adult. High tibial osteotomy has been described as a treatment option for malalignment in the older, less active adult and has shown promising results in a younger, more active population. Osteotomies for instability are more controversial and should be considered in more complex injury patterns. PMID:20076957

  6. Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis.

    PubMed

    Carpenter, A B; Eisenbeis, C H; Carrabis, S; Brown, M C; Ip, S H

    1990-01-01

    Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA. PMID:2313471

  7. Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

    PubMed

    Wang, Fei; Chen, Fang-Fang; Gao, Wen-Bo; Wang, Hai-Yong; Zhao, Ning-Wei; Xu, Min; Gao, De-Yu; Yu, Wei; Yan, Xiao-Ling; Zhao, Jian-Ning; Li, Xiao-Jun

    2016-09-01

    The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA. PMID:27060082

  8. 78 FR 53195 - Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... AFFAIRS Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request... patient satisfaction with VA's dental services. DATES: Written comments and recommendations on the... refer to ``OMB Control No. 2900-0764 (Dental Patient Satisfaction Survey)'' in any...

  9. Resting state activity in patients with disorders of consciousness

    PubMed Central

    Soddu, Andrea; Vanhaudenhuyse, Audrey; Demertzi, Athena; Bruno, Marie-Aurélie; Tshibanda, Luaba; Di, Haibo; Boly, Mélanie; Papa, Michele; Laureys, Steven; Noirhomme, Quentin

    Summary Recent advances in the study of spontaneous brain activity have demonstrated activity patterns that emerge with no task performance or sensory stimulation; these discoveries hold promise for the study of higher-order associative network functionality. Additionally, such advances are argued to be relevant in pathological states, such as disorders of consciousness (DOC), i.e., coma, vegetative and minimally conscious states. Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network. However, the two main approaches employed in the analysis of resting state functional connectivity data (i.e., hypothesis-driven seed-voxel and data-driven independent component analysis) present multiple methodological difficulties, especially in non-collaborative DOC patients. Improvements in motion artifact removal and spatial normalization are needed before fMRI resting state data can be used as proper biomarkers in severe brain injury. However, we anticipate that such developments will boost clinical resting state fMRI studies, allowing for easy and fast acquisitions and ultimately improve the diagnosis and prognosis in the absence of DOC patients’ active collaboration in data acquisition. PMID:21693087

  10. Immune Recognition of Citrullinated Proteoglycan Aggrecan Epitopes in Mice with Proteoglycan-Induced Arthritis and in Patients with Rheumatoid Arthritis

    PubMed Central

    Markovics, Adrienn; Ocskó, Tímea; Katz, Robert S.; Buzás, Edit I.; Glant, Tibor T.

    2016-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting the joints. Anti-citrullinated protein antibodies (ACPA) are frequently found in RA. Previous studies identified a citrullinated epitope in cartilage proteoglycan (PG) aggrecan that elicited pro-inflammatory cytokine production by RA T cells. We recently reported the presence of ACPA-reactive (citrullinated) PG in RA cartilage. Herein, we sought to identify additional citrullinated epitopes in human PG that are recognized by T cells or antibodies from RA patients. Methods We used mice with PG-induced arthritis (PGIA) as a screening tool to select citrulline (Cit)-containing PG peptides that were more immunogenic than the arginine (R)-containing counterparts. The selected peptide pairs were tested for induction of pro-inflammatory T-cell cytokine production in RA and healthy control peripheral blood mononuclear cell (PBMC) cultures using ELISA and flow cytometry. Anti-Cit and anti-R peptide antibodies were detected by ELISA. Results Splenocytes from mice with PGIA exhibited greater T-cell cytokine secretion in response to the Cit than the R version of PG peptide 49 (P49) and anti-P49 antibodies were found in PGIA serum. PBMC from ACPA+ and ACPA- RA patients, but not from healthy controls, responded to Cit49 with robust cytokine production. High levels of anti-Cit49 antibodies were found in the plasma of a subset of ACPA+ RA patients. Another PG peptide (Cit13) similar to the previously described T-cell epitope induced greater cytokine responses than R13 by control (but not RA) PBMC, however, anti-Cit13 antibodies were rarely detected in human plasma. Conclusions We identified a novel citrullinated PG epitope (Cit49) that is highly immunogenic in mice with PGIA and in RA patients. We also describe T-cell and antibody reactivity with Cit49 in ACPA+ RA. As citrullinated PG might be present in RA articular cartilage, Cit PG epitope-induced T-cell activation or antibody deposition may

  11. Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions.

    PubMed

    Savolainen, Laura E; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara

    2016-01-01

    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential. PMID:27379100

  12. Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions

    PubMed Central

    Savolainen, Laura E.; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara

    2016-01-01

    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette–Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential. PMID:27379100

  13. MHEALTH INTERVENTION DEVELOPMENT TO SUPPORT PATIENTS WITH ACTIVE TUBERCULOSIS

    PubMed Central

    Iribarren, Sarah J.; Beck, Susan L.; Pearce, Patricia F.; Chirico, Cristina; Etchevarria, Mirta; Rubinstein, Fernando

    2015-01-01

    Background Mobile Health (mHealth) based interventions have been increasingly used to improve a broad range of health outcomes. However, few researchers have reported on the process or the application of theory to guide the development of mHealth based interventions, or specifically for tuberculosis (TB) treatment management. Aims To describe the steps, process, and considerations in developing a text messaging-based intervention to promote treatment adherence and provide support to patients with active TB. Methods Traditional qualitative techniques, including semi-structured interviews, field notes, content analysis, iterative coding, and thematic analysis, were used to design and document the intervention development with a multidisciplinary team of researchers, clinicians, administrators, and patients who were in active TB treatment. The Information-Motivation-Behavioral Skills (IMB) model was used to guide the coding scheme for content analysis of patient-directed TB educational material and intervention development. Results The development steps included: a) establishing intervention components, including justifications, considerations, timing and frequency of components; b) developing educational messages, including cultural adaption, text or short message service (SMS) formatting, and prioritizing message delivery order; and c) determining implementation protocol. A set of 16 IMB-based messages were developed for the educational component. Final intervention development was achieved in 3 months. Conclusion A collaborative approach and application of a theory to guide the intervention design and development is supported. Although a collaborative approach was more time consuming, it resulted in a more responsive, culturally appropriate, and comprehensive intervention. Considerations for developing a text messaging based intervention are provided and may serve as a guide for similar interventions. Further empirical evidence is needed for applying the IMB model

  14. Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankylosing spondylitis without respiratory symptoms.

    PubMed

    Ayhan-Ardic, F Figen; Oken, Oznur; Yorgancioglu, Z Rezan; Ustun, Nilgun; Gokharman, F Dilek

    2006-03-01

    Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has been detected increasingly by using highly sensitive diagnostic techniques such as high-resolution computed tomography (HRCT). However, HRCT findings in healthy controls and the effects of smoking and drugs have not been well studied. The aim of this controlled study was to evaluate the relationships between disease-specific clinical, laboratory, HRCT and pulmonary function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS patients using sulphasalazine who were non-smokers and exhibited asymptomatic respiratory signs. For this purpose, a total of 60 persons (40 patients and 20 healthy controls) were included in this study. A restrictive pattern on PFT was detected in four patients (20%) with AS, one patient with RA and one control (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had positive HRCT findings. Only one patient (5%) in the control group had abnormal HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion measurement, the score of the visual analogue scale (VAS) for pain and C-reactive protein (CRP) levels were statistically significantly better in patients with AS having normal HRCT than in those with abnormal findings (p<0.05). There was no correlation detected between HRCT and duration of disease, disease activity markers, functional indexes and PFT in patients with RA and AS. HRCT is a sensitive tool in detecting ILD in patients with RA and AS with no signs and symptoms of pulmonary involvement and may be an integral part of such work-up. However, future prospective studies are needed to better determine if HRCT is in fact a predictor of subsequent MTX toxicity. PMID:16091838

  15. The impact of using musculoskeletal ultrasound imaging and other influencing factors on medication adherence in patients with rheumatoid arthritis: a qualitative study

    PubMed Central

    Kumar, Kanta; Raza, Karim; Gill, Paramjit; Greenfield, Sheila

    2016-01-01

    Background Medication can ease symptoms and limit disease progression in rheumatoid arthritis (RA). Despite this, nonadherence to medication is common in RA. We explored the determinants of high and low adherence to disease-modifying antirheumatic drugs (DMARDs) in patients with RA and provide suggestions on approaches to improving adherence to DMARDs. Methods Patients with RA were identified from those who had previously participated in a questionnaire measuring levels of medication adherence. Twenty patients participated (ten high and ten low adherers, as determined by responses to the Medication Adherence Report Scale). In-depth individual semistructured interviews were undertaken until data saturation was reached. Interviews were transcribed and analyzed using a constant comparative method. Results Four main themes related to adherence were identified: 1) symptom severity; 2) illness perception; 3) perceived benefits and risks of DMARDs; and 4) the quality and quantity of information about RA and DMARDs. In addition, patients’ suggestions about strategies to optimize adherence to DMARDs were captured and they fell within the following themes: 1) musculoskeletal ultrasound to explain the disease process and to provide objective feedback about the extent to which their disease activity is being effectively controlled; 2) better explanations of the consequences of poorly controlled RA; and 3) a good relationship with the health professional. Conclusion Patients’ beliefs about medicines, perceptions about RA, and level of satisfaction with information about DMARDs influenced their adherence to DMARDs. The use of musculoskeletal ultrasound to image the inflamed joint may help to improve patient adherence to DMARDs. PMID:27366054

  16. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    ERIC Educational Resources Information Center

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2016-01-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and…

  17. Prevalence of selected organ-specific autoantibodies in rheumatoid arthritis and primary Sjögren's syndrome patients

    PubMed Central

    Majdan, Maria; Dryglewska, Magdalena; Tabarkiewicz, Jacek

    2015-01-01

    Objectives The aim of the study was to investigate the prevalence of selected organ-specific autoantibodies in rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) patients, and discuss their clinical significance. Material and methods The study included 121 RA and 30 pSS patients. Sera were tested for the presence of autoantibodies to thyroid peroxidase (anti-TPO), thyroglobulin (anti-TG), TSH receptor (TRAbs), mitochondrial antigen M2 (AMA-M2-3E) and gliadin-analogous fusion peptides (anti-GAF(3X)) using the ELISA method. Non-organ-specific antibodies were determined: rheumatoid factor in IgM class, anti-citrullinated peptide antibodies and antinuclear antibodies. The occurrence of antibodies was also examined with regards to RA activity. Results The following autoantibodies were detected in RA patients: anti-TPO – 13 (10.7%), anti-TG – 6 (5%), AMA-M2-3E – 3 (2.5%), anti-GAF(3X) – 5 (4.1%). The respective levels of these autoantibodies in pSS patients were 3 (10%), 2 (6.7%), 4 (13.3%) and 2 (6.7%). Polyautoimmunity was confirmed in 34 RA patients (including 20 cases of autoimmune thyroid disease [AITD]) and in 6 pSS patients (6 cases of AITD). When RA patients were divided into anti-TPO positive and anti-TPO negative groups, we found a statistically significant relationship between groups regarding age and hemoglobin concentration. In pSS patients the anti-TPO positive group was less likely to use immunosuppressive drugs as compared with the anti-TPO negative group. Anti-TPO was significantly more frequently detected in RA + AITD vs. RA, RA + SS + AITD vs. RA and in pSS + AITD vs. pSS patients. Conclusions Organ-specific autoantibodies are relatively frequently observed in patients with RA and pSS. Their presence is connected with the clinical picture of the diseases.

  18. SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

    PubMed Central

    2015-01-01

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials. PMID:24749867

  19. Longitudinal neuropsychological findings in amyloid beta-related angiitis (AβRA): a case report.

    PubMed

    Omisade, Antonina; Rigby, Heather; Easton, Alexander; Phillips, Stephen J; Carter, Sherri L

    2013-01-01

    Amyloid β-related angiitis (AβRA) is a clinicopathological diagnosis of primary central nervous system angiitis theoretically triggered by vascular deposition of amyloid β peptide. Deposits of Aβ are associated with degeneration of the vasculature, thereby increasing risks of a stroke and/or cognitive impairment. Despite this, no prior studies have presented a detailed neuropsychological profile associated with AβRA. We present longitudinal neuropsychological findings for the case of a 58-year-old man with biopsy-diagnosed AβRA. Neuropsychological test results and clinical presentation demonstrated a mild to moderate dysexecutive syndrome implicating dorsolateral frontal and orbitofrontal-subcortical systems involvement. Despite prior reports of cognitive decline following a diagnosis of AβRA, cognitive functioning remained relatively stable over a 15-month period after immunosuppressive treatment. For the most part, objective measures did not demonstrate a measurable change in cognitive functioning, except for a mild decline in memory. There were subjective reports of improvement in cognitive and adaptive functioning from the patient and his spouse over this time period. The clinical significance of these results is discussed in the context of theories of executive dysfunction, and with reference to previously-published cases of AβRA. PMID:23244572

  20. Antischistosomal activity of artemisinin derivatives in vivo and in patients.

    PubMed

    Saeed, Mohamed E M; Krishna, Sanjeev; Greten, Henry Johannes; Kremsner, Peter G; Efferth, Thomas

    2016-08-01

    Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms "artemisinin" and "Schistosoma". Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated. PMID:26902577

  1. Heat Shock Protein 96 is Elevated in Rheumatoid Arthritis and Activates Macrophages primarily via TLR2 Signaling

    PubMed Central

    Huang, Qi-Quan; Sobkoviak, Rudina; Jockheck-Clark, Angela; Shi, Bo; Mandelin, Arthur M.; Tak, Paul Peter; Haines, G Kennith; Nicchitta, Christopher V.; Pope, Richard M.

    2010-01-01

    Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased toll like receptor (TLR) 2 and 4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. Gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. Gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages, and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared to peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNFα and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target. PMID:19342676

  2. [Ultrasound densitometry of the heel bone in the diagnosis of osseous tissue metabolic abnormalities in patients with rheumatoid arthritis].

    PubMed

    Iakimenko, E A; Dets', V V; Tbileli, V V

    2001-01-01

    The implication was studied of such factors as occurrence of the affliction, sex, inflammation activity, joint functional inadequacies, intake of steroids in the development of osteopenia and osteoporosis in patients with rheumatoid arthritis (RA). Determined in the above patients were RRF, SOS, BUA with the aid of the ultrasonic densitometer UBIS 5000 of the DMS (FRANCIUM) firm. Of the 42 examined patients, osteoporosis was identified in 28.5 percent, osteopenia in 45.3 percent of cases, the degree associated with RA duration, inflammation activity, function disorders of the joints favored by intensification of processes of osteal resorption in rheumatoid arthritis. PMID:11881371

  3. Imaging of Ra-223 with a small-pixel CdTe detector

    NASA Astrophysics Data System (ADS)

    Scuffham, J. W.; Pani, S.; Seller, P.; Sellin, P. J.; Veale, M. C.; Wilson, M. D.; Cernik, R. J.

    2015-01-01

    Ra-223 Dichloride (Xofigo™) is a promising new radiopharmaceutical offering survival benefit and palliation of painful bone metastases in patients with hormone-refractory prostate cancer [1]. The response to radionuclide therapy and toxicity are directly linked to the absorbed radiation doses to the tumour and organs at risk respectively. Accurate dosimetry necessitates quantitative imaging of the biodistribution and kinetics of the radiopharmaceutical. Although primarily an alpha-emitter, Ra-223 also has some low-abundance X-ray and gamma emissions, which enable imaging of the biodistribution in the patient. However, the low spectral resolution of conventional gamma camera detectors makes in-vivo imaging of Ra-223 challenging. In this work, we present spectra and image data of anthropomorphic phantoms containing Ra-223 acquired with a small-pixel CdTe detector (HEXITEC) [2] with a pinhole collimator. Comparison is made with similar data acquired using a clinical gamma camera. The results demonstrate the advantages of the solid state detector in terms of scatter rejection and quantitative accuracy of the images. However, optimised collimation is needed in order for the sensitivity to rival current clinical systems. As different dosage levels and administration regimens for this drug are explored in current clinical trials, there is a clear need to develop improved imaging technologies that will enable personalised treatments to be designed for patients.

