tbuckley/cabot-search huggingface dataset:
AB0402 Concomitant medication frequency and profiles in a real-life canadian cohort of RA patients treated with infliximab
Authors: M. Khraishi, D. Choquette, E. Rampakakis, J. Sampalis, S. Otawa, S. Khalil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The use of concomitant medications, related to rheumatoid arthritis (RA) or to other chronic conditions, is frequent in RA patients. The purpose of this analysis is to determine the frequency and profiles of concomitant medications used in a routine clinical practice setting and to assess the impact of infliximab (IFX) treatment. <h3>Methods</h3> The data for this analysis were obtained from BioTRAC, an observational prospective registry of adult RA patients initiated on treatment with Infliximab since 2002 and managed as per routine care. Patients enrolled were biologic-naïve or had initiated treatment with a biologic for a period of &lt;6 months prior to enrolment. Analyses for RA-related medications was performed on the overall cohort (N=775). Since, non-RA related medications started being collected since 2007, a subgroup analysis was also performed in the 272 patients enrolled since then. <h3>Results</h3> In the overall cohort, mean (SD) age was 55.9 (13.5) years, mean (SD) disease duration 10.3 (10.0) years. At baseline, the prevalence of RA-related concomitant medications was 90.1%, 56.0%, 39.6% and 19.9% for DMARDs, NSAIDS, corticosteroids and narcotic analgesics, respectively. Patients with higher disease duration and disease activity (CDAI) at baseline were being treated with an increased number of RA medications (P&lt;0.001) and DMARDs (P&lt;0.001) at baseline. Treatment with IFX for 12 months reduced the mean number of RA medications between baseline and 12 months (P&lt;0.001). In the sub-group analysis, the baseline characteristics did not differ between patients with or without comorbidity-associated medications. The prevalence of medications associated with comorbidities was 31%. The most common comorbidity-associated medication was for anxiety/depression (17.6%), hypertension (7.0%), gastric disorders (6.3%), dyslipidemia (5.5%), and bone disorders (5.5%). The presence of comorbidities had no impact on the DAS-28 response following IFX treatment or the utilization of RA medication. However, patients with comorbidities experienced a higher number of non-serious adverse events (NSAEs) compared to patients without comorbidities (320.7 vs. 146.3 NSAEs/100 patient years (PY), respectively). The incidence of serious AEs (SAEs) was comparable between the two groups (6.4 vs. 6.4 SAEs/100 PY in patients with vs. without comorbidities). <h3>Conclusions</h3> The results of this real-life observational study demonstrate that disease activity and duration seem to be associated with increased use of RA medications. Treatment with IFX slightly decreases the number of RA medications over time. NSAEs were reported by a greater number of patients with comorbidities compared to patients without comorbidities, however, the incidence of SAEs was comparable between the groups. <h3>Disclosure of Interest</h3> None Declared
AB0282 Increased prescription of tumour necrosis factor alpha antagonists is strongly associated with a reduction in myocardial infarctions in rheumatoid arthritis patients based on a 16 year analysis of nationwide data.