  4. Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis

    PubMed Central

    Xia, Yunfei; Yin, Rulan; Fu, Ting; Zhang, Lijuan; Zhang, Qiuxiang; Guo, Genkai; Li, Liren; Gu, Zhifeng

    2016-01-01

    Objective Nonadherence in rheumatoid arthritis (RA) patients using disease-modifying antirheumatic drugs (DMARDs) may lead to joint damage and function loss. The aim of this cross-sectional study was to explore Chinese RA patients’ adherence rates and investigate potential risk factors for nonadherence. Methods A total of 122 RA patients were recruited from the Affiliated Hospital of Nantong University from January 2014 to April 2015. Patients were asked to complete a set of standardized self-report questionnaires (Compliance Questionnaire on Rheumatology, Health Assessment Questionnaire, Short Form-36 questionnaire, 28-joint Disease Activity Score, Hospital Anxiety and Depression Scale, and Visual Analog Scale). Independent samples t-tests, chi-square analyses, and logistic regression modeling were used to analyze these data. Results Based on Compliance Questionnaire on Rheumatology, 38% of the patients adhered to DMARDs. Adherence was associated with education, income, depression, and the total number of DMARDs. Other demographic and clinical characteristics were not associated with adherence. Logistic regression models identified income, depression, and the total number of DMARDs as predictors of medication nonadherence. Conclusion In this study, 62% of patients with RA were not adherent to their DMARD prescription. Education, income, depression, and the total number of DMARDs were associated with medication adherence, and income, depression, and the total number of DMARDs were independent predictors of medication adherence in patients with RA. These findings could help medical personnel develop helpful interventions to improve adherence in RA patients by paying more attention to the patients with these accompanying risk factors and, finally, improve RA patients’ quality of life. PMID:27217726

  5. Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products

    PubMed Central

    Paoliello-Paschoalato, Adriana Balbina; Marchi, Larissa Fávaro; de Andrade, Micássio Fernandes; Kabeya, Luciana Mariko; Donadi, Eduardo Antônio; Lucisano-Valim, Yara Maria

    2015-01-01

    Rheumatoid arthritis (RA) is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs). In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i) the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii) the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii) the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation. PMID:26346244

  6. Rheumatoid Arthritis Pharmacotherapies: Do They Have Anti-Atherosclerotic Activity?

    PubMed

    Giles, Jon T

    2016-05-01

    Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD) events, presumably related to a greater burden of atherosclerosis, as well as atherosclerotic plaques that tend to be inflamed and rupture prone. Many of the inflammatory pathways underlying the pathobiology of RA are also recognized contributors to atherosclerosis. Immunomodulation is the mainstay for RA therapy, and a variety of biologic and non-biologic pharmacotherapies are used either singly or in combination to control articular and systemic inflammation and prevent joint destruction. Almost all of these agents have theoretical potential to favorably affect atherogenesis and atherothrombosis, but mechanisms by which they exert effects have been incompletely studied, to date. However, whether clinical control of RA disease activity is associated with a reduction in CVD events regardless of agent used or whether the potency of anti-atherogenic effects varies between disease-modifying anti-rheumatic drugs (DMARDs) is an area of current interest in RA research. More broadly, RA immunotherapies are currently being tested in high-CVD-risk patients in proof-of-concept clinical trials that could alter the paradigm for CVD treatment and prevention in the general population. In this review, we will summarize the current evidence ascribing atheroprotective effects to RA pharmacotherapies. PMID:27032790

  7. Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication

    PubMed Central

    Seok, Su-Jin; Kim, Su-Ji; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young

    2011-01-01

    To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication. PMID:21468253

  8. Relationship between balance and physical activity measured by an activity monitor in elderly COPD patients

    PubMed Central

    Iwakura, Masahiro; Okura, Kazuki; Shibata, Kazuyuki; Kawagoshi, Atsuyoshi; Sugawara, Keiyu; Takahashi, Hitomi; Shioya, Takanobu

    2016-01-01

    Background Little is known regarding the relationship between balance impairments and physical activity in COPD. There has been no study investigating the relationship between balance and objectively measured physical activity. Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients. Materials and methods Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study. We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]). Possible confounders were assessed in the COPD group. The between-group differences in balance test scores and physical activity were analyzed. A correlation analysis and multivariate regression analysis were conducted in the COPD group. Results The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores. The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors. Conclusion Impairments in balance and reductions in physical activity were observed in the COPD group. Deficits in balance are independently associated with physical inactivity. PMID:27445470

  9. Active surveillance for prostate cancer: patient selection and management

    PubMed Central

    Klotz, L.

    2010-01-01

    Screening for prostate cancer using prostate-specific antigen (psa) has been appealing. However, the significant associated decline in prostate cancer mortality comes at the cost of a very high rate of diagnosis, and many patients with indolent, non-life-threatening cancer are exposed to the risk of significant side effects from radical treatment. Most men with favourable-risk prostate cancer are not destined to die of their disease, even in the absence of treatment. The challenge is to identify the subset that harbour more aggressive disease early enough that curative therapy is still a possibility, thereby allowing the others to enjoy improved quality of life, free from the side effects of treatment. This article reviews current research into active surveillance in favourable-risk disease and some of the issues that arise when prostate cancer is monitored rather than being treated immediately. PMID:20882126

  10. Thyroid axis activity and suicidal behavior in depressed patients.

    PubMed

    Duval, Fabrice; Mokrani, Marie-Claude; Lopera, Felix Gonzalez; Diep, Thanh Son; Rabia, Hassen; Fattah, Saïd

    2010-08-01

    The aim of this study was to investigate the relationship between suicidal behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed patients. The serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated before and after 0800 and 2300 h thyrotropin-releasing hormone (TRH) challenges, on the same day, in 95 medication-free DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized controls. Compared to controls: (1) patients with a positive suicide history (PSH; n=53) showed lower basal FT4 (at 0800 h: p<0.005; at 2300 h: p<0.03), but normal FT3 levels, while patients with a negative suicide history (NSH; n=42) showed normal FT4 and FT3 levels; (2) TSH responses to TRH (DeltaTSH) were blunted in NSHs (at 0800 h: p<0.03; at 2300 h: p<0.00001), but not in PSHs; (3) both NSHs and PSHs showed lower DeltaDeltaTSH values (differences between 2300 h-DeltaTSH and 0800 h-DeltaTSH) (p<0.000001 and p<0.003, respectively). Compared to NSHs, basal FT4 levels were reduced in PSHs (at 0800 h: p<0.002; at 2300h: p<0.006). HPT parameters were not significantly different between recent suicide attempters (n=32) and past suicide attempters (n=21). However, compared to controls, recent suicide attempters showed lower 2300 h-DeltaTSH (p<0.04) and DeltaDeltaTSH (p<0.002) values, and lower basal FT4 values (at 0800 h: p<0.006; at 2300 h: p<0.02). Our results, obtained in a large sample of depressed inpatients, indicate that various degrees of HPT axis dysregulation are associated with the history of suicide. PMID:20129737

  11. Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid arthritis

    PubMed Central

    Tsujimura, Shizuyo; Tanaka, Yoshiya

    2015-01-01

    The main purpose of treatment of rheumatoid arthritis (RA) with disease modifying antirheumatic drugs (DMARDs) is to control activation of lymphocytes, although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein (P-gp), a member of ATP-binding cassette transporters, causes drug-resistance by efflux of intracellular drugs. Certain stimuli, such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-box-binding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drug-resistance. However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists (e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gp-mediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA. PMID:26618109

  12. The 'natural' history of active rheumatoid arthritis over 3-6 months--an analysis of patients enrolled into trials of potential disease-modifying anti-rheumatic drugs, and treated with placebo.

    PubMed

    Porter, D R; Capell, H A

    1993-06-01

    The natural history of RA over a period of 6 months is not known, but this is of central importance to the design and interpretation of drug trials of possible DMARDs. We analysed the disease activity of 142 rheumatoid patients who were randomized to receive placebo in five double blind, placebo-controlled trials of possible disease-modifying drugs conducted in a single unit. There was no significant change in ESR, duration of morning stiffness or platelet count over a period of 6 months; the mean change in ESR at 3 months was an increase of 2 mm/h (99% C.I. -3, +7), and only 5% of patients more than halved their ESR over 6 months. There was a small significant fall in articular index over 6 months of placebo treatment. There is no measurable placebo effect on ESR, morning stiffness or platelet count when these are used as measures of disease activity in trials of drug therapy in RA. ESR is an informative, stable measure of disease activity; the duration of morning stiffness may be more useful than the articular index. The use of these results as the basis of a historical cohort to help design future placebo-controlled trials, and to interpret uncontrolled trials of putative anti-rheumatic drugs is discussed. PMID:8508282

  13. Peripheral Endocannabinoid System Activity in Patients Treated With Sibutramine

    PubMed Central

    Engeli, Stefan; Heusser, Karsten; Janke, Jürgen; Gorzelniak, Kerstin; Bátkai, Sándor; Pacher, Pál; Harvey-White, Judith; Luft, Friedrich C.; Jordan, Jens

    2008-01-01

    Objective The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS. Methods and Procedures Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies. Results Body weight was stable during the acute treatment period and decreased by 6.0 ± 0.8 kg in those patients completing 3 months of sibutramine treatment (P < 0.05). Circulating endocannabinoids and the expression of ECS genes did not change with acute or chronic sibutramine treatment. Discussion The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity. PMID:18356837

  14. Symmetric dimethylarginine (SDMA) serum levels in rheumatoid arthritis: correlations with insulin resistance and disease activity scores.

    PubMed

    Dimitroulas, Theodoros; Hodson, James; Sandoo, Aamer; Smith, Jacqueline; Kitas, George D

    2015-09-01

    Vascular abnormalities predisposing to atherosclerosis are present in patients with rheumatoid arthritis (RA) and associate with excess cardiovascular risk. Symmetric dimethylarginine (SDMA), an endogenous inhibitor of nitric oxide (NO) synthase activity, has been recognised as novel risk factor for endothelial dysfunction and cardiovascular disease. We aimed to compare SDMA levels in RA patients and controls and to investigate whether they are influenced by demographic, inflammatory or metabolic factors. Serum SDMA levels were measured in 197 RA individuals [median age: 67 years (quartiles: 59-3), 153 (78 %) females] and 82 controls [median age: 44 years [quartiles: 33-55, 50 (61 %) females]. Routine biochemistry tests, lipid profile, glycemic profile [glucose, insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)], as well as inflammatory markers were measured in all patients. Paired analysis was employed for the comparison of SDMA in two groups and multivariable regression models were performed to identify predictors of SDMA in the RA cohort. SDMA was significantly lower in RA than control patients in both unpaired and paired analyses (P < 0.001 and P = 0.005, respectively), with the magnitude of the difference being similar in both models. QUICKI (P = 0.005) and disease activity score-28 (P = 0.007) were positively related to SDMA in the RA cohort, whilst a negative correlation with renal function (eGFR) was detected (P = 0.005). The molecular explanation of lower serum SDMA is unclear, but the established relationships with indices of disease activity and insulin resistance, may underline the pathogenetic role of the L-arginine/NO pathway dysregulation in the development of atherosclerosis in RA. The biological and clinical importance of SDMA in RA remains to be evaluated in clinical and experimental studies. PMID:25772817

  15. Providers, Payers, The Community, And Patients Are All Obliged To Get Patient Activation And Engagement Ethically Right

    PubMed Central

    Danis, Marion; Solomon, Mildred

    2016-01-01

    Active and engaged patients seek the understanding, knowledge, and skills to promote their own health. Efforts to promote such patient activation and engagement are ethically justified because they are consonant with the well-established principle of respect for persons and, as the evidence shows, because they are likely to produce better outcomes for patients. Yet patient activation and engagement can also go ethically awry if, for example, nonadherent patients are abandoned or are unduly disadvantaged by punitive policies and practices, or if the conditions for successful activation and engagement are missing. In this article we discuss the ethical issues and responsibilities that pertain to patients, clinicians, health care organizations, delivery systems, insurers, payers, and communities. For example, physicians or payers could hold patients blameworthy for not following recommendations, but we suggest that a better approach would be for providers and payers to empower patients to effectively share responsibility for defining goals and achieving them. An ethical approach to patient activation and engagement should place obligations not only on patients but also on clinicians, health care organizations and delivery systems, insurers, and communities. PMID:23381534

  16. Response to 223Ra-dichloride in castration-resistant prostate cancer with bone metastasis: A case report

    PubMed Central

    Cabrera, Montserrat Estorch; Rey, Pablo Maroto; Carrió, Ignasi; Montes, Alberto; López, Diego Alonso

    2016-01-01

    Painful bone metastases are common in prostate cancer, with current treatments including non-steroidal analgesics and opiates, surgery, external beam radiotherapy and bone-targeting β-emitting radiopharmaceuticals. The α-emitting isotope 223Ra-dichloride (Ra-223) has been associated with improved overall survival and increased time to first skeletal-related events in patients with castration-resistant prostate cancer (CRPC) presenting with symptomatic bone metastases. The current study reports the case of a 70-year-old male patient, who was diagnosed with prostate cancer in 1999 upon presentation with increased prostate-specific antigen (PSA) levels and painful bone metastases in the context of CRPC. In November 2010, subsequent to undergoing hormonal blockage, the patient was treated with ketoconazole (200 mg/8 h) followed by 10 cycles of docetaxel (75 mg/m2 every 3 weeks). Following disease progression, the patient received 6 doses of Ra-223 (50 kBq/kg; 1 dose/4 weeks). During this treatment period, an improvement in the patient's symptoms, and levels of bone alkaline phosphatase (BAP) and PSA were noted. Furthermore, Ra-223 was well-tolerated without any relevant bone marrow toxicity. However, 2 months after the administration of the final dose of Ra-223, PSA and BAP levels increased again, and bone pain deteriorated. A bone scan showed stable disease in the previously observed metastatic lesions; however, new lesions simultaneously appeared in different locations, indicating progressive disease. PMID:27446432

  17. Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis

    PubMed Central

    Dong, Liyang; Wang, Xuefeng; Tan, Jun; Li, Hao; Qian, Wei; Chen, Jianguo; Chen, Qiaoyun; Wang, Jun; Xu, Wenlin; Tao, Caihua; Wang, Shengjun

    2014-01-01

    The imbalance of Th17/Treg cell populations has been suggested to be involved in the regulation of rheumatoid arthritis (RA) pathogenesis; however, the mechanism behind this phenomenon remains unclear. Recent studies have shown how microRNAs (miRNAs) are important regulators of immune responses and are involved in the development of a variety of inflammatory diseases, including RA. In this study, we demonstrated that the frequencies of CD3+CD4+IL-17+Th17 cells were significantly higher, and CD4+CD25+FOXP3+ Treg cells significantly lower in peripheral blood mononuclear cells from RA patients. Detection of cytokines from RA patients revealed an elevated panel of pro-inflammatory cytokines, including IL-17, IL-6, IL-1β, TNF-α and IL-22, which carry the inflammatory signature of RA and are crucial in the differentiation and maintenance of pathogenic Th17 cells and dysfunction of Treg cells. However, the level of miR-21 was significantly lower in RA patients, accompanied by the increase in STAT3 expression and activation, and decrease in STAT5/pSTAT5 protein and Foxp3 mRNA levels. Furthermore, lipopolysaccharide stimulation up-regulated miR-21 expression from healthy controls, but down-regulated miR-21 expression from RA patients. Therefore, we speculate that miR-21 may be part of a negative feedback loop in the normal setting. However, miR-21 levels decrease significantly in RA patients, suggesting that this feedback loop is dysregulated and may contribute to the imbalance of Th17 and Treg cells. MiR-21 may thus serve as a novel regulator in T-cell differentiation and homoeostasis, and provides a new therapeutic target for the treatment of RA. PMID:25164131

  18. Ra isotopes as a tracer of sediment-water column exchange in the North Sea

    NASA Astrophysics Data System (ADS)

    Burt, William; Thomas, Helmuth; Pätsch, Johannnes; Omar, Abdirahman; Schrum, Corinna; Daewel, Ute

    2014-05-01

    Quantifying the benthic flux of short-lived radium isotopes (224Ra and 223Ra) provides information regarding the extent, and the dominant processes governing sediment-water column exchange in the North Sea. For this purpose we employed three independent measurement techniques including sediment incubation chambers, water column inventories, and a surface mass-balance. Incubation results from 11 stations indicate significant spatial variability in Radium efflux throughout the North Sea, as well as a strong dependence on the stirring rate of the overlying water column. Both inventory and mass-balance methods yield consistently higher benthic fluxes for the Southern North Sea than incubation-based estimates due to the inability of the laboratory incubations to recreate the in-situ mixing conditions present in the well-mixed Southern North Sea. Furthermore, fluxes in the Southern North Sea are higher than those previously reported in other regions, likely due to high rates of sediment irrigation induced by strong tidal and wind mixing near the interface of permeable sandy sediments. The seasonality of distributions and the magnitudes of both benthic and coastal Ra fluxes are further examined by applying Ra as a passive tracer in the 3-dimensional hydrodynamics of the ECOSMO model. Finally, flux estimates combined with direct measurements of porewater Ra activities yield volume fluxes [L m-2 d-1], which when further applied to porewater concentrations of carbon or nutrient species, can provide important information regarding the role of sediments in North Sea biogeochemistry.

  19. Phenotypic effects of an induced mutation of the ObRa isoform of the leptin receptor★

    PubMed Central

    Li, Zhiying; Ceccarini, Giovanni; Eisenstein, Michael; Tan, Keith; Friedman, Jeffrey Michael

    2013-01-01

    Leptin receptors play critical roles in mediating leptin's pleiotropic effects on mammalian physiology. To date, six splice variants of the leptin receptor gene have been identified [1–3]. These splice variants have identical extracellular leptin binding motifs but different intracellular C termini. The finding that mutations specifically ablating the function of ObRb cause obesity has established a critical role for this isoform in leptin signaling [1,7]. ObRa is the most abundant splicing isoform with a broad tissue distribution [5], and it has been proposed to play roles in regulating leptin bioavailability, CSF (cerebrospinal fluid) transport and function by forming heterodimers with ObRb and also activating signal transduction via JAK2 in-vitro [5–10]. To assess the in-vivo role of ObRa, we generated an ObRa KO mouse by deleting the ObRa-specific exon 19a. Homozygous mutant mice breed normally and are indistinguishable from wild-type mice on regular chow diet, but show a slightly increased basal plasma leptin, a slight improvement of their GTT and a slightly reduced response to systemic leptin administration. These mice also show a modest but statistically significant increase in weight when placed on a high fat diet with a slightly reduced CSF/plasma ratio of leptin. These data suggest that ObRa plays a role in mediating some of leptin's effects but that the phenotypic consequences are modest compared to a deletion of ObRb. PMID:24327953

  20. Epithelial IL-22RA1-Mediated Fucosylation Promotes Intestinal Colonization Resistance to an Opportunistic Pathogen

    PubMed Central

    Pham, Tu Anh N.; Clare, Simon; Goulding, David; Arasteh, Julia M.; Stares, Mark D.; Browne, Hilary P.; Keane, Jacqueline A.; Page, Andrew J.; Kumasaka, Natsuhiko; Kane, Leanne; Mottram, Lynda; Harcourt, Katherine; Hale, Christine; Arends, Mark J.; Gaffney, Daniel J.; Dougan, Gordon; Lawley, Trevor D.

    2014-01-01

    Summary Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22RA1 protects against lethal Citrobacter rodentium infection and chemical-induced colitis by promoting colonization resistance against an intestinal opportunistic bacterium, Enterococcus faecalis. Susceptibility of Il22ra1−/− mice to C. rodentium was associated with preferential expansion and epithelial translocation of pathogenic E. faecalis during severe microbial dysbiosis and was ameloriated with antibiotics active against E. faecalis. RNA sequencing analyses of primary colonic organoids showed that IL-22RA1 signaling promotes intestinal fucosylation via induction of the fucosyltransferase Fut2. Additionally, administration of fucosylated oligosaccharides to C. rodentium-challenged Il22ra1−/− mice attenuated infection and promoted E. faecalis colonization resistance by restoring the diversity of anaerobic commensal symbionts. These results support a model whereby IL-22RA1 enhances host-microbiota mutualism to limit detrimental overcolonization by opportunistic pathogens. PMID:25263220

  1. Cumulative genetic risk and prefrontal activity in patients with schizophrenia.

    PubMed

    Walton, Esther; Turner, Jessica; Gollub, Randy L; Manoach, Dara S; Yendiki, Anastasia; Ho, Beng-Choon; Sponheim, Scott R; Calhoun, Vince D; Ehrlich, Stefan

    2013-05-01

    The lack of consistency of genetic associations in highly heritable mental illnesses, such as schizophrenia, remains a challenge in molecular psychiatry. Because clinical phenotypes for psychiatric disorders are often ill defined, considerable effort has been made to relate genetic polymorphisms to underlying physiological aspects of schizophrenia (so called intermediate phenotypes), that may be more reliable. Given the polygenic etiology of schizophrenia, the aim of this work was to form a measure of cumulative genetic risk and study its effect on neural activity during working memory (WM) using functional magnetic resonance imaging. Neural activity during the Sternberg Item Recognition Paradigm was measured in 79 schizophrenia patients and 99 healthy controls. Participants were genotyped, and a genetic risk score (GRS), which combined the additive effects of 41 single-nucleotide polymorphisms (SNPs) from 34 risk genes for schizophrenia, was calculated. These risk SNPs were chosen according to the continuously updated meta-analysis of genetic studies on schizophrenia available at www.schizophreniaresearchforum.org. We found a positive relationship between GRS and left dorsolateral prefrontal cortex inefficiency during WM processing. GRS was not correlated with age, performance, intelligence, or medication effects and did not differ between acquisition sites, gender, or diagnostic groups. Our study suggests that cumulative genetic risk, combining the impact of many genes with small effects, is associated with a known brain-based intermediate phenotype for schizophrenia. The GRS approach could provide an advantage over studying single genes in studies focusing on the genetic basis of polygenic conditions such as neuropsychiatric disorders. PMID:22267534

  2. Characteristics and medical management of patients with rheumatoid arthritis and ankylosing spondylitis.

    PubMed

    Bodur, H; Ataman, S; Akbulut, L; Evcik, D; Kavuncu, V; Kaya, T; Günaydin, R; Kuran, B; Kotevoğlu, N; Bal, A; Aydoğ, E; Altay, Z; Uğurlu, H; Kocabaş, H; Olmez, N; Yazgan, P; Gürsoy, S; Madenci, E; Ozel, S; Delialioğlu, S U

    2008-09-01

    Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, progressive, systemic inflammatory rheumatic diseases that lead to serious disability. The objective of this study was to investigate the demographic and clinical characteristics of the patients with RA and AS who were treated in tertiary hospitals in Turkey and to analyze their current medical management. A total of 562 RA and 216 AS patients were evaluated. The mean age of RA patients was 52.1 +/- 12.6 years. The female to male ratio was 3.7:1. Of the RA patients, 72.2% had positive rheumatoid factor (RF), 62.9% had high C-reactive protein, and 75.2% had radiological erosion. The ratio of patients with Disease Activity Score (DAS) 28 >3.2 was 73.9% and of those with Health Assessment Questionnaire (HAQ) > or =1.5 was 20.9%. There was a statistically significant increase in RF positivity and HAQ scores in the group with higher DAS 28 score. Frequency of extraarticular manifestations was 22.4%. The ratio of the patients receiving disease modifying antirheumatic drugs (DMARD) was 93.1%, and 6.9% of the patients were using anti-tumor necrosis factor (TNF) blocking agents. In AS, the mean age of the patients was 38.1 +/- 10.6, and the female to male ratio was 1:2.5. The time elapsed between the first symptom and diagnosis was 4.3 years. The ratio of peripheral joint involvement was 29.4%. Major histocompatibility complex, class I, B 27 was investigated in 31.1% of patients and the rate of positivity was 91%. In 52.4% of the patients, Bath AS Disease Activity Index (BASDAI) was > or =4. The erythrocyte sedimentation rate, Bath AS Functional Index, and peripheral involvement were significantly higher in the group with BASDAI > or =4. Frequency of extraarticular involvement was 21.2% in AS patients. In the treatment schedule, 77.5% of AS patients were receiving sulphasalazine, 15% methotrexate, and 9.9% anti-TNF agents. Despite widespread use of DMARD, we observed high disease activity in more than

  3. Geology and Topography of Ra Patera, Io, in the Voyager era: Prelude to Eruption

    NASA Technical Reports Server (NTRS)

    Schenk, Paul M.; McEwen, Alfred; Davies, A. G.; Davenport, Trevor; Jones, Kevin; Fessler, Brian

    1997-01-01

    Voyager era stereo images are used to map the geology and topography of Ra Patera (a major active volcanic center and possible site of sulfur eruptions on Io). The summit of Ra Patera reaches only approx.1 km above the surrounding plains. Pre-Voyager-era lava flows occur on slopes of 0.1-0.3 deg, comparable to the lunar mare. These flows were emplaced at either low viscosities, high eruption rates, or both. A 600- km-long ridged mountain unit (rising to approx. 8 km near Carancho Patera) forms a 60 by 90 km wide plateau approx. 0.5 km high 50 km east of Ra Patera. The new lava flows observed by Galileo flowed around the southern edge of this plateau.

  4. Hypothetical hormonal mechanism by which potassium-rich diets benefit patients with rheumatoid arthritis.

    PubMed

    Rastmanesh, Reza

    2009-10-01

    Patients with rheumatoid arthritis (RA) have significantly lower salivary and serum potassium (K) concentration, reduced total body K, and lower dietary K intake than healthy subjects. There may also be a subtle impairment in the hypothalamic-pituitary-adrenal (HPA) axis in patients with RA with both a poor cortisol secretion response as well as a lower adrenocorticotropin hormone (ACTH) response in relation to involved inflammatory factors. Patients with RA also exhibit an impaired Na+, K+-ATPase (NKA) activity which might promote the pro-inflammatory cytokine secretion seen in RA. I will use these facts to support the mechanism I propose. There are no qualitative differences between the effects of endogenous cortisol and exogenously applied synthetic glucocorticoids (GCs), which are widely used to treat RA. All effects are transmitted via the same receptor. The GC, cortisol, plays a role in normal K homeostasis and the reverse is also seen with higher K intake leading to higher cortisol secretion and biosynthesis. Results of a recent clinical trial showed elevated serum cortisol followed K supplementation. I suggest that this is what alleviated RA symptoms. I would like to suggest a "Cortisol-K" theory as a mechanism for De Coti-Marsh's proposed "K theory" while not precluding the possibility of eventual proof of a cure, possibly from effects of K inside cells other than the adrenal glands. PMID:19560875

  5. Physical Activity Enjoyment and Self-Efficacy As Predictors of Cancer Patients' Physical Activity Level

    PubMed Central

    Ungar, Nadine; Wiskemann, Joachim; Sieverding, Monika

    2016-01-01

    Background: Physical activity (PA) can support cancer patients during medical treatment by reducing side-effects and increasing quality of life. However, PA levels mostly decline after diagnosis. Which factors can explain if patients are able to remain or even increase their PA level? Self-efficacy is an important cognitive factor that has been linked to cancer patients' PA across many studies. In contrast, affective factors such as PA enjoyment have rarely been examined. We compare the influence of self-efficacy and PA enjoyment on cancer patients' PA levels after completion of an exercise or stress-management intervention. Methods: Outpatient cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34%, 15%)] were enrolled in the MOTIVACTION study, a 4-week intervention (1 h counseling followed by weekly phone calls), with pre-test (T1), post-test (T2), and a 10-week follow-up (T3). Participants were randomized to either an exercise intervention (emphasizing self-regulatory strategies for behavior change) or to a stress management intervention (coping and relaxation techniques). Sixty-seven patients remained in the study and completed the SQUASH assessment of PA, a measure of maintenance self-efficacy (7 items, Cronbach's α = 0.88) and PA enjoyment (2 items, Cronbach's α = 0.89). Regression analyses were calculated with PA level (at T2 and T3) as dependent variable and relative weight analyses were conducted. The study was registered at clinicalTrials.gov (unique identifier:NCT01576107; URL: https://clinicaltrials.gov/ct2/show/NCT01576107?term=motivaction&rank=1). Results: Baseline self-efficacy and change in PA enjoyment significantly predicted cancer patients' PA level at T2 adjusting for baseline PA and type of intervention. Relative weight (RW) analysis revealed that PA enjoyment (baseline and change together) explained 34.3% of the dependent variable, self-efficacy (baseline and change) explained 38.4%. At follow

  6. Interleukin-18 expression in rheumatoid artheritis synovial tissue and its relation to disease activity.

    PubMed

    Gouda, Elsayed A; Aboulata, Alaa A; Elharoun, Ahmed S; Tawfik, Abdel Hamid; Hossney, Ahmed; Reda, Ali M; Desoky, Khaled M

    2007-01-01

    The study investigates the expression and function of interleukin-18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA). IL-18 and IL-18 receptors (IL-18R) mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). Expression of IL-18 at protein level was analyzed by western blotting technique. Cytokines; (IL-18 and interferon-[IFN-gamma]) in culture supernatants from ST cell organ and synovial cultures and IL-18 in sera and synovial fluid (SF) were measured by ELISA. The ST samples were taken from 44 RA patients and thirty osteoarthritis patients (OA) were included as controls. Using RT-PCR, for ST of RA and OA, mRNA expression of IL-18 was detected in 39 out of 44 (88.6%) RA patients and in 14 out of 30 (46.6%) OA controls. However, mRNA expression of IL-18 R alpha and beta chains were detected in 39 and 35 out of 44 (88.6% and 79.5%) RA patients, respectively. ST of OA did not express mRNA of alpha and beta chains of IL-18 R. In vitro study of IL-18 production by ST showed significantly higher levels in RA compared to that of OA patients (P<0.005). Western blotting revealed that the expression of ST IL-18 was more in RA than in OA (P < 0.02). Only IL-12, but not IL-18, stimulates IFN-gamma production by RAST cells [mean +/- SD = 246 +/- 15 pg/ml]. However, when IL-12 was combined with IL-18, they could significantly stimulate IFN-gamma production by RAST cells [M +/- SD = 629 +/- 18 pg/ml]. OA ST cells did not respond to either IL-12 alone or when combined to IL-18. II-18 was detected at significantly higher levels in sera and SF of RA patients in comparison to OA controls (p < 0.001 and p < 0.01, respectively). IL-18 level in the sera and SF in RA patients was significantly correlated with disease activity. In conclusion, IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by the infiltrating T-cells. These cytokines could play a proinflammatory role in the pathogenesis of RA

  7. Preparing concentrated carrier-free /sup 228/Ra

    SciTech Connect

    Volynskii, L.D.; Garbuzov, V.M.; Tsirlin, V.A.

    1988-05-01

    A scheme has been devised for processing large amounts of old thorium salts to obtain concentrated carrier-free /sup 228/Ra preparations. The process includes simple regeneration of the original thorium salt. The main stages in concentrating the /sup 228/Ra are precipitation and separation of thorium peroxide, isolating the radium with a carrier, ion-exchange separation of the radium from the carrier, and final purification by electrolysis. The /sup 228/Ra recovery is 70%.

  8. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  9. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells.

    PubMed

    Berge, T; Leikfoss, I S; Brorson, I S; Bos, S D; Page, C M; Gustavsen, M W; Bjølgerud, A; Holmøy, T; Celius, E G; Damoiseaux, J; Smolders, J; Harbo, H F; Spurkland, A

    2016-03-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes. PMID:26765264

  10. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

    PubMed Central

    Berge, T; Leikfoss, I S; Brorson, I S; Bos, S D; Page, C M; Gustavsen, M W; Bjølgerud, A; Holmøy, T; Celius, E G; Damoiseaux, J; Smolders, J; Harbo, H F; Spurkland, A

    2016-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes. PMID:26765264

  11. Rapid Pneumatic Transport of Radioactive Samples - RaPToRS

    NASA Astrophysics Data System (ADS)

    Padalino, S.; Barrios, M.; Sangster, C.