Authors: P. A. MacMullan, L. C. Harty, O. Fitzgerald
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) die prematurely from cardiovascular disease (CVD) with persistent inflammation likely playing an important role in the development of atherosclerosis. Conversely, induction of remission reduces CVD risk in RA. Methotrexate (MTX) monotherapy induces remission in 20% of RA patients v 55-80% remission with Tumour Necrosis Factor inhibitors (TNFi) and MTX combination therapy. <h3>Objectives</h3> (1) To evaluate the number of Myocardial Infarctions (MI) in RA patients discharged from hospital from 1995 to 2010; and (2) to assess any association with therapy, including TNFi usage. <h3>Methods</h3> The Hospital In-Patient Enquiry system (HIPE), a national system recording information on hospital bed utilization, was evaluated from 57 hospitals from 1995-2010 for patients admitted with a diagnosis of RA. Age group, number of inpatient days, gender and reason for admission (ICD codes) were also recorded. Annual prescription data for TNFi usage nationally was separately analysed from 2000 to 2010. Descriptive analyses are presented as totals, mean (standard deviation (SD)) and mean % change. Correlations were examined by Spearman's rho; p&lt;0.05 was considered statistically significant. <h3>Results</h3> 57,774 inpatient records in RA patients were reviewed from 1995-2010; F: M 2:1, mean age 66 (16). A total of 807 RA patients were discharged following admission for MI in this time period; F:M 1.4:1, mean age 71 (10). 53 per annum (pa) MI's in RA were recorded from 1995-2000, increasing to 77pa up to 2004, with a subsequent 8%pa reduction to 2010 when 29 were recorded, reflecting a total 62% reduction in the annual incidence of MI's in RA. At a national level, the total number of MI's discharged pa increased from 6492 in 2000 to 8052 in 2010. The incidence ratio of MI's in RA to total MI's nationally decreased by 66% from 0.012 to 0.004 in this same period. Annual TNFi prescribing has increased by 156% per annum (pa) from 2389 units in 2000 to 116,747 in 2010. Increased prescription of TNFi negatively correlated with the annual incidence of MI in pt's with RA (r=-0.7, p=0.015). Where information was available nationally (33% population), there was a trebling in the prescription of MTX from 2000-2010. <h3>Conclusions</h3> Increased prescription of TNFi drugs and likely also MTX has coincided with a 62% reduction in the annual incidence of MI's in RA despite escalating national MI rates. Prescription of TNFi drugs strongly negatively correlated with the annual incidence of MI's in RA with a concurrent increase in the prescription of MTX. It is recognised that factors other than TNFi usage, such as better control of traditional CVD risk factors may also have contributed to these improved patient outcomes. <h3>Disclosure of Interest</h3> None Declared
Hepatobiliary Imaging in a Patient With Liver Abscess
Authors: N Bonanno, S Baldari, G Restifo-Pecorella, A Certo, A Versaci, M L Terranova
Journal: Clinical Nuclear Medicine (2000)

Hepatobiliary scintigraphy (HBS) was performed in a patient in whom pyogenic liver abscess developed approximately 1 month after he underwent an interventional radiology procedure to relieve obstructive jaundice caused by an ampullary tumor. HBS, apart from detecting the abscess cavity as a “cold” space-occupying lesion, well demonstrated biliary flow impairment and dilatation of bile ducts, the communication between the abscess cavity and the biliary tree, and the presence of a bile leak. All these findings were disclosed by a single imaging procedure and appeared to be useful for patient management.
AGEING AND DETOXICATION
Authors: KARL STERN, EWART G. HINDS, BRIGITTE A. ASKONAS
Journal: American Journal of Psychiatry (1945)

The detoxifying capacity of the organism during psychoses of the involutional and old age period was investigated by Quick's intravenous hippuric acid test. Seventy-one patients were studied, 48 of whom were 45 years and older; 30 of these were 6o years and older. Evidence of faulty detoxication was present in more than three times the number of patients of 6o years and older, than had been found by previous investigators in mentally normal people of the same age group. Moreover, a small group (5) of cases of senile dementia had conspicuously low values, even when compared with patients of the same age suffering from affective disorders or from hypertensive encephalopathy. A comparison of these cases among themselves shows that gross differences in diet and nutrition, differences in body weight, in blood pressure and in urinary excretion can be neglected as sources of error. The significance of these findings is discussed.