    2005-10-01

    Some ICF neutron activation diagnostics require quick retrieval of the activated sample. Minimizing retrieval times is particularly important when the half-life of the activated material is on the order of the transport time or the degree of radioactivity is close to the background counting level. These restrictions exist in current experiments performed at the Laboratory for Laser Energetics, thus motivating the development of the RaPToRS system. The system has been designed to minimize transportation time while requiring no human intervention during transport or counting. These factors will be important if the system is to be used at the NIF where radiological hazards will be present during post activation. The sample carrier is pneumatically transported via a 4 inch ID PVC pipe to a remote location in excess of 100 meters from the activation site at a speed of approximately 7 m/s. It arrives at an end station where it is dismounted robotically from the carrier and removed from its hermetic package. The sample is then placed by the robot in a counting station. This system is currently being developed to measure back-to-back gamma rays produced by positron annihilation which were emitted by activated graphite. Funded in part by the U.S. DOE under sub contract with LLE at the University of Rochester.

  12. Impact of 24 months of anti-TNF therapy versus methotrexate on body weight in patients with rheumatoid arthritis: a prospective observational study.

    PubMed

    Sfriso, Paolo; Caso, Francesco; Filardo, Giuseppe Sebastiano; Botsios, Costantino; Costa, Luisa; Scarpa, Raffaele; Todesco, Silvano; Spinella, Paolo; Oliviero, Francesca; Punzi, Leonardo

    2016-06-01

    To evaluate the impact of anti-TNF-α therapy on the body weight of rheumatoid arthritis (RA) patients following 24 months of treatment. Data were collected on all RA patients included in the Veneto Region's Registry of Biological Therapy from January 2007 to July 2012. Inclusion criteria were: start of monotherapy with adalimumab, etanercept, or methotrexate, no previous use of biologic therapy, and at least 24 months of treatment. At baseline, 12, and 24 months, each patient completed a questionnaire about physical activity, smoking, alcohol, and food habits. One hundred and thirty-one RA patients in monotherapy with etanercept (n = 47), adalimumab (n = 44), and methotrexate (n = 40) were enrolled for this study. After 24 months of therapy, there was an increase of weight only in patients treated with anti-TNF-α. Patients on etanercept and adalimumab therapy showed a risk to gain weight six times greater compared to those on methotrexate therapy. The results of present study show that the use of anti-TNF-α in RA patients can be associated to a significant increase of body weight. This increase is not shown in patients under treatment with methotrexate. A more careful evaluation of weight changes needs to be considered in RA patients under anti-TNF-α treatment. PMID:27048267

  13. Self-cleaning in an estuarine area formerly affected by 226Ra anthropogenic enhancements.

    PubMed

    Absi, A; Villa, M; Moreno, H P; Manjón, G; Periañez, R

    2004-08-15

    The estuary of the Odiel River has been affected by both direct discharges of phosphogypsum (radium enriched industrial waste) and dissolution and weathering of the exposed piles where this radium enriched waste was stored. In 1998 the waste management policy for industries changed. The direct discharges stopped and the new phosphogypsum piles were well protected against dissolution processes, avoiding any transference of radium into the environment. This work presents a study of the evolution with time (1999-2002) of the levels of 226Ra in river water and sediment samples with the new waste management policy. A liquid scintillation technique was used to measure the 226Ra activity concentration in sediment samples. A gas-proportional counter was also used to measure the 226Ra activity concentration in river water samples. The main conclusion is that a systematic and continuous decrease of the activity concentration of 226Ra with time in the Odiel River estuary is occurring. Thus, a possible self-cleaning in the estuary, once the direct waste discharges were avoided, can be inferred. PMID:15262166

  14. Somatotropic, lactotropic and adrenocortical responses to insulin-induced hypoglycemia in patients with rheumatoid arthritis.

    PubMed

    Rovensky, Jozef; Bakosová, Jana; Koska, Juraj; Ksinantová, Lucia; Jezová, Daniela; Vigas, Milan

    2002-06-01

    Neuroendocrine mechanisms have been suggested to play an important role in the onset and progression of rheumatoid arthritis (RA). The aim of this study was to evaluate hypothalamic-pituitary functions in RA patients by measurement of hormone responses to insulin-induced hypoglycemia. Insulin-hypoglycemia (Actrapid HM 0.1 IU/kg, i.v. as a bolus) was induced in 17 male patients and in 11 age-, gender-, and weight-matched healthy subjects. Concentrations of growth hormone (GH), prolactin (PRL) and cortisol were analyzed in plasma. PRL release after thyreoliberin stimulation (TRH, 200 g, i.v.) was determined in 21 patients with active forms of RA and in 12 control subjects to evaluate pituitary lactotropic response. In RA patients, basal concentrations of glucose, GH, PRL, and cortisol were in the normal range and they were comparable to those in the control group. Stress of hypoglycemia induced significant elevation of GH, PRL, and cortisol concentrations in all groups. Cortisol responses to hypoglycemia were comparable in patients and in control subjects. GH release during hypoglycemia was increased (p < 0.05) and PRL response was attenuated (p < 0.05) in RA patients versus control subjects. After TRH administration, PRL response was the same in patients as in healthy subjects. In conclusion, the present study revealed an altered hypothalamic-pituitary function in patients with RA, namely, an enhanced somatotropic and reduced lactotropic activation in response to insulin-induced hypoglycemia. Basal hormone levels and cortisol release during hypoglycemia were similar to those in healthy subjects. PMID:12114282

  15. Treatment of rheumatoid arthritis (RA) in India-how and by whom: results from a speciality clinic-use of low-dose methotrexate (MTX) was inexplicably suboptimal.

    PubMed

    Malaviya, Anand N; Gogia, S B

    2016-09-01

    This study was conducted in order to study (a) seropositive RA patients for their prior caregivers, diagnosis makers, drugs and doses taken and (b) the disease status at the first visit and the last visit, from the standpoint of whether they received optimum or suboptimum DMARD treatment. Prospectively entered data were extracted from a rheumatology-specific electronic health record for demography, diagnostic delay, prior caregivers, diagnosis makers, intake of DMARDs and glucocorticoids and disease activity state at first presentation and at the last visit using structured query language. Among 316 patients, prior caregivers were orthopaedicians (73.4 %), alternative systems of medicine practitioners (62 %), internists (38 %), rheumatologists (35.8 %), general practitioners (17 %) and others (12 %). The diagnosis of RA was made by rheumatologists (55.6 %), orthopaedicians (21 %), internists (12.6 %), physiotherapists (3.5 %), homeopaths (2.8 %), general practitioner (2.1 %), neurologists (1.4 %) and Ayurvedic physicians (0.7 %). The mean and the median diagnostic delay among 142 patients where information was available were 18 and 8.5 months, respectively (SD +23.2). Thirty-two percent of the patients had early disease, 48 % established disease and 20 % late disease at presentation. Sixty-six percent of the patients had taken DMARDs-methotrexate (56 %), hydroxychloroquine (46.2 %), leflunomide (18.7 %) and sulfasalazine (20.6 %)-and often in combinations. Different preparations, doses and schedules of glucocorticoids were taken orally or parentally by 51 %. Only one (0.3 %) patient had taken biological DMARDs prior to visiting this clinic. High or moderate disease activity was present in 84 % at the first clinic visit that fell to 14 % at the last clinic visit. The majority of patients with RA were treated by orthopaedicians and practitioners of alternative systems of medicine with only a third by rheumatologists. In 80 % of patients, the

  16. The Microbial Capsular Polysaccharide Galactoxylomannan Inhibits IL-17A Production in Circulating T Cells from Rheumatoid Arthritis Patients

    PubMed Central

    Pericolini, Eva; Alunno, Alessia; Gabrielli, Elena; Bartoloni, Elena; Cenci, Elio; Chow, Siu-Kei; Bistoni, Giovanni; Casadevall, Arturo; Gerli, Roberto; Vecchiarelli, Anna

    2013-01-01

    The persistence of activated T cells in rheumatoid arthritis (RA) synovium may be attributable to increased homing, increased retention or a possible imbalance between cell proliferation and programmed cell death. Induction of apoptosis may represent a potential therapeutic approach. Galactoxylomannan (GalXM) from the opportunistic fungus Cryptococcus neoformans can interact with T cells and induce T-cell apoptosis through the inhibition of CD45 phosphatase activity. The aim of this study was to determine the effect of GalXM on circulating T cells from patients with RA and the underlying mechanisms. GalXM immunomodulating effect on apoptosis and signal transduction pathway involved in IL-17A production was evaluated on T cells. RA T-cell apoptosis, higher than that of control T cells, was further increased by GalXM through induction of caspase-3 activation. Activated T cells expressing the CD45RO molecule and producing IL-17A were the main target of GalXM-induced apoptosis. GalXM induced consistent impairment of IL-17A production and inhibition of STAT3, which was hyperactivated in RA. In conclusion, GalXM triggered apoptosis of activated memory T cells and interfered with IL-17A production in RA. These data suggest therapeutic targeting of deleterious Th17 cells in RA and other autoimmune diseases. PMID:23308194

  17. Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from patients with rheumatoid arthritis facilitates the inflammatory responses.

    PubMed

    Lu, Ming-Chi; Yu, Hui-Chun; Yu, Chia-Li; Huang, Hsien-Bin; Koo, Malcolm; Tung, Chien-Hsueh; Lai, Ning-Sheng

    2016-04-01

    The aim of this study was to evaluate whether the presence of aberrantly expressed lncRNAs could promote T cell inflammatory responses in patients with RA. The expression levels of 10 potential aberrantly expressed lncRNAs were evaluated in T cells from 39 patients with RA and 17 controls using real-time reverse transcription polymerase chain reaction. The aberrantly expressed lncRNAs were measured in Jurkat cells co-cultured with or without ionomycin and phorbol 12-myristate 13-acetate. Transfection studies using small interfering RNA (siRNA) were conducted for biological functions, and microarray analysis was performed to search for target genes of specific lncRNAs. We confirmed that the expression levels of LOC100652951 and LOC100506036 were higher in RA T cells compared with controls. RA patients treated with biologic agents had lower expression levels of LOC100652951, and female RA patients had lower LOC100506036 expression levels after multivariate analysis. After activation, the expression levels of LOC100506036, but not LOC100652951, increased in Jurkat cells. Transfection of siRNA targeting LOC100506036 inhibited interferon gamma production and the expression of nuclear factor of activated T cells in activated Jurkat cells. After the microarray analysis with validation, inhibition of LOC100506036 expression by siRNA leaded to the decreased expression of sphingomyelin phosphodiesterase 1 (SMPD1). In conclusion, the expression levels of LOC100652951 and LOC100506036 were increased in RA T cells. Treatment with biologic agents could lower the expression of LOC100652951 in RA T cells. LOC100506036 could regulate the expression of SMPD1 and NFAT1 and could contribute to the inflammatory responses in RA. PMID:26616293

  18. Influence of mental practice on upper limb muscle activity and activities of daily living in chronic stroke patients

    PubMed Central

    Park, JuHyung

    2016-01-01

    [Purpose] The aim of this study was to determine the effects of mental practice on muscle activity of the upper extremity and performance of daily activities in chronic stroke patients. [Subjects and Methods] In this research, mental practice was conducted by 2 chronic hemiplegic stroke patients. Mental practice was conducted 30 minutes a day, 5 times a week, for 2 weeks. Evaluation was conducted 4 times before and after intervention. Muscle activity was measured using a surface electromyogram test, and the Modified Barthel Index was used to measure changes in the ability to carry out daily activities. [Results] Both the muscle activity of the upper extremity and capability to perform daily activities showed improved outcomes after mental practice was conducted. [Conclusion] Through this research, mental practice was proven to be effective in improving the muscle activity of upper extremity and capability to perform daily activities in chronic hemiplegic stroke patients. PMID:27134412

  19. 76 FR 56504 - Proposed Information Collection (Spinal Cord Injury Patient Care Survey) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-13

    ... AFFAIRS Proposed Information Collection (Spinal Cord Injury Patient Care Survey) Activity: Comment Request... spinal cord patients' satisfaction with VA rehabilitation and health care system. Affected Public... of automated collection techniques or the use of other forms of information technology. Title:...

  20. Laser trapping of 225Ra and 226Ra with repumping by room-temperature blackbody radiation.

    PubMed

    Guest, J R; Scielzo, N D; Ahmad, I; Bailey, K; Greene, J P; Holt, R J; Lu, Z-T; O'Connor, T P; Potterveld, D H

    2007-03-01

    We have demonstrated Zeeman slowing and capture of neutral 225Ra and 226Ra atoms in a magneto-optical trap. The intercombination transition 1S0-->3P1 is the only quasicycling transition in radium and was used for laser-cooling and trapping. Repumping along the 3D1-->1P1 transition extended the lifetime of the trap from milliseconds to seconds. Room-temperature blackbody radiation was demonstrated to provide repumping from the metastable 3P0 level. We measured the isotope shift and hyperfine splittings on the 3D1-->1P1 transition with the laser-cooled atoms, and set a limit on the lifetime of the 3D1 level based on the measured blackbody repumping rate. Laser-cooled and trapped radium is an attractive system for studying fundamental symmetries. PMID:17359153

  1. Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.

    PubMed Central

    Stichtenoth, D O; Fauler, J; Zeidler, H; Frölich, J C

    1995-01-01

    OBJECTIVES--To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS--Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS--Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS--Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment. PMID:7492221

  2. Retinoic acid inhibits the proliferative response induced by CD40 activation and interleukin-4 in mantle cell lymphoma.

    PubMed

    Guidoboni, Massimo; Zancai, Paola; Cariati, Roberta; Rizzo, Silvana; Dal Col, Jessica; Pavan, Alessandro; Gloghini, Annunziata; Spina, Michele; Cuneo, Antonio; Pomponi, Fabrizio; Bononi, Antonio; Doglioni, Claudio; Maestro, Roberta; Carbone, Antonino; Boiocchi, Mauro; Dolcetti, Riccardo

    2005-01-15

    Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma with poor response to therapy and unfavorable prognosis. Here, we show that retinoic acid (RA) isomers significantly inhibit the proliferation of both primary MCL cultures (n = 7) and established cell lines (Granta 519 and SP-53) as shown by [(3)H]thymidine uptake and carboxyfluorescein diacetate succinimidyl ester labeling coupled with cyclin D1 staining. RA induces cell accumulation in G(0)-G(1) together with a marked up-regulation of p27(Kip1) by inhibiting ubiquitination and proteasome-dependent degradation of the protein. The p21(Cip1) inhibitor was also up-regulated by RA in Granta 519 cells, whereas the expression of cyclin D1 is unaffected. Most of RA-induced p27(Kip1) was bound to cyclin D1/cyclin-dependent kinase 4 complexes, probably contributing to the decreased cyclin-dependent kinase 4 kinase activity and pRb hypophosphorylation observed in RA-treated cells. Experiments with receptor-selective ligands indicate that RA receptor alpha cooperates with retinoid X receptors in mediating RA-dependent MCL cell growth inhibition. Notably, RA isomers, and particularly 9-cis-RA, also inhibited the growth-promoting effect induced in primary MCL cells by CD40 activation alone or in combination with interleukin-4. Immunohistochemical analysis showed that significant numbers of CD40L-expressing lymphoid cells are present in lymph node biopsies of MCL patients. These results therefore further strengthen the possibility that triggering of CD40 by infiltrating CD40L+ cells may continuously promote the growth of MCL cells in vivo. On these grounds, our findings that RA inhibits basal MCL proliferation as well as MCL growth-promoting effects exerted by microenvironmental factors make these compounds highly attractive in terms of potential clinical efficacy in this setting. PMID:15695403

  3. Comparative Analysis Of {sup 226}Ra Soil-To-Plant Transfer In Cabbage Grown In Various Regions

    SciTech Connect

    Madruga, M. J.; Carvalho, F. P.; Silva, L.; Gouveia, J.

    2008-08-07

    The transfer of {sup 226}Ra from soil to cabbage was compared amongst regions, namely the surroundings of Urgeirica uranium milling tailings (GE), regions with past uranium mining activities (GN1), and regions with no uranium mining activities and no uranium deposits (GN2). Results show a slight increase of the concentration ratio values at low radium concentration in soils. Statistical analysis of the mean {sup 226}Ra activity concentrations in soil and cabbage for the three regions was carried out. The comparison of {sup 226}Ra activity concentrations in soils indicated no difference (p>0.05), between GE and GN2 and significant differences (p<0.05) between GE and GN1 and between GN1 and GN2. Similar statistical results were obtained for {sup 226}Ra activity concentrations in cabbage from the same regions. It was concluded that radium Concentration Ratio (CR) for cabbage grown in the region of the main uranium milling site (GE) is of the same order of magnitude of CR in cabagge grown in background regions (GN2). However, {sup 226}Ra CR was higher in cabagge from the region with past uranium mining activities (GN1)

  4. Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis.