AB0692 What do we know about juvenile idiopathic arthritis and vitamin d? systematic literature review and meta-analysis of current evidence
Authors: M. Nisar, P. Cookson, F. Masood, A. Sansome, A. Ostor
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Over the last decade Vitamin D (Vit D) has been the focus of considerable interest as a potential immunomodulator in a variety of conditions including autoimmune disease. Its influence in juvenile idiopathic arthritis (JIA) however is unclear. We therefore wished to clarify a possible link with the currently available evidence. <h3>Objectives</h3> To establish a link between Vit D insufficieny and JIA <h3>Methods</h3> A systematic literature review was undertaken using Embase, Cochrane and Medline for manuscripts up to May 2011. Search results were then assessed by 2 independent reviewers and relevant articles were further screened by full text review. Only those specifically reporting Vit D levels or its supplementation in JIA (ages between 0-18 years) were selected. Meta-analysis was performed where possible with those papers reporting similar data and analysis techniques. <h3>Results</h3> In total, 19 papers (n=745) were included in the review. Fourteen papers quoted 25(OH)D levels within their study groups with a mean of 24.56 ng/ml (range: 11.5-56.4 ng/ml) in a total of 529 children. Eleven papers quoted 1,25(OH)<sub>2</sub>D levels with a mean of 31.09 pg/ml (range 6.1-65.0 pg/mol) in a total of 518 children. Three studies reporting the prevalence ofVit D deficiency in their cohorts found that up to 82% of children had insufficient levels. Five papers reported Vit D levels by JIA subtype and showed lower levels of both 25(OH)D [mean 15.35, range 8.5 -24.5 ng/ml] and 1,25(OH)<sub>2</sub>D [ mean 22.89, range 5.6-50 pg/ml] in systemic JIA. Four papers reported Vit D supplementation in JIA however the treatment effect was unclear. <h3>Conclusions</h3> At present no clear evidence exists to support a link between Vit D level and JIA. Furthermore the role of Vit D supplementation in the management of JIA is lacking. Despite Vit D levels appearing to be lower in JIA, interpretation is problematic as no agreed definition of Vit D deficiency exists in this population. A need remains therefore to standardise Vit D levels in the paediatric population and in JIA. <h3>Disclosure of Interest</h3> None Declared
Plasma lipid levels in patients with panic disorder or agoraphobia
Authors: C Hayward, C B Taylor, W T Roth, R King, W S Agras
Journal: American Journal of Psychiatry (1989)

Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.
Black Teens Have Low Smoking Rates
Authors: J. Siegfried
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Black Teens Have Low Smoking Rates Get access Juliette Siegfried Juliette Siegfried Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 24, 18 December 1991, Pages 1790–1791, https://doi.org/10.1093/jnci/83.24.1790 Published: 18 December 1991
FRI0454 Uveitis is associated to hypertension and cardiovascular disease in ankylosing spondylitis
Authors: I.J. Berg, A.G. Semb, D. van der Heijde, T.K. Kvien, H. Dagfinrud, S.A. Provan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Uveitis is a common feature of ankylosing spondylitis (AS) affecting approx. 30% of the patients. The literature describing the disease activity and co-morbidities in this subgroup is sparse. <h3>Objectives</h3> To compare disease activity and co-morbidities in AS patients with and without uveitis. <h3>Methods</h3> A cross-sectional study of AS patients recruited from a hospital cohort of AS patients diagnosed according to the mod New York criteria. Frequency of co-morbidities was assessed from questionnaires and interviews, clinical examination was performed, serum markers analyzed and composite measures were used to assess disease activity and function (ASDAS-CRP, BASDAI, BASFI and BASMI). Statistical analyses were performed in SPSS 20 using bivariate test as appropriate. Associations between uveitis and disease activity were analyzed using multiple linear regression models with adjustments for age, gender and use of TNF-inhibitors. Associations between uveitis and co-morbidities were analyzed using logistic regression models with adjustments for age and gender. These models were also adjusted for possible confounders: ASDAS, CRP (in separate models) and smoking habits. <h3>Results</h3> 159 AS patient participated in the study, and as many as 84 (52.8%) had experienced one or more episodes of uveitis. The patients with uveitis were non-significantly older than patients without uveitis (uveitis vs. no uveitis): 52.1 vs. 48.8, p=0.08. There were no significant differences regarding other demographic data (gender, education&gt;12 years, smoking habits) or in the acute phase reactants (ESR, CRP). More patients with uveitis used TNF-inhibitors (25.0 % vs. 10.8%, p=0.02), while there were no significant differences in use of NSAIDS or DMARDS. In adjusted analyses uveitis was associated to higher disease activity and worse function for all measurements, but only statistically significant for BASFI (figure 1). Uveitis was associated to hypertension and atherosclerotic cardiovascular disease (CVD), and the difference remained significant after adjustments for confounders (figure 2) <h3>Image/graph</h3> <h3>Conclusions</h3> We found numerically but non-significant associations between uveitis and disease activity, indicating that presence of uveitis represent a more active disease state. Further we found a significant association, after adjustment for CRP and smoking, between uveitis and atherosclerotic CVD and hypertension indicating that patients with uveitis are at a higher risk of CVD. <h3>Disclosure of Interest</h3> None Declared
Abstract 5247: Human melanoma cells resist oxidative stress due to overactive MEK/ERK and AKT/mTOR pathways and overproduction of melanin.