    PubMed Central

    Koch, A E; Kunkel, S L; Harlow, L A; Mazarakis, D D; Haines, G K; Burdick, M D; Pope, R M; Walz, A; Strieter, R M

    1994-01-01

    We and others have shown that cells obtained from inflamed joints of rheumatoid arthritis (RA) patients produce interleukin-8, a potent chemotactic cytokine for neutrophils (PMNs). However, IL-8 accounted for only 40% of the chemotactic activity for PMNs found in these synovial fluids. Currently, we have examined the production of the novel PMN chemotactic cytokine, epithelial neutrophil activating peptide-78 (ENA-78), using peripheral blood, synovial fluid, and synovial tissue from 70 arthritic patients. RA ENA-78 levels were greater in RA synovial fluid (239 +/- 63 ng/ml) compared with synovial fluid from other forms of arthritis (130 +/- 118 ng/ml) or osteoarthritis (2.6 +/- 1.8 ng/ml) (P < 0.05). RA peripheral blood ENA-78 levels (70 +/- 26 ng/ml) were greater than normal peripheral blood levels (0.12 +/- 0.04 ng/ml) (P < 0.05). Anti-ENA-78 antibodies neutralized 42 +/- 9% (mean +/- SE) of the chemotactic activity for PMNs found in RA synovial fluids. Isolated RA synovial tissue fibroblasts in vitro constitutively produced significant levels of ENA-78, and this production was further augmented when stimulated with tumor necrosis factor-alpha (TNF-alpha). In addition RA and osteoarthritis synovial tissue fibroblasts as well as RA synovial tissue macrophages were found to constitutively produce ENA-78. RA synovial fluid mononuclear cells spontaneously produced ENA-78, which was augmented in the presence of lipopolysaccharide. Immunohistochemical localization of ENA-78 from the synovial tissue of patients with arthritis or normal subjects showed that the predominant cellular source of this chemokine was synovial lining cells, followed by macrophages, endothelial cells, and fibroblasts. Synovial tissue macrophages and fibroblasts were more ENA-78 immunopositive in RA than in normal synovial tissue (P < 0.05). These results, which are the first demonstration of ENA-78 in a human disease state, suggest that ENA-78 may play an important role in the recruitment of PMNs

  5. Serum Amyloid A as a Marker of Persistent Inflammation and an Indicator of Cardiovascular and Renal Involvement in Patients with Rheumatoid Arthritis

    PubMed Central

    Targońska-Stępniak, Bożena; Majdan, Maria

    2014-01-01

    Objectives. Rheumatoid arthritis (RA) is a systemic, inflammatory disease. Serum amyloid A (SAA) is an acute-phase protein, involved in pathogenesis of atherosclerosis. The aim of the study was to assess serum concentration of SAA in RA patients, with reference to other inflammatory parameters and markers of extra-articular involvement. Methods. The study population consisted of 140 RA patients, low/moderate disease activity (L/MDA) in 98 (70%) patients and high disease activity (HDA) in 42 (30%). Comprehensive clinical and laboratory assessment was performed with evaluation of electrocardiogram and carotid intima-media thickness. Results. The mean SAA concentration [327.0 (263.4) mg/L] was increased highly above the normal value, even in patients with L/MDA. Simultaneously, SAA was significantly higher in patients with HDA versus L/MDA. The mean SAA concentration was significantly higher in patients treated with glucocorticoids, was inversely associated with QTc duration, and was markedly higher in patients with atherosclerotic plaques, emphasizing increased CV risk. SAA was significantly higher in patients with increased cystatin-C level. Conclusions. In RA patients, high serum SAA concentration was strongly associated with activity of the disease and risk of CV and renal involvement. Recurrent assessment of SAA may facilitate searching patients with persistent inflammation and risk of extra-articular complications. PMID:25525305

  6. Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis

    PubMed Central

    Paradowska-Gorycka, Agnieszka; Pawlik, Andrzej; Romanowska-Prochnicka, Katarzyna; Haladyj, Ewa; Malinowski, Damian; Stypinska, Barbara; Manczak, Malgorzata; Olesinska, Marzena

    2016-01-01

    Background Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an “angiogenic disease” because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA. Objectives The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA. Methods 581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA. Results The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was

  7. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities.

    PubMed

    Chen, Jie; Mullins, C Daniel; Novak, Priscilla; Thomas, Stephen B

    2016-02-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and self-determination for their own health and health care. We propose a patient-centered, multilevel activation and empowerment framework (individual-, health care professional-, community-, and health care delivery system-level) to inform the development of culturally informed personalized patient activation and empowerment (P-PAE) interventions to improve population health and reduce racial and ethnic disparities. We discuss relevant Affordable Care Act payment and delivery policy reforms and how they affect patient activation and empowerment. Such policies include Accountable Care Organizations and value-based purchasing, patient-centered medical homes, and the community health benefit. Challenges and possible solutions to implementing the P-PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE measures are needed to conduct comparative effectiveness analyses to evaluate the optimal P-PAE model. We believe the P-PAE model is timely and sustainable and will be critical to engaging patients in their treatment, developing patients' abilities to manage their health, helping patients express concerns and preferences regarding treatment, empowering patients to ask questions about treatment options, and building up strategic patient-provider partnerships through shared decision making. PMID:25845376

  8. Synergistic effects of p38 mitogen-activated protein kinase inhibition with a corticosteroid in alveolar macrophages from patients with chronic obstructive pulmonary disease.

    PubMed

    Armstrong, J; Harbron, C; Lea, S; Booth, G; Cadden, P; Wreggett, K A; Singh, D

    2011-09-01

    Corticosteroids partially suppress cytokine production by chronic obstructive pulmonary disease (COPD) alveolar macrophages. p38 mitogen-activated protein kinase (MAPK) inhibitors are a novel class of anti-inflammatory drug. We have studied the effects of combined treatment with a corticosteroid and a p38 MAPK inhibitor on cytokine production by COPD alveolar macrophages, with the aim of investigating dose-sparing and efficacy-enhancing effects. Alveolar macrophages from 10 patients with COPD, six smokers, and six nonsmokers were stimulated with lipopolysaccharide (LPS) after preincubation with five concentrations of dexamethasone alone, five concentrations of the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796) alone, and all combinations of these concentrations. After 24 h, the supernatants were analyzed for interleukin (IL)-8, IL-6, tumor necrosis factor α (TNFα), granulocyte macrophage-colony-stimulating factor (GM-CSF), IL-1α, IL-1β, IL-1ra, IL-10, monocyte chemoattractant protein 3, macrophage-derived chemokine (MDC), and regulated on activation normal T cell expressed and secreted (RANTES). The effect of dexamethasone on p38 MAPK activation was analyzed by Western blotting. Dexamethasone and BIRB-796 both reduced LPS-induced cytokine production in a dose-dependent manner in all subject groups, with no differences between groups. Increasing the concentration of BIRB-796 in combination with dexamethasone produced progressively greater inhibition of cytokine production than dexamethasone alone. There were significant efficacy-enhancing benefits and synergistic dose-sparing effects (p < 0.05) for the combination treatment for IL-8, IL-6, TNFα, GM-CSF, IL-1ra, IL-10, MDC, and RANTES in one or more subject groups. Dexamethasone had no effect on LPS-induced p38 MAPK activation. We conclude that p38 MAPK activation in alveolar macrophages is corticosteroid-insensitive. Combining a p38

  9. Postmenopausal loss of Ra acquired in adolescence or young adulthood: quantitative relationship to radiation-induced skeletal damage and dosimetric implications

    SciTech Connect

    Keane, A.T.; Rundo, J.; Essling, M.A.

    1988-05-01

    From the results of serial measurements of body /sup 226/Ra activity in 13 former luminous dial workers 30-60 y after relatively brief periods of intake of luminous compounds in adolescence or young adulthood, we determined the postmenopausal rate of elimination of Ra in percent of contemporary body Ra content per year. This rate was negatively correlated with the reduced x-ray score, a measure of radiation osteonecrosis observed radiographically in the 13 subjects (r = -0.85, P less than 0.001). The clearance rates of subjects retaining low Ra activity were greater than predicted by retention models. We conclude that for those members of the Ra-exposed population under study for health effects at our institution who sustained the lesser degrees of macroscopic skeletal damage, present estimates of skeletal absorbed dose are systematically low, by at most a factor of 2.

  10. Postmenopausal loss of Ra acquired in adolescence or young adulthood: quantitative relationship to radiation-induced skeletal damage and dosimetric implications.

    PubMed

    Keane, A T; Rundo, J; Essling, M A

    1988-05-01

    From the results of serial measurements of body 226Ra activity in 13 former luminous dial workers 30-60 y after relatively brief periods of intake of luminous compounds in adolescence or young adulthood, we determined the postmenopausal rate of elimination of Ra in percent of contemporary body Ra content per year. This rate was negatively correlated with the "reduced x-ray score," a measure of radiation osteonecrosis observed radiographically in the 13 subjects (r = -0.85, P less than 0.001). The clearance rates of subjects retaining low Ra activity were greater than predicted by retention models. We conclude that for those members of the Ra-exposed population under study for health effects at our institution who sustained the lesser degrees of macroscopic skeletal damage, present estimates of skeletal absorbed dose are systematically low, by at most a factor of 2. PMID:3360604

  11. Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice

    PubMed Central

    Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice. We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis. CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01–1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17–2.59), RA typical erosion at baseline (95%CI 1.56–21.1), and the introduction of bDMARDs (95%CI 0.06–0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years. We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients’ disease durations. PMID:27124044

  12. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

    SciTech Connect

    Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting; Song, Ran; Wang, Lu; Gu, Yan-Hong; Zeng, Guang-Zhi; Shen, Yan; Wu, Xue-Feng; Tan, Ning-Hua; Xu, Qiang; Sun, Yang

    2013-02-15

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

  13. Enhanced HMGB1 Expression May Contribute to Th17 Cells Activation in Rheumatoid Arthritis

    PubMed Central

    Shi, Yan; Sandoghchian Shotorbani, Siamak; Su, Zhaoliang; Liu, Yanfang; Tong, Jia; Zheng, Dong; Chen, Jianguo; Liu, Yingzhao; Xu, Yan; Jiao, Zhijun; Wang, Shengjun; Lu, Liwei; Huang, Xinxiang; Xu, Huaxi

    2012-01-01

    Rheumatoid arthritis(RA) is a common autoimmune disease associated with Th17 cells, but what about the effect of high-mobility group box chromosomal protein 1 (HMGB1) and the relationship between Th17-associated factors and HMGB1 in RA remains unknown. In the present study, we investigated the mRNA levels of HMGB1, RORγt, and IL-17 in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by quantitative real-time PCR (RT-qPCR), and the concentrations of HMGB1, IL-17, and IL-23 in plasma were detected by ELISA. And then, the effect of HMGB1 on Th17 cells differentiation was analyzed in vitro. Our clinical studies showed that the mRNAs of HMGB1, RORγt, and IL-17 in patients were higher than that in health control (P < 0.05), especially in active RA patients (P < 0.05). The plasma HMGB1, IL-17, and IL-23 in RA patients were also higher than that in health control (P < 0.05); there was a positive correlation between the expression levels of HMGB1 and the amount of CRP, ERS, and RF in plasma. In vitro, the IL-17-produced CD4+T cells were increased with 100 ng/mL rHMGB1 for 12h, which indicated that the increased HMGB1 might contribute to Th17 cells activation in RA patients. PMID:22110531

  14. Clinical and arthroscopic findings in recreationally active patients

    PubMed Central

    2010-01-01

    Objective To examine the diagnostic accuracy of standard clinical tests for the shoulder in recreational athletes with activity related pain. Design Cohort study with index test of clinical examination and reference standard of arthroscopy. Setting Sports Medicine clinic in Sheffield, U.K. Participants 101 recreational athletes (82 male, 19 female; mean age 40.8 ± 14.6 years) over a six year period. Interventions Bilateral evaluation of movements of the shoulder followed by standardized shoulder tests, formulation of clinical diagnosis and shoulder arthroscopy conducted by the same surgeon. Main Outcome Measurements Sensitivity, specificity, likelihood ratio for a positive test and over-all accuracy of clinical examination was examined retrospectively and compared with arthroscopy. Results Isolated pathology was rare, most patients (72%) having more than one injury recorded. O'Brien's clinical test had a mediocre sensitivity (64%) and over-all accuracy (54%) for diagnosing SLAP lesions. Hawkins test and Jobe's test had the highest but still not impressive over-all accuracy (67%) and sensitivity (67%) for rotator cuff pathology respectively. External and internal impingement tests showed similar levels of accuracy. When a positive test was observed in one of a combination of shoulder tests used for diagnosing SLAP lesions or rotator cuff disease, sensitivity increased substantially whilst specificity decreased. Conclusions The diagnostic accuracy of isolated standard shoulder tests in recreational athletes was over-all very poor, potentially due to the majority of athletes (71%) having concomitant shoulder injuries. Most likely, this means that many of these injuries are missed in general practice and treatment is therefore delayed. Clinical examination of the shoulder should involve a combination of clinical tests in order to identify likely intra articular pathology which may warrant referral to specialist for surgery. PMID:20157421

  15. What evidence is there for a delay in diagnostic coding of RA in UK general practice records? An observational study of free text

    PubMed Central

    Ford, Elizabeth; Carroll, John; Smith, Helen; Davies, Kevin; Koeling, Rob; Petersen, Irene; Rait, Greta; Cassell, Jackie

    2016-01-01

    Objectives Much research with electronic health records (EHRs) uses coded or structured data only; important information captured in the free text remains unused. One dimension of EHR data quality assessment is ‘currency’ or timeliness, that is, data are representative of the patient state at the time of measurement. We explored the use of free text in UK general practice patient records to evaluate delays in recording of rheumatoid arthritis (RA) diagnosis. We also aimed to locate and quantify disease and diagnostic information recorded only in text. Setting UK general practice patient records from the Clinical Practice Research Datalink. Participants 294 individuals with incident diagnosis of RA between 2005 and 2008; 204 women and 85 men, median age 63 years. Primary and secondary outcome measures Assessment of (1) quantity and timing of text entries for disease-modifying antirheumatic drugs (DMARDs) as a proxy for the RA disease code, and (2) quantity, location and timing of free text information relating to RA onset and diagnosis. Results Inflammatory markers, pain and DMARDs were the most common categories of disease information in text prior to RA diagnostic code; 10–37% of patients had such information only in text. Read codes associated with RA-related text included correspondence, general consultation and arthritis codes. 64 patients (22%) had DMARD text entries >14 days prior to RA code; these patients had more and earlier referrals to rheumatology, tests, swelling, pain and DMARD prescriptions, suggestive of an earlier implicit diagnosis than was recorded by the diagnostic code. Conclusions RA-related symptoms, tests, referrals and prescriptions were recorded in free text with 22% of patients showing strong evidence of delay in coding of diagnosis. Researchers using EHRs may need to mitigate for delayed codes by incorporating text into their case-ascertainment strategies. Natural language processing techniques have the capability to do this at

  16. Paraprofessional Staff in Transition: The Sophomore RA Experience

    ERIC Educational Resources Information Center

    Brandt Brecheisen, Shannon M.

    2015-01-01

    The sophomore resident assistant (RA) experience exists at the point where the sophomore experience and the RA position intersect. Sophomore students contend with specific transition struggles and challenges unique to their class standing as they make decisions about their sense of purpose and future career, and those who choose to become RAs face…

  17. IFNα Serum Levels Are Associated with Endothelial Progenitor Cells Imbalance and Disease Features in Rheumatoid Arthritis Patients

    PubMed Central

    Rodríguez-Carrio, Javier; de Paz, Banesa; López, Patricia; Prado, Catuxa; Alperi-López, Mercedes; Ballina-García, Francisco Javier; Suárez, Ana

    2014-01-01

    Introduction IFNα has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has been linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory conditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNα in endothelial damage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed to evaluate the potential associations of IFNα serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis (RA) patients. Methods pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential CD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic lupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical and immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by reviewing clinical records. Results Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor populations, unless high IFNα levels were present. In fact, the IFNhigh RA patient group (n = 40, 33%), showed increased EPC levels, comparable to SLE patients. In addition, high IFNα serum levels were associated with higher disease activity (DAS28), presence of autoantibodies, higher levels of IL-1β, IL-6, IL-10 and MIP-1α, lower amounts of TGF-β, and increased mEPC/EPC ratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between high IFNα levels and occurrence of CV events observed in RA patients seems to support this hypothesis. Conclusions IFNα serum marker could be used to identify a group of RA patients with increased disease activity, EPC imbalance, enhanced

  18. Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: results from a large Japanese postmarketing surveillance study.

    PubMed

    Koike, Takao; Harigai, Masayoshi; Inokuma, Shigeko; Ishiguro, Naoki; Ryu, Junnosuke; Takeuchi, Tsutomu; Tanaka, Yoshiya; Yamanaka, Hisashi; Fujii, Koichi; Yoshinaga, Takunari; Freundlich, Bruce; Suzukawa, Michio

    2012-06-01

    Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor-α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P < 0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment. PMID:21331576

  19. Regulation of B cell activating factor (BAFF) receptor expression by NF-κB signaling in rheumatoid arthritis B cells

    PubMed Central

    Woo, Yun-Ju; Yoon, Bo-Young; Jhun, Joo-Yeon; Oh, Hye-Jwa; Min, Sewon; Park, Sung-Hwan; Kim, Ho-Youn

    2011-01-01

    B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-κB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-κB p65, NF-κB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-κB inhibitors. NF-κB p65, NF-κB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-κB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-κB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-κB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA. PMID:21515993

  20. Reconstitution of ST2 (IL-1R4) specific for IL-33 activity; no suppression by IL-1Ra though a common chain IL-1R3 (IL-1RAcP) shared with IL-1.

    PubMed

    Jo, Seunghyun; Kim, Eunsom; Kwak, Areum; Lee, Jungmin; Hong, Jaewoo; Lee, Jongho; Youn, Sulah; Bae, Suyoung; Kim, Busun; Ryoo, Soyoon; Kang, Tae-Bong; Her, Erk; Choi, Dong-Ki; Kim, Yong-Sung; Lee, Youngmin; Jhun, Hyunjhung; Kim, Soohyun

    2016-07-01

    Interleukin-33 (IL-33) receptors are composed of ST2 (also known as IL-1R4), a ligand binding chain, and IL-1 receptor accessory protein (IL-1RAcP, also known as IL-1R3), a signal transducing chain. IL-1R3 is a common receptor for IL-1α, and IL-1β, IL-33, and three IL-36 isoforms. A549 human lung epithelial cells are highly sensitive to IL-1α and IL-1β but not respond to IL-33. The lack of responsiveness to IL-33 is due to ST2 expression. ST2 was stably transfected into A549 cells to reconstitute its activity. RT-PCR and FACS analysis confirmed ST2 expression on the cell surface of A549/ST2 cells. Upon IL-33 stimulation, A549/ST2 cells induced IL-8 and IL-6 production in a dose dependent manner while A549/mock cells remained unresponsive. There was no difference in IL-1α and IL-1β activity in A549/ST2 cells compared to A549/mock cells despite the fact that IL-33 shares IL-1R3 with IL-1α/β. IL-33 activated inflammatory signaling molecules in a time- and dose-dependent manner. Anti-ST2 antibody and soluble recombinant ST2-Fc abolished IL-33-induced IL-6 and IL-8 production in A549/ST2 cells but the IL-1 receptor antagonist failed to block IL-33-induced cytokines. This result demonstrates for the first time the reconstitution of ST2 in A549 human lung epithelial cell line and verified its function in IL-33-mediated cytokine production and signal transduction. PMID:27031441

  1. Active Student Participation May Enhance Patient Centeredness: Patients' Assessments of the Clinical Education Ward for Integrative Medicine

    PubMed Central

    Tauschel, Diethard; Neumann, Melanie; Lutz, Gabriele; Valk-Draad, Maria

    2013-01-01

    Objectives. To examine the impact of active student participation on quality of care in an integrative inpatient setting. Methods. Over a two-year period, we surveyed all patients treated on the Clinical Education Ward for Integrative Medicine (CEWIM), where final-year medical students are integrated into an internal medicine ward complementing conventional medicine with anthroposophic medicine. Patients treated on the regular wards of the same internal medicine department served as the control group (CG). General quality of care was studied with the Picker Inpatient Questionnaire, physician empathy with the Consultation and Relational Empathy measure, and patient enablement with the Patient Enablement Index. ANCOVA was used to control for covariates while examining significant differences between both patient groups. Results. Comparison of the CG wards and the CEWIM revealed no significant differences in medical treatment success. The CEWIM, however, achieved better results for physician-patient interaction, physician empathy, and patient enablement. Eighty Percent of the CEWIM patients rated student participation as positively impacting quality of care. Conclusion. Our results indicate that incorporating students in an integrative healthcare setting may result in greater patient centeredness. Further studies are needed to determine whether this is due to organizational advantages, students' empathic activity, the impact of teaching, or learner-teacher interaction. PMID:23573149

  2. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    PubMed Central

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-01-01

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients. PMID:26147422

  3. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    PubMed

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  4. Large 224Ra and 228Ra disequilibrium indicates intense groundwater processes in the Cabo Frio coastal system

    NASA Astrophysics Data System (ADS)

    Souza, Giovana; Silva-Filho, Emmanoel; Sanders, Christian; Marques, Eduardo; Caldeira, Pedro; Santos, Luiz Eduardo; Kutter, Vinicius; Smoak, Joseph

    2014-05-01

    Input of subterranean water, referred to as Submarine Groundwater Discharge (SGD), typically is a mixture of infiltrated seawater and terrestrially derived freshwater and includes all advective fluid flow between the land and the continental shelf, regardless of the source or composition of the fluids (Smoak et al., 2013; Burnett et al., 2003). A substantial flow of nutrient and metal input via SGD, which may contribute to coastal eutrophication, has been document in recent studies (Sanders et al., 2012; Santos et al., 2008). Direct measurements (e.g. seepage meters) of SGD are difficult on a regional scale. However, radium isotopes have been shown to be powerful tools to quantify SGD fluxes and indicate the sources (Sanders et al., 2012). The direct parent of each radium isotope is a thorium isotope. Thorium is strongly adsorbed to sediment and provides a source of radium, which is generated on a range of time scales. In freshwater, radium is strongly adsorbed to particles. However, under reducing conditions, low pH and/or increasing salinity, radium can be released into solution. These characteristics make radium an excellent tracer of brackish SGD and a net flux of nutrients and metals to the ocean. The coastal plain in the region of Cabo Frio and its surroundings consist of Quaternary deposits of continental sediments, coastal lagoons and marine sands forming a large coastal aquifer. During the winter of 2012 and summer of 2013 was performed a physicochemical characterization and measurements of radio isotopes in groundwater along a transect perpendicular to the beach. The high radio activities associated with the imbalance exists between the 224Ra and 228Ra can be useful tools in understanding the role of submarine groundwater discharge in this region highly productive and high marine biodiversity.

  5. Active Patient Participation in the Development of an Online Intervention

    PubMed Central

    van Weel-Baumgarten, Evelyn M; Snippe, Harm Wouter; Gouw, Hans; Zijlstra, Josée M; van Dulmen, Sandra

    2014-01-01

    Background An important and challenging part of living with cancer relates to the repeated visits to the hospital. Since how patients cope between these post-diagnostic visits depends partly on the information and support received from their physician during the visits, it is important to make the most of them. Recent findings reinforce the importance of training not only the health care professionals in communication skills, but providing patients with support in communication as well. Delivering such supportive interventions online can have potential benefits in terms of accessibility, cost-effectiveness, and ability to tailor information to personal needs. However, problems with attrition (dropout, non-usage) during the test phase and poor uptake after implementation are frequently reported. The marginal level of engagement of the patient as end user seems to play a role in this. Therefore, recent research suggests integrating theory-based development methods with methods that promote involvement of the patient at an early stage. This paper describes a participatory protocol, used to let patients guide a theory-informed development process. Objective The objective of this project was to apply a bottom-up inspired procedure to develop a patient-centered intervention with corresponding evaluation and implementation plan. Methods The applied development protocol was based on the intervention mapping framework, combined with patient participatory methods that were inspired by the participation ladder and user-centred design methods. Results The applied protocol led to a self-directed online communication intervention aimed at helping patients gain control during their communications with health care professionals. It also led to an evaluation plan and an implementation plan. The protocol enabled the continuous involvement of patient research partners and the partial involvement of patient service users, which led to valuable insights and improvements. Conclusions

  6. Predictors of infusion reactions during infliximab treatment in patients with arthritis.

    PubMed

    Kapetanovic, Meliha C; Larsson, Lotta; Truedsson, Lennart; Sturfelt, Gunnar; Saxne, Tore; Geborek, Pierre

    2006-01-01

    In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999-2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions. PMID:16869978

  7. Predictors of infusion reactions during infliximab treatment in patients with arthritis

    PubMed Central

    Kapetanovic, Meliha C; Larsson, Lotta; Truedsson, Lennart; Sturfelt, Gunnar; Saxne, Tore; Geborek, Pierre

    2006-01-01

    In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999–2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions. PMID:16869978

  8. Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region

    PubMed Central

    Machado, Daniel A.; Guzman, Renato; Xavier, Ricardo M.; Simon, Jesus A.; Mele, Linda; Shen, Qi; Pedersen, Ronald; Kotak, Sameer; Vlahos, Bonnie

    2016-01-01

    Background: Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited. Objective: To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA. Methods: In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension. Results: In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128. Conclusion: After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile. Trial

  9. Rainfall Manipulation Plot Study (RaMPS)

    DOE Data Explorer

    Blair, John [Kansas State University; Fay, Phillip [USDA-ARS; Knapp, Alan [Colorado State University; Collins, Scott [University of New Mexico; Smith, Melinda [Yale University

    Rainfall Manipulation Plots facility (RaMPs) is a unique experimental infrastructure that allows us to manipulate precipitation events and temperature, and assess population community, and ecosystem responses in native grassland. This facility allows us to manipulate the amount and timing of individual precipitation events in replicated field plots at the Konza Prairie Long-Term Ecological Research (LTER) site. Questions we are addressing include: • What is the relative importance of more extreme precipitation patterns (increased climatic variability) vs. increased temperatures (increased climatic mean) with regard to their impact on grassland ecosystem structure and function? Both projected climate change factors are predicted to decrease soil water availability, but the mechanisms by which this resource depletion occurs differ. • Will altered precipitation patterns, increased temperatures and their interaction increase opportunities for invasion by exotic species? • Will long-term (6-10 yr) trajectories of community and ecosystem change in response to more extreme precipitation patterns continue at the same rate as initial responses from years 1-6? Or will non-linear change occur as potential ecological thresholds are crossed? And will increased temperatures accelerate these responses? Data sets are available as ASCII files, in Excel spreadsheets, and in SAS format. (Taken from http://www.konza.ksu.edu/ramps/backgrnd.html

  10. Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia

    PubMed Central

    de Borst, Gert Jan; Verhaar, Marianne C.; Roest, Mark; Moll, Frans L.

    2015-01-01

    Background Patients with critical limb ischemia (CLI) have a high risk to develop cardiovascular events (CVE). We hypothesized that in CLI patients platelets would display increased baseline activation and reactivity. Objectives We investigated baseline platelet activation and platelet reactivity in patients with CLI. Patients/Methods In this study baseline platelet activation and platelet reactivity in response to stimulation of all major platelet activation pathways were determined in 20 CLI patients (11 using aspirin and 9 using vitamin K-antagonists) included in the Juventas-trial (clinicaltrials.gov NCT00371371) and in 17 healthy controls. Platelet activation was quantified with flow cytometric measurement of platelet P-selectin expression and fibrinogen binding. Results CLI patients not using aspirin showed higher baseline platelet activation compared to healthy controls. Maximal reactivity to stimulation of the collagen and thrombin activation pathway was decreased in CLI patients compared to healthy controls. In line, attenuated platelet reactivity to stimulation of multiple activation pathways was associated with several traditional risk factors for cardiovascular disease. Conclusions Baseline platelet activation was increased in CLI patients, whereas the reactivity of circulating platelets to several stimulatory agents is decreased. Reactivity of platelets was inversely correlated with cardiovascular risk factors. PMID:26148006

  11. IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or systemic lupus erythematosus.

    PubMed

    Tomura, K; Kang, H; Mitamura, K; Takei, M; Karasaki, M; Koyasu, S; Sawada, S

    1989-11-01

    Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE. PMID:2623661

  12. Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

    PubMed Central

    Guillou, Clément; Fréret, Manuel; Fondard, Emeline; Derambure, Céline; Avenel, Gilles; Golinski, Marie-Laure; Verdet, Mathieu; Boyer, Olivier; Caillot, Frédérique; Musette, Philippe; Lequerré, Thierry; Vittecoq, Olivier

    2016-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA. PMID:27025255

  13. The Impact of Inflammation on Metabolomic Profiles in Patients With Arthritis

    PubMed Central

    Young, Stephen P; Kapoor, Sabrina R; Viant, Mark R; Byrne, Jonathan J; Filer, Andrew; Buckley, Christopher D; Kitas, George D; Raza, Karim

    2013-01-01

    Objective. Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We used nuclear magnetic resonance (NMR) spectroscopy–based metabolomics to assess metabolic fingerprints in serum from patients with established rheumatoid arthritis (RA) and those with early arthritis. Methods. Serum samples were collected from newly presenting patients with established RA who were naive for disease-modifying antirheumatic drugs, matched healthy controls, and 2 groups of patients with synovitis of ≤3 months' duration whose outcomes were determined at clinical followup. Serum metabolomic profiles were assessed using 1-dimensional 1H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolomic profiles and clinical variables including outcomes were examined. Results. The serum metabolic fingerprint in established RA was clearly distinct from that of healthy controls. In early arthritis, we were able to stratify the patients according to the level of current inflammation, with C-reactive protein correlating with metabolic differences in 2 separate groups (P < 0.001). Lactate and lipids were important discriminators of inflammatory burden in both early arthritis patient groups. The sensitivities and specificities of models to predict the development of either RA or persistent arthritis in patients with early arthritis were low. Conclusion. The metabolic fingerprint reflects inflammatory disease activity in patients with synovitis, demonstrating that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood. The identification of metabolic alterations may provide insights into disease mechanisms operating in patients with inflammatory arthritis. PMID:23740368

  14. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    PubMed Central

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2015-01-01

    Designing culturally-sensitive personalized interventions is essential to sustain patients’ involvement in their treatment, and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and self-determination for their own health and health care. We propose a patient-centered, multi-level activation and empowerment framework (individual-, health care professional-, community-, and health care delivery system-level) to inform the development of culturally informed personalized patient activation and empowerment (P-PAE) interventions to improve population health, and reduce racial and ethnic disparities. We discuss relevant Affordable Care Act payment and delivery policy reforms, and how they impact patient activation and empowerment. Such policies include Accountable Care Organizations and Value Based Purchasing, Patient Centered Medical Homes, and the Community Health Benefit. Challenges and possible solutions to implementing the P-PAE are discussed. Comprehensive and longitudinal data sets with consistent P-PAE measures are needed to conduct comparative effectiveness analyses to evaluate the optimal P-PAE model. We believe the P-PAE model is timely and sustainable, and will be critical to engaging patients in their treatment, developing patients’ abilities to manage their health, helping patients to express concerns and preferences regarding treatment, empowering patients to ask questions about treatment options, and building up strategic patient-provider partnerships through shared decision making. PMID:25845376

  15. Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis

    PubMed Central

    Strand, Vibeke; van Vollenhoven, Ronald F.; Lee, Eun Bong; Fleischmann, Roy; Zwillich, Samuel H.; Gruben, David; Koncz, Tamas; Wilkinson, Bethanie