Authors: David Calianese, Garrett Cammarata, Gabriella Brum, Kevin Szulak, Charles Best, Katelyn Higgins, Yinsheng Wan
Journal: Cancer Research (2013)

Abstract Melanoma is considered as one of the most aggressive and less treatable cancers. While various models of mechanisms have been proposed, the transformation from tranquil melanocytes to invasive melanoma cells remains an enigma. Alteration of cellular redox status has been suggested to be associated with cellular transformation. We compared primary human melanocytes and melanoma cells and their responses to oxidative stress. Both cells were treated with H2O2 at doses between 5 and 250μM. Microscopic data showed that melanoma cells are more resistant to H2O2 treatment. Western blot and confocal microscopic data showed that in melanoma cells, H2O2 does not induce CRT translocation which is considered as a mechanism through which melanocytes surrender to oxidative stress and induces immunogenic cell death. Furthermore, Western blot analysis showed that melanoma cells express EGFR, responsive to EGF treatment and have constitutive activation of AKT and mTOR, which are all related to better survival. In contrast, in the primary human melanocytes, EGFR expression is almost undetectable. And confocal microscopic data confirm this observation. Treatments of cells with MEK/ERK inhibitor U0126 and PI3K/AKT inhibitor LY294002 attenuates S6 phosphorylation. We also observed that in melanoma cells, but not in melanocytes, low dose (5 to 250μM) of H2O2 induces melanin production that is recognized to protect from further oxidative stress. Collectively, our data suggest that active MEK/ERK and AKT/mTOR pathways and up-regulation of melanin production contribute to the resistance of melanoma cells to oxidative stress and attribute to the aggressiveness of melanoma. Our data provides insights into the understanding of the molecular mechanisms of the transformation from melanocytes to melanoma and support the notion from the most recently published proteomic studies that EGFR remains one of the most important targets for better clinical management of melanoma. Citation Format: David Calianese, Garrett Cammarata, Gabriella Brum, Kevin Szulak, Charles Best, Katelyn Higgins, Yinsheng Wan. Human melanoma cells resist oxidative stress due to overactive MEK/ERK and AKT/mTOR pathways and overproduction of melanin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5247. doi:10.1158/1538-7445.AM2013-5247 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
A2.18 Induction and characterisation of the dominant IL-10 producing B cell subset in healthy blood donors and rheumatoid arthritis patients
Authors: ZS Bankó, J Pozsgay, M Tóth, T Gáti, G Nagy, B Rojkovich, G Sármay
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The most important feature of B-cells is the production antibodies upon activation; additionally, B-cells produce both pro-inflammatory and anti-inflammatory cytokines in response to certain stimuli. IL-10 producing B10 cells represent a major subset of regulatory B-cells (Bregs). Bregs suppress autoimmune and inflammatory responses by multiple mechanisms. B-cells play crucial role in the development and maintenance of the chronic inflammatory autoimmune disease, Rheumatoid arthritis (RA); however, controversial data are available on B10 population in RA. Our aim was to identify the optimal conditions inducing B10 cells in samples from healthy controls and RA patients; furthermore, to shed light on signalling pathways resulting in the expansion of the B10 subset. <h3>Materials and methods</h3> Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy donors and