    2016-01-01

    Objective. To evaluate effects of tofacitinib or adalimumab on patient-reported outcomes (PROs) in patients with moderate to severe RA and inadequate responses to MTX. Methods. In this 12-month, phase 3, randomized controlled trial (ORAL Standard), patients (n = 717) receiving background MTX were randomized to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks or placebo. PROs included HAQ-Disability Index, Patient Global Assessment of Arthritis, Patient Assessment of Arthritis Pain, health-related quality of life (Short Form-36 [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) and sleep (Medical Outcomes Study-Sleep). Results. At month 3, tofacitinib 10 mg BID treatment resulted in significant changes from baseline vs placebo across all PROs, sustained to month 12, with the highest number of patients reporting improvements ⩾minimum clinically important differences vs placebo (P < 0.05). Changes from baseline at month 3 with tofacitinib 5 mg BID and adalimumab were similar and statistically significant vs placebo across most PROs, excluding SF-36 Mental Component Score and Social Functioning, Role Emotional, and Mental Health domains, with significantly more patients reporting improvements ⩾minimum clinically important differences. Numbers Needed to Treat were lowest for tofacitinib 10 mg BID and similar between tofacitinib 5 mg BID and adalimumab. Conclusion. Patients with moderate to severe RA and inadequate responses to MTX reported improvements across a broad range of PROs with tofacitinib 5 and 10 mg BID and adalimumab that were significantly superior to placebo. PMID:26929445

  16. Routine use of Zenit RA, a novel chemiluminescent immunoanalyzer in autoimmune disease diagnosis.

    PubMed

    Ghillani, P; Dufat, L; Himeur, S; Miyara, M; Amoura, Z; Musset, L

    2012-04-01

    The detection of antibodies is useful to diagnose and/or to classify autoimmune diseases as connective tissue diseases and vasculitis. Zenit RA is a fully automated immunoanalyzer. The aim of this study was to compare the predictive and discriminative performance of the Zenit RA anti-cyclic citrullinated peptide (CCP), anti-cardiolipin (aCL) and anti-β 2 glycoprotein 1 (aB2GP1) tests to conventional ELISAs on clinically well-defined groups of patients and to daily evaluate the determination of anti-extractable nuclear antigen (ENA), anti-double stranded DNA (dsDNA), anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) antibodies in a hospital laboratory. Reagents available on Zenit RA analyzer exhibit good diagnostic performances, regarding sensitivity, specificity, positive and negative predictive values. Global agreements between Zenit RA and conventional tests were from 90 to 98 % (Kappa-values ranging 0.56-0.94): 96 % for anti-CCP, 90-94 % for aCL and aB2GP1, 94 % for anti-dsDNA, 97 % for anti-ENA, 98 % for anti-MPO and 95 % for anti-PR3 antibodies. Zenit RA analyzer is easy to rapidly detect the most common autoantibodies in autoimmune diseases. This system has a potential to provide clinically useful data within a short time. Because of the flexibility of its work modalities, it is well adapted to determine antigenic specificities in daily practice. PMID:26000125

  17. IL-1RA +2018 polymorphism and the susceptivity to pneumoconiosis: a Meta-analysis

    PubMed Central

    Zhou, Yan; Kang, Yan; Zhang, Zhongwei; Liu, Jin

    2014-01-01

    Background and objectives: It has been reported that host genetic factors may play a crucial role in pneumoconiosis susceptibility. The present study aimed to study the association between IL-1RA +2018 polymorphism and pneumoconiosis by Meta-analysis. Materials and methods: Literatures addressing the association between IL-1RA gene polymorphisms and pneumoconiosis were selected from the PubMed, Cochrane Library, EMBASE, CNKI and Wanfang databases. Statistical analyses were performed by Review Manager Software 5.0.24 and STATA 11.0 software. Results: 5 case-control studies with a total of 609 pneumoconiosis patients and 579 controls were retrieved. Meta-analysis results showed significant association between IL-1RA +2018 polymorphism and pneumoconiosis risk. The C allele carriers have increased risk compared with the T allele carriers (OR=1.68, 95% CI: 1.25-2.27, P=0.0007). Individuals who carry TC or CC genotype have higher risk than those with TT homozygote (OR=1.79, 95% CI: 1.18, 2.71, P=0.006). In subgroup analysis by pneumoconiosis type, a significant association between IL-1RA +2018 polymorphism and pneumoconiosis risk were found in silicosis (C vs T: OR=2.12, 95% CI: 1.63-2.76, P=0.000; TC+CC vs TT: OR=1.79, 95% CI: 1.18-2.71, P=0.006) but not in coal workers’ pneumoconiosis. Conclusion: This Meta-analysis suggests that IL-1RA +2018 polymorphism might be risk factors for pneumoconiosis, especially in silicosis. PMID:25232408

  18. 78 FR 79079 - Agency Information Collection (Dental Patient Satisfaction Survey); Activities under OMB Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... AFFAIRS Agency Information Collection (Dental Patient Satisfaction Survey); Activities under OMB Review... . Please refer to ``OMB Control No. 2900- 0764 (Dental Patient Satisfaction Survey)'' in any correspondence....gov . Please refer to ``OMB Control No. 2900-0764 (Dental Patient Satisfaction Survey)'' in...

  19. Are There Gender-Specific Risk Factors for Suicidal Activity among Patients with Schizophrenia and Depression?

    ERIC Educational Resources Information Center

    Kaplan, Kalman J.; Harrow, Martin; Faull, Robert N.

    2012-01-01

    Are there gender-specific risk factors for suicidal activity among patients with schizophrenia and depression? A total of 74 schizophrenia patients (51 men, 23 women) and 77 unipolar nonpsychotic depressed patients (26 men, 51 women) from the Chicago Follow-up Study were studied prospectively at 2 years posthospitalization and again at 7.5 years.…

  20. 75 FR 16912 - Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    ... AFFAIRS Proposed Information Collection (Dental Patient Satisfaction Survey) Activity: Comment Request... measure patients' satisfaction with VA's dental services. DATES: Written comments and recommendations on..., Dental Patient Satisfaction Survey, VA Form 10-0503. OMB Control Number: 2900-New (VA Form 10-0503)....

  1. Clinicians' and Patients' Assessment of Activity Overuse and Underuse and Its Relation to Physical Capacity

    ERIC Educational Resources Information Center

    de Jong, Annemieke Bonny; Preuper, Henrica R. Schiphorst; Reneman, Michiel F.

    2012-01-01

    To explore clinicians' and patients' (self)-assessment of activity overuse and underuse, and its relationship with physical capacity in patients with chronic musculoskeletal pain (CMP). Study design was cross-sectional. Participants included patients with CMP, admitted to a multidisciplinary outpatient pain rehabilitation program. The main…

  2. Periodontitis and Porphyromonas gingivalis in Preclinical Stage of Arthritis Patients

    PubMed Central

    Hashimoto, Motomu; Yamazaki, Toru; Hamaguchi, Masahide; Morimoto, Takeshi; Yamori, Masashi; Asai, Keita; Isobe, Yu; Furu, Moritoshi; Ito, Hiromu; Fujii, Takao; Terao, Chikashi; Mori, Masato; Matsuo, Takashi; Yoshitomi, Hiroyuki; Yamamoto, Keiichi; Yamamoto, Wataru; Bessho, Kazuhisa; Mimori, Tsuneyo

    2015-01-01

    Purpose To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. Methods We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. Results Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). Conclusion In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA. PMID:25849461

  3. Tuberculosis infection in rheumatic patients with infliximab therapy: experience with 157 patients.

    PubMed

    Nobre, Christiane Aguiar; Callado, Maria Roseli Monteiro; Lima, José Rubens Costa; Gomes, Kirla Wagner Poti; Martiniano, Germana Vasconcelos Mesquita; Vieira, Walber Pinto

    2012-09-01

    It is recommended to evaluate the presence of latent tuberculosis infection (LTBI) prior to the use of antitumor necrosis factor α. The aim of this study is to assess the presence of LTBI in patients with rheumatic diseases undergoing treatment with infliximab in an endemic area for tuberculosis (TB). LTBI was searched through the contact history, chest X-ray and tuberculin skin test with purified protein derivative (PPD) ≥5 mm. We studied 157 patients in the period from May 2005 to October 2008, 99 (63.1%) were women with average age of 49 years and 58 (36.9%) were men with average age of 41 years. The group comprising 90 patients (57.3%) with rheumatoid arthritis (RA), 54 (34.4%) with ankylosing spondylitis (AS) and 13 (8.3%) with psoriatic arthritis (PsA) had PPD reactor 13.4% (21/157), being prevented by isoniazid (INH) in these patients. There are dissimilar responsiveness to the PPD between the three pathologies, and the reactivity was lower in RA (RA × AS: χ(2) = 12; P = 0.0004; and RA × PsA: χ(2) with Yates' correction = 3.6; P = 0.05). No significant difference between the reactivity of the PPD and the use of immunosuppressive drugs (P = 0.81) is observed. The immunoprophylaxis with INH showed an efficacy of 95% (20/21); three (1.9%) patients developed active TB (spondylodiscitis, meningitis and lymphadenopathy) after the use of infliximab, reaffirming extrapulmonary involvement. These results suggest that PPD has a low sensitivity for detection of LTBI in RA and that the previous use of immunosuppressive drugs does not affect the response to PPD. PMID:21822912

  4. Vegetation composition and ²²⁶Ra uptake by native plant species at a uranium mill tailings impoundment in South China.

    PubMed

    Hu, Nan; Ding, Dexin; Li, Guangyue; Zheng, Jifang; Li, Le; Zhao, Weichao; Wang, Yongdong

    2014-03-01

    A field investigation was conducted for the vegetation composition and (226)Ra uptake by native plant species at a uranium mill tailings impoundment in South China. 80 species belonging to 67 genera in 32 families were recorded in the sampling sites. The Poaceae and Asteraceae were the dominant families colonizing the impoundment. The number of the plant species and vegetation community composition in the sampling sites seemed most closely related to the activities of (226)Ra and the pH value of the uranium tailings. The plant species in the sampling sites with relatively low activities of (226)Ra and relatively high pH value formed a relatively stable vegetation community. The plant species in the sampling sites with medium activities of (226)Ra and medium pH value formed the transitional vegetation community. The plant species in the sampling sites with relatively high activities of (226)Ra and relatively low pH value formed a simple unstable vegetation community that was similar to that on the unused grassland. The activities of (226)Ra and transfer factors (TFs) varied greatly with the plant species. The high activities of (226)Ra and TFs were found in the leaves of Pteris multifida (150.6 Bq/g of AW; 9.131), Pteridium aquilinum (122.2 Bq/g of AW; 7.409), and Dryopteris scottii (105.7 Bq/g of AW; 6.408). They satisfied the criteria for a hyperaccumulator for (226)Ra. They may be the candidates for phytoremediation of (226)Ra in the uranium mill tailings impoundment areas and the contaminated soils around. PMID:24412774

  5. [Measurement of physical activity in patients with chronic obstructive pulmonary disease].

    PubMed

    Magnussen, Helgo; Waschki, Benjamin; Watz, Henrik

    2009-04-15

    Physical activity is an important parameter related to morbidity and mortality in cardiovascular disease, metabolic syndrome/diabetes, mental disorders, cancer, and chronic obstructive pulmonary disease (COPD). In COPD, lower levels of physical activity as reported by the patients are associated with a faster annual lung function decline, increased number of hospitalizations, and higher risk of mortality. Self-reported physical activity, however, correlates only poorly with objectively quantified physical activity in patients with COPD. Recent data show that physical activity can reliably be measured in a substantial number of patients with COPD. Extrapulmonary effects of COPD are associated with reduced physical activity. Clinical characteristics commonly used to assess disease severity like the forced expiratory volume in 1 s or the 6-min walk distance only incompletely reflect the physical activity of patients with COPD. PMID:19399389

  6. Are patient questionnaire scores as "scientific" as laboratory tests for rheumatology clinical care?

    PubMed

    Pincus, Theodore

    2010-01-01

    Modern medical care is based largely on laboratory advances, such as microbiological cultures giving rise to antibiotics and hemoglobin A1c leading to "tight control" of diabetes, among many others. Development of a "gold standard" laboratory test has appeared attractive for care of patients with rheumatoid arthritis (RA) since rheumatoid factor was identified in the 1940s. Indeed, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are abnormal in most RA patients. However, each of these tests is normal in at least 30% of patients, and no laboratory test (or any other measure) can serve as a single "gold standard" measure for all individual RA patients. A new approach to quantitative assessment in rheumatic diseases involves patient self-report questionnaires as standardized, quantitative, cost-effective "scientific" data from a medical history, the primary source of RA management decisions. Patient questionnaires distinguish active from control treatments in RA clinical trials at levels similar to laboratory tests (or formal joint counts), and are far more significant in the prognosis of work disability, costs, and premature death than laboratory tests or radiographic scores. RAPID3 (routine assessment of patient index data) on an MDHAQ (multidimensional health assessment questionnaire) requires 5 seconds to score, compared to 114 seconds for a DAS28 (disease activity score). Patient questionnaires do not replace further medical history, physical examination, laboratory or other tests, and require physician interpretation for patient management, as do laboratory tests and all quantitative data. Advances in therapy require laboratory science, but patient questionnaires provide optimal "scientific" data for clinical care. PMID:20632989

  7. Validity of a Questionnaire to Assess the Physical Activity Level in Coronary Artery Disease Patients

    ERIC Educational Resources Information Center

    Guiraud, Thibaut; Granger, Richard; Bousquet, Marc; Gremeaux, Vincent

    2012-01-01

    The aim of the study is to compare, in coronary artery disease patients, physical activity (PA) assessed with the Dijon Physical Activity Questionnaire (DPAQ) and the true PA objectively measured using an accelerometer. Seventy patients wore an accelerometer (MyWellness Key actimeter) throughout 1 week after a cardiac rehabilitation program that…

  8. Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA.

    PubMed

    Rochette-Egly, Cécile

    2015-01-01

    Retinoic acid (RA), the active derivative of vitamin A, a fat-soluble vitamin, plays key roles in cell growth and differentiation by activating nuclear receptors, RARs (α, β and γ), which are ligand dependent regulators of transcription. The past years highlighted several novelties in the field that increased the complexity of RA effects. Indeed, in addition to its classical genomic effects, RA also has extranuclear and non-transcriptional effects. RA induces the rapid and transient activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of RARs at a conserved serine residue located in the N-terminal domain and their coregulators. In order to investigate the relevance of RARs' phosphorylation in cell differentiation, mouse embryonic stem (mES) cells were used as a model. When treated with RA, these pluripotent cells give rise to neuronal cells. Cells invalidated for each RAR were generated as well as stable rescue lines expressing RARs mutated in phosphor acceptor sites. Such a strategy revealed that RA-induced neuronal differentiation involves the RARγ2 subtype and requires RARγ2 phosphorylation. Moreover, in gene expression profiling experiments, the phosphorylated form of RARγ2 was found to regulate a small subset of genes through binding a novel RA response element consisting of two direct repeats with a 7 base pair spacer. These new findings suggest an important role for RAR phosphorylation during cell differentiation, and pave the way for further investigations with other cell types and during embryonic development. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. PMID:24768681

  9. The influence of lifestyle habits on quality of life in patients with established rheumatoid arthritis—A constant balancing between ideality and reality

    PubMed Central

    Malm, Karina; Bremander, Ann; Arvidsson, Barbro; Andersson, Maria L. E.; Bergman, Stefan; Larsson, Ingrid

    2016-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic disease with symptoms that limit activities and affect quality of life. RA is associated with an increased risk of developing comorbidities, some of which are also known to be associated with lifestyle habits such as physical activity, diet, smoking, and alcohol. There has been an augmented focus on the implementation and maintenance of healthy lifestyle habits even for patients with RA in the past decade, but little is known about the link between patients’ experiences of lifestyle habits and quality of life. The aim of the study was thus to describe and explore how patients with established RA experience the influence of lifestyle habits on quality of life. Methods The study had a descriptive and explorative design, based on qualitative content analysis. Strategic sampling was used in order to achieve variations in experiences. Twenty-two patients with RA (14 women and 8 men) from 30 to 84 years old, with a disease duration ranging from 8 to 23 years, were interviewed. Results The analysis of the influence of lifestyle habits on quality of life resulted in the theme balancing between ideality and reality. Three categories emerged about how lifestyle habits influenced quality of life by limitations (including insufficiency and adaptation), self-regulation (including guilt and motivation), and companionship (including belonging and pleasure). Conclusions Quality of life for patients with established RA was influenced by the balance between ideality and reality in the lifestyle habits: physical activity, diet, smoking, and alcohol. This is important new knowledge for health professionals when discussing lifestyle habits with RA patients. PMID:27172513