RA patients. B cells were purified by magnetic separation, using negative selection. We assessed IL-10 and TNF expressing B-cells after intracellular staining by flow cytometry, and measured the secreted cytokines with multiplex bead array. Phosphorylation of key signalling molecules was monitored by phospho-flow method. <h3>Results</h3> The results show that dual stimulation by CpG and CD40L for 48h was optimal for IL-10 induction, which was synergistically boosted by IL-21. We identified CD19<sup>+</sup> CD27<sup>+</sup> memory B-cells as the major source of B10 cells. IL-21 increased the ratio of BLIMP1 and IL-10 double positive plasmablasts. In RA patients we detected significantly less CD27<sup>+</sup> B10 cells as compared to the controls, while addition of IL-21 to the dual stimuli significantly elevated the number of B10 cells both in the CD19<sup>+</sup>CD27<sup>+</sup> and in the CD19<sup>+</sup> CD27<sup>-</sup> population. Different combinations of stimuli induced preferentially the secretion of pro-inflammatory cytokines (TNF, IFNγ, IL-17) and the suppressor cytokine, IL-10. We assumed that activation of ERK, p38 and CREB are indispensable to induce IL-10, while STAT3 appears to be a co-activator for IL-10 transcription in human Bregs. <h3>Conclusions</h3> CD19<sup>+</sup>CD27<sup>+</sup> memory B-cells are the major source of human B10 cells, which may expand and differentiate to IL-10 producing plasmablasts in the presence of IL-21. CREB and the co-activator STAT3 are the key transcription factors responsible for the expansion of the B10 population. Support: National Research, Development and Innovation Office (OTKA104846), and ELTE TÁMOP 4.2.1./B-09/1/KMR-2010–0003
Abstract 1228: HOXB13 promotes androgen independent growth of prostate cancer cells by the activation of E2F signaling
Authors: Young-Rang Kim, Kyung-Jin Oh, Chan Choi, Min Soo Kim, Taek Won Kang, Chaeyong Jung
Journal: Cancer Research (2010)

Abstract Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1228.
Positive cerebellar feedback loops
Authors: Germund Hesslow
Journal: Behavioral and Brain Sciences (1996)

Houk et al. suggest that excitatory output from the cerebellar nuclei is fed back into the cerebellum, thus generating a prolonged activity in the cerebellar nuclei which is then molded by inhibitory Purkinje cells. Recent evidence, however, shows that a temporary break in this loop causes a pause in a conditioned eyeblink response, but does not terminate it. [HOUK et al.]
SP0043 The use of zebrafish as an in vivo model for developmental and pathophysiological mineralization
Authors: S. Schulte-Merker
Journal: Annals of the Rheumatic Diseases (2013)

The preparation and application of mucopeptide (MP)-coated latex particles for determining antibody to streptococcal group A MP is described. Anti-MP hyperimmune sera, normal animal and human sera, and commercial antisera to various antigens were tested. MP-latex agglutination proved to be both specific and highly sensitive, permitting the detection of low antibody levels in 20 to 40% of normal sera; these antibodies were not demonstrable by means of other serologic techniques. Data confirming the specificity of the reaction are presented. No cross-agglutinations were observed with the exception of commercial anti-C reactive protein (CRP) serum. This latter phenomenon may be due to traces of MP present in the preparations used to produce anti-CRP serum. Latex agglutination should prove useful for establishing the occurrence of anti-MP antibody and for elucidating the role of anti-MP antibody in the various toxic or inflammatory reactions induced by MP in vitro and in vivo.