  10. Association of the polymorphisms of TRAF1 (rs10818488) and TNFAIP3 (rs2230926) with rheumatoid arthritis and systemic lupus erythematosus and their relationship to disease activity among Egyptian patients

    PubMed Central

    Mohannad, Nevine

    2016-01-01

    Aim of the study Recent studies demonstrated the association of tumor necrosis factor α-induced protein 3 (TNFAIP3) (rs2230926) and tumor necrosis factor receptor associated factor 1 (TRAF1) (rs10818488) with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in different populations. We aimed at determining whether they confer susceptibility to SLE and RA in Egyptian population and if there is any relation to disease activity and auto-antibodies profile. Material and methods A case-control study involving 105 individuals with RA, 90 with SLE and 75 healthy controls was performed using TaqMan genotyping assay for two SNPs that showed the best evidence of association in the previous Caucasian studies. Results We detected significant differences in G allele frequency of TNFAIP3 (rs2230926) with SLE (p = 0.017*) and RA (OR = 2.333; 95% CI: 1.103-4.935, p = 0.023*) and association with RA disease activity (< 0.001). The A allele of TRAF1 was significantly increased in RA compared to controls(p = 0.049) and with RA activity (p = 0.001), while TRAF1 polymorphism did not exhibit any significant difference in the frequencies of genotypes or alleles in SLE and control (p = 0.280). Conclusions TNFAIP3 is a susceptibility gene to SLE and RA in the Egyptian population and is correlated to disease activity and the presence of autoantibodies while TRAF1 polymorphisms increase the risk of RA but not to SLE in Egyptian populations. PMID:27536202

  11. Type 2 diabetes and dog walking: patients' longitudinal perspectives about implementing and sustaining physical activity

    PubMed Central

    Peel, Elizabeth; Douglas, Margaret; Parry, Odette; Lawton, Julia

    2010-01-01

    Background Physical activity is particularly important for people with type 2 diabetes, as evidence suggests that any reduction in sedentary time is good for metabolic health. Aim To explore type 2 diabetes patients' talk about implementing and sustaining physical activity. Design of study Longitudinal, qualitative study using repeat in-depth interviews with 20 patients over 4 years following clinical diagnosis. Setting Patients were recruited from 16 general practices and three hospitals across Lothian, Scotland. Results Discussion, and salience, of physical activity was marginal in patient accounts of their diabetes management. Patients claimed to have only received vague and non-specific guidance about physical activity from health professionals, and emphasised a perceived lack of interest and encouragement. Aside from walking, physical activities which were adopted tended to attenuate over time. Patients' accounts revealed how walking a dog assisted this kind of activity maintenance over time. Three main themes are highlighted in the analysis: 1) incidental walking; 2) incremental physical activity gains; and 3) augmenting physical activity maintenance. The problems arising from walking without a dog (for example, lack of motivation) are also examined. Conclusion Asking patients about pet preferences might seem tangential to medical interactions. However, encouraging dog walking or identifying another interest that promotes a regular commitment to undertake physical activity may yield long-term health benefits. PMID:20822690

  12. Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

    SciTech Connect

    Jacobs, M.P.; Baughman, R.P.; Hughes, J.; Fernandez-Ulloa, M.

    1985-05-01

    Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (including 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).

  13. Signaling pathway models as biomarkers: Patient-specific simulations of JNK activity predict the survival of neuroblastoma patients.

    PubMed

    Fey, Dirk; Halasz, Melinda; Dreidax, Daniel; Kennedy, Sean P; Hastings, Jordan F; Rauch, Nora; Munoz, Amaya Garcia; Pilkington, Ruth; Fischer, Matthias; Westermann, Frank; Kolch, Walter; Kholodenko, Boris N; Croucher, David R

    2015-12-22

    Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characterized the network that regulated stress signaling by the c-Jun N-terminal kinase (JNK) pathway in neuroblastoma cells. We generated an experimentally calibrated and validated computational model of this network and used the model to extract prognostic information from neuroblastoma patient-specific simulations of JNK activation. Switch-like JNK activation mediates cell death by apoptosis. An inability to initiate switch-like JNK activation in the simulations was significantly associated with poor overall survival for patients with neuroblastoma with or without MYCN amplification, indicating that patient-specific simulations of JNK activation could stratify patients. Furthermore, our analysis demonstrated that extracting information about a signaling pathway to develop a prognostically useful model requires understanding of not only components and disease-associated changes in the abundance or activity of the components but also how those changes affect pathway dynamics. PMID:26696630

  14. Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporal kinase activation states during differentiation

    PubMed Central

    Park, Keon-Young; Li, Weiwei A.; Platt, Manu O.

    2012-01-01

    Patient-to-patient variability in disease progression continues to complicate clinical decisions of treatment regimens for cardiovascular diseases, metastatic cancers and osteoporosis. Here, we investigated if monocytes, circulating white blood cells that enter tissues and contribute to disease progression by differentiating into macrophages or osteoclasts, could be useful in understanding this variability. Monocyte-derived macrophages and osteoclasts produce cysteine cathepsins, powerful extracellular matrix proteases which have been mechanistically linked to accelerated atherosclerotic, osteoporotic, and tumor progression. We hypothesized that multivariate analysis of temporal kinase activation states during monocyte differentiation could predict cathepsin proteolytic responses of monocyte-derived macrophages and osteoclasts in a patient-specific manner. Freshly isolated primary monocytes were differentiated with M-CSF or RANKL into macrophages or osteoclasts, respectively, and phosphorylation of ERK1/2, Akt, p38 MAPK, JNK, c-jun, and IκB-α were measured at days 1, 3, 6, and 9. In parallel, cell diameters and numbers of nuclei were measured, and multiplex cathepsin zymography was used to quantify cathepsins K, L, S, and V activity from cell extracts and conditioned media. There was extensive patient-to-patient variability in temporal kinase activation states, cell morphologies, and cathepsin K, L, S, and V proteolytic activity. Partial least squares regression models trained with temporal kinase activation states successfully predicted patient-specific morphological characteristics (mean cell diameter and number of nuclei) and patient-specific cathepsin proteolytic activity with predictability as high as 95%, even with the challenge of incorporating the complex, unknown cues from individual patients’ unique genetic and biochemical backgrounds. This personalized medicine approach considers patient variability in kinase signals to predict cathepsin activity

  15. The relative mobility of U, Th and Ra isotopes in the weathered zones of the Eye-Dashwa Lakes granite pluton, northwestern Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Latham, A. G.; Schwarcz, H. P.

    1987-10-01

    Radioisotope activity ratios of weathered surface rocks from the Eye-Dashwa Lakes granite pluton show that, in the 238U decay series, 226Ra has been leached more rapidly than the grandparent 234U and 238U isotopes. The observation of 238Th /232Th disequilibria in the 232Th decay series shows that either 228Th (half-life of 1.9 yrs) or 228Ra (half-life of 5.75 yrs) have been removed from these rocks very rapidly indeed. Isotope ratios of separated mineral fractions appear to show that whereas uranium tends to be removed from all mineral fractions, Ra is strongly readsorbed onto feldspars, presumably as these undergo alteration to clay minerals. This necessitates making a distinction between intermineral mobility of U or Ra, and the net loss of U or Ra from the whole rock. An attempt has been made to model, quantitatively, the transport rate of Ra, though with little success. Failure of the modelling appears to indicate that the mobility of 228Ra is higher than might be predicted by the mobility of 226Ra; that is, the two isotopes are not strict analogues of one another in their response to initial weathering.

  16. Leaching of 226Ra from components of uranium mill tailings

    USGS Publications Warehouse

    Landa, E.R.

    1991-01-01

    A sequential extraction procedure was used to characterize the geochemical forms of 226Ra retained by mixtures of quartz sand and a variety of fine-grained rock and mineral species. These mixtures had previously been exposed to the sulfuric acid milling liquor of a simulated acid-leach uranium milling circuit. For most test cases, the major fraction of the 226Ra was extracted with 1 mol/1 NH4Cl and was deemed to be exchangeable. However, 226Ra retained by the barite-containing mixture was resistant to both 1 mol/1 NH4Cl and 1 mol/HCHCl extraction. ?? 1991.

  17. Progress toward an EDM measurement in {sup225}Ra.

    SciTech Connect

    Holt, R. J.; Ahmad, I.; Bailey, K.; Graner, B.; Greene, J. P.; Korsch, W.; Lu, Z.-T.; Mueller, P.; O'Connor, T. P.; Sulai, I. A.; Trimble, W. L.

    2010-11-01

    Permanent electric dipole moments (EDMs) in atoms or molecules are a signature of time-reversal and parity violation and represent an important window onto physics beyond the Standard Model. We are developing a next generation EDM search based on laser-cooled and trapped {sup 225}Ra atoms. Due to octupole deformation of the nucleus, {sup 225}Ra is predicted to be two to three orders of magnitude more sensitive to T-violating interactions than {sup 199}Hg, which currently sets the most stringent limits in the nuclear sector. We will discuss progress toward realizing a first EDM measurement for {sup 225}Ra.

  18. Concurrent determination of 224Ra, 226Ra, 228Ra, and unsupported 212Pb in a single analysis for drinking water and wastewater: dissolved and suspended fractions.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail

    2004-02-01

    A technique has been developed for the measurement of 224Ra, 226Ra, 228Ra, and unsupported 2t2Pb concurrently in a single analysis. The procedure can be applied to both drinking water and wastewater, including the dissolved and suspended fractions of a sample. For drinking water samples, using 3-L aliquots, the radium isotopes are isolated by a fast PbSO4 co-precipitation and then quantified by gamma-ray spectroscopy. The radium isotopes 224Ra, 226Ra, and 228Ra are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb (and/or 214Bi), and 228Ac, respectively. Because of the short half-life of 224Ra (T1/2 = 3.66 d), the precipitate should be counted within 4 d of the sample collection date. In case the measurement of unsupported 212Pb (T1/2 = 10.64 h) is required, the gamma-ray analysis should be initiated as soon as possible, preferably on the same day of collection. The counting is repeated after about 21 d to ensure the 226Ra progeny are in equilibrium with their parent. At this point, the 228Ac equilibration with its 228Ra parent is already established. In the case of samples containing suspended materials, an aliquot of sample is filtered and then the filtrate is treated as described above for drinking water samples. The suspended fraction of sample, collected on the filter, is directly analyzed by gamma-ray spectroscopy with no further chemical separation. Aliquots of de-ionized water spiked with various radium standards were analyzed to check the accuracy and precision of the method. In addition, analysis results of actual samples using this method were compared with the ones performed using U.S. Environmental Protection Agency-approved procedures, and the measured values were in close agreement. This method simplifies the analytical procedures and reduces the labor while achieving the precision, accuracy, and minimum detection concentration requirements of EPA's Regulations. PMID:14744047

  19. Repeated activation of mania by atypical antipsychotics in a patient

    PubMed Central

    Raghunath, Ashwati

    2012-01-01

    A 50-year-old, white female patient was diagnosed with schizophrenia in her teens. Her illness did not respond adequately to treatment until she was placed on a combination of fluoxetine and conventional antipsychotics. She discontinued the conventional antipsychotics on a number of occasions, which caused her to become psychotic, but not manic. On two separate occasions she was placed on atypical antipsychotics that were associated with the occurrence of manic symptoms. Once the patient was restarted on conventional antipsychotics, she remained stable. PMID:23188864

  20. Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in systemic mastocytosis and rheumatoid arthritis.

    PubMed

    Cho, Catherine; Nguyen, Anna; Bryant, Katherine J; O'Neill, Sean G; McNeil, H Patrick

    2016-03-01

    Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity. A prospective, cross-sectional cohort study was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM. Urine samples were collected from patients with RA (n = 60), SM (n = 17) and healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing elevated levels. One third of patients with RA had elevated T-PGDM excretion, and the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo MC activity and elevated levels in 33% of patients with RA provides evidence of MC activation in this disease. PMID:27042302

  1. 6-Formylindolo(3,2-b)Carbazole (FICZ) Modulates the Signalsome Responsible for RA-Induced Differentiation of HL-60 Myeloblastic Leukemia Cells

    PubMed Central

    Bunaciu, Rodica P.; LaTocha, Dorian H.; Varner, Jeffrey D.; Yen, Andrew

    2015-01-01

    6-Formylindolo(3,2-b)carbazole (FICZ) is a photoproduct of tryptophan and an endogenous high affinity ligand for aryl hydrocarbon receptor (AhR). It was previously reported that, in patient-derived HL-60 myeloblastic leukemia cells, retinoic acid (RA)-induced differentiation is driven by a signalsome containing c-Cbl and AhR. FICZ enhances RA-induced differentiation, assessed by expression of the membrane differentiation markers CD38 and CD11b, cell cycle arrest and the functional differentiation marker, inducible oxidative metabolism. Moreover, FICZ augments the expression of a number of the members of the RA-induced signalsome, such as c-Cbl, Vav1, Slp76, PI3K, and the Src family kinases Fgr and Lyn. Pursuing the molecular signaling responsible for RA-induced differentiation, we characterized, using FRET and clustering analysis, associations of key molecules thought to drive differentiation. Here we report that, assayed by FRET, AhR interacts with c-Cbl upon FICZ plus RA-induced differentiation, whereas AhR constitutively interacts with Cbl-b. Moreover, correlation analysis based on the flow cytometric assessment of differentiation markers and western blot detection of signaling factors reveal that Cbl-b, p-p38α and pT390-GSK3β, are not correlated with other known RA-induced signaling components or with a phenotypic outcome. We note that FICZ plus RA elicited signaling responses that were not typical of RA alone, but may represent alternative differentiation-driving pathways. In clusters of signaling molecules seminal to cell differentiation, FICZ co-administered with RA augments type and intensity of the dynamic changes induced by RA. Our data suggest relevance for FICZ in differentiation-induction therapy. The mechanism of action includes modulation of a SFK and MAPK centered signalsome and c-Cbl-AhR association. PMID:26287494

  2. Use of Virtual Patients in an Advanced Therapeutics Pharmacy Course to Promote Active, Patient-Centered Learning

    PubMed Central

    Mohammad, Rima A.; Benedict, Neal

    2014-01-01

    Objective. To assess student satisfaction and learning of course objectives following the integration of virtual patient cases designed to promote active, patient-centered learning in an advanced therapeutics pharmacy course. Design. A dynamic virtual patient platform that incorporated a branched-narrative, decision-making teaching model was used in an advanced therapeutics course to supplement lecture content. Assessment. Presimulation and postsimulation tests were used to assess student learning. The use of virtual patients significantly enhanced student learning for both higher- and lower-level test questions (p<0.001 and p=0.01, respectively). Students agreed or strongly agreed that the virtual patient cases provided an effective way to learn (72%), were enjoyable (69%), and were appropriate in content (80%), and that more should be incorporated (59%). Conclusion. The use of virtual patients in an advanced therapeutics practicum effectively promoted active, patient-centered learning; engaged students in an interactive and dynamic educational technology; encouraged teamwork; enhanced higher-level student learning; and improved student satisfaction in the course. PMID:25147397

  3. Patient Mood and Instrumental Activities of Daily Living in Alzheimer Disease: Relationship Between Patient and Caregiver Reports.

    PubMed

    Votruba, Kristen L; Persad, Carol; Giordani, Bruno

    2015-09-01

    This retrospective study investigated the relationship between self-reports and caregiver perceptions of patients' depressive symptoms and the respective ability of these reports to predict instrumental activities of daily living (IADLs) beyond what is accounted for by cognitive abilities in 71 patients with mild Alzheimer disease. Patients completed the Geriatric Depression Scale-Short Form, and caregivers completed the Behavior Rating Scale for Dementia assessing their perception of patients' depressive symptoms. Caregivers also completed IADL items from the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory. Cognitive measures included the Mini-Mental State Examination, Logical Memory from the Wechsler Memory Scale III, and Trail Making Test, Part B. The relationship between self-reported depressive symptoms and caregiver report of patients' depressive symptoms showed a trend toward significance (r = .22, P = .06). Measures of depressive symptoms significantly predicted 12.5% of the variance in IADLs performance, beyond that accounted for by patient demographics and cognitive functioning. Interestingly, patients' reports, rather than caregivers', were particularly useful in this prediction. PMID:260