tbuckley/cabot-search huggingface dataset:
SAT0081 Seropositivity is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis Patients: Results from the Norfolk Arthritis Register
Authors: S. Skeoch, S. Verstappen, J. Chipping, T. Marshall, D. Symmons, I. Bruce
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have a 50% increased risk of cardiovascular disease (CVD) not fully explained by traditional risk factors. Arterial stiffness is an independent predictor of CVD and can be measured non-invasively using mobile, operator independent devices. RA patients have been found to have increased arterial stiffness compared to controls and improvements have been demonstrated, following anti-TNF therapy. <h3>Objectives</h3> The aim of the current study is to investigate the relationship between arterial stiffness and disease characteristics in a cohort of patients with established inflammatory polyarthritis (IP). <h3>Methods</h3> Arterial stiffness was measured in a subset of patients in the Norfolk Arthritis Register (a primary inception cohort of patients with adult onset IP), at 15 year follow up. The stiffness index (SI), an indirect measure of arterial stiffness, was measured using an automated digital photoplethysmography device (Pulse Trace PCA2, Micromedical). Concurrent clinical assessment was performed, including disease activity 28 score (DAS-28 score) and blood was taken for CRP measurement and serological status with seropositivity being defined as being positive for rheumatoid factor and/or anti-citrullinated protein antibody positive (ACPA). The patient completed a health assessment questionnaire (HAQ). Non-parametric tests were used to test correlation of SI with IP disease characteristics and traditional CVD risk factors. <h3>Results</h3> Arterial stiffness was measured in 33 subjects. Median (IQR) age was 61.0(44.9, 71.9) years and 23(69.7%) were female. 28(84.8%) of subjects were seropositive. Median DAS-28 score was 3.23(2.41, 3.34), HAQ score was 1.00(0.25, 1.5) and CRP was 8.71(6.8, 18.8)mg/dl. The proportion of patients with a history of clinical CVD, hypertension and diabetes was 12.1%, 36.4% and 9.1% respectively. The median (IQR) SI was 10.05(8.98, 10.79) m/s. SI was significantly higher in subjects who were seropositive (p=0.02) and there was a trend towards a correlation between SI and CRP (rho=0.36, p=0.08). There was no significant association with traditional CVD risk factors or prior history of clinical cardiovascular events. <h3>Conclusions</h3> In this small exploratory study, seropositive patients had increased arterial stiffness. This finding is in agreement with previously observed increased risk of clinical CVD in these patients. The low number of clinical cardiovascular events in the cohort may explain the lack of association of SI with history of CVD in this study. Digital photoplethysmography could provide an effective, non-invasive tool with which to investigate and monitor cardiovascular risk in RA. <h3>Disclosure of Interest</h3> None Declared
Intradermal Desensitization with Human Insulin (recombinant DNA) in a Patient with Severe Allergic Skin Reaction due to Insulin
Authors: Werner Bachmann, Helmut Hasche, Hellmut Mehnert
Journal: Diabetes Care (1982)

This is a case report of a 70-yr-old female patient with a severe allergic skin reaction (necroses) due to insulin injections. Because of insulin dependency, desensitization to insulin was mandatory. For desensitization, a schedule with intradermal injections of increasing insulin concentrations (from 0.02 to 2 U per injection) at time intervals of 3 h was used. With highly purified pork insulin, the concentration limit of 0.04 U was reached in spite of 75 injections. After changing to human insulin (recombinant DNA), a rapid desensitization could be performed at the same concentration. Desensitization resulted not only to human insulin but also to highly purified pork insulin, as shown by intradermal testing 6 mo later.
PWE-261 Have you heard of the Truelove and Witts criteria? acute severe ulcerative colitis management by FY1 doctors
Authors: V Chhaya, Y Squire, N Siva, A Poullis
Journal: Gut (2012)

<h3>Introduction</h3> Acute severe ulcerative colitis (UC) is a serious illness that requires prompt hospitalisation and is associated with significant morbidity. It requires intensive monitoring, specialist intervention and a multidisciplinary approach throughout the duration of the illness with timely and appropriate medical and surgical interventions to avoid complications. Our aim was to evaluate the Foundation Year 1 (FY1) doctor9s knowledge and understanding of this potentially life threatening emergency. <h3>Methods</h3> We approached FY1 doctors with an example case of acute severe UC and a questionnaire asking several questions regarding the diagnosis and management of acute severe UC 5 months into their training in 2011. <h3>Results</h3> 48 FY1 doctors completed the questionnaire during a medical teaching session. Only 25% had heard of the Truelove and Witts criteria as a tool for assessing the severity of UC. When asked regarding the criteria, 77.08% recognised stool frequency as one, 72.91% heart rate, 62.5% temperature, 41.67% haemoglobin and 35.42% erythrocyte sedimentation rate (ESR) as part of it. 58.33% of those asked diagnosed the example case as an acute severe UC, however only 43.75% stated that they would request daily abdominal x-rays as part of their management plans. 62.5% of those asked knew intravenous corticosteroid therapy was mainstay of the initial treatment. 72.92% answered correctly regarding the use of thromboprophylaxis as standard therapy in the management of the condition and 79.17% said they would regularly check the serum potassium level during the course of the presentation. <h3>Conclusion</h3> This study highlights the lack of knowledge and understanding of the diagnosis and management of acute severe UC by the FY1s. We would recommend a more structured approach to teaching regarding the condition at all levels of training during planned sessions. Protocols for admission and management of acute UC and local acute medicine hospital guidelines may aid education and bridge gaps in knowledge. <h3>Competing interests</h3> None declared.
Plasma Exchange in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Authors: Peter James Dyck, Jasper Daube, Peter O'Brien, Alvaro Pineda, Phillip A. Low, Anthony J. Windebank, Carol Swanson
Journal: New England Journal of Medicine (1986)

Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P<0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder. (N Engl J Med 1986; 314: 461–5.)
Abstract 1852: Identification of the UV-inducible RNA binding protein hnRNP A18 as a new target for melanoma progression
Authors: Qingyuan Yang, France Carrier
Journal: Cancer Research (2012)

Abstract Melanoma is the most dangerous form of skin cancer. If recognized and treated early, it is nearly 100 percent curable. However, invasive melanoma is hard to treat and consequently presents an extremely poor prognosis with a 5-year survival of about 6% and a median survival duration of 7.5 months. We have identified the UV-inducible RNA binding protein hnRNP A18 as a new target for melanoma progression and responses to anticancer drugs treatments. hnRNP A18 basal levels are up-regulated in melanoma cells as compared to normal melanocytes and UV radiation increases hnRNP A18 levels in 5 of the 6 melanoma cell lines we studied. More over, down regulation of hnRNP A18 reduced by more than 80% melanoma tumor growth in mice xenograft and sensitized melanoma cells to Temozolimide (TMZ) and the hypoxic mimetic agent CoCl2. In addition, levels of hnRNP A18 expression in response to UV radiation are proportional to melanoma cells capacity to survive UV-induced cellular damage. We have identified an hnRNP A18 RNA binding signature motif in the 3′ UTR of key regulatory proteins such as HDAC 8, 9, 11, HIF-1α and ATR that can confer resistance to UV induced DNA damage and hypoxic conditions. Therefore by targeting of a single molecule, hnRNP A18, it may be possible to shut down an entire network of protective proteins conferring melanoma cells, and potentially other solid tumors, growth advantage and resistance to conventional therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1852. doi:1538-7445.AM2012-1852
THE EFFECTS OF ENDOSCOPIC SEVERITY AND BIOLOGIC TREATMENT ON LEVELS OF DEPRESSION AND DISABILITY AMONGST IBD PATIENTS:A CASE CONTROL STUDY
Authors: M Khan, P Calpin, O Kelly, J Moloney, E McDermott, H Mulcahy, A Aftab, G Courtney
Journal: Gut (2013)

<h3>Introduction</h3> As with other chronic diseases, patients with IBD are also at risk for depression, anxiety, low self-esteem and social isolation. The physical symptoms in gastrointestinal disease, including diarrhoea, bleeding per rectum and faecal incontinence are much less socially acceptable than other chronic diseases. Together with the potential for surgery, including stoma formation, this results in a high risk for altered body image and psychosocial distress unique to IBD. <h3>Aims/Background</h3> In this study we aimed to compare the effects of disease activity on body image and quality of life in these patients and also to assess whether biological treatment offers superior clinical and psychological outcomes or reduction in disability. <h3>Method</h3> Patients taking biologics attending St. Luke9s IBD service were asked to complete a questionnaire including the Body Image States Scale (BISS), the Stunkard Figure Rating Scales (FRS), the Hospital Anxiety and Depression scale (HADS), the Beck Depression Inventory (BDI), the SF 36 Health Survey, the IBDQ and the sexual satisfaction survey. Clinical markers of disease severity were also examined including recent endoscopic findings, Mayo score and CRP. These were then age and sex matched with IBD patients not taking biologics. Results were statistically analysed p values&lt;0.05 were deemed significant. <h3>Results</h3> 64 IBD patients were included in this study. 32 patients were taking biologics at time of study (60% M) Median age was 41; IQR (31-54). 55% had UC, 33% had Crohn9s, 13% had indeterminate colitis. These were age, sex and disease matched with 32 respondents not taking biologics. Mayo scores, Hb and CRP were not significantly different between groups. Endoscopic severity was increased in the biologic group though not significantly. There was no significant difference in Beck Depression Inventory scores between treatment groups, however those on biologic treatment who were in remission reported significantly lower disability using the Disability Index (Peyronie <i>et al</i>, 2012) compared to their peers in remission not on biologics (p&lt;0.05). Endoscopic severity was found to be independently associated with higher Beck depression Inventory scores (p&lt;0.01). <h3>Conclusion</h3> Depression is common in IBD. Clinical and mucosal remission may not only lead to reduced inflammation but also to reduced levels of depression. Treatment with biologics appears to be associated with lower levels of disability in patients with similar pre-treatment clinical severity scores.
P04.26 * MOLECULAR MECHANISMS OF CIRCULATING MICRORNA BIOMARKERS FOR GLIOBLASTOMA
Authors: C. A. Tumilson, J. E. Alder, R. W. Lea, L. Shaw
Journal: Neuro-Oncology (2014)

The development of biomarker panels for glioblastoma has the potential to greatly improve the outcome of treatment by assisting in earlier detection, determining response to treatment and predicting prognosis to improve therapeutic strategy. MicroRNAs (miRNAs) present in the circulation of glioblastoma patients provide a relatively non-invasive source of markers for this purpose. Gliomas, including glioblastoma, release miRNAs in exosomes and protein complexes which alter expression levels in the serum of patients. The aim of this study was to isolate and identify deregulated miRNAs from the sera of glioblastoma patients which could be used as biomarkers. Further to this, the molecular mechanisms behind the deregulation of these miRNA biomarkers were also determined. Total RNA was isolated from the sera of glioblastoma patients, patients undergoing elective surgery and volunteers, using phenol-chloroform extraction. Relative expression of miRNAs was determined using qRT-PCR and normalized using a synthetic spike in. Data was analysed using GraphPad Prism 5 software using the delta CT method. Statistical significance was determined using a t-test and one way ANOVA, a p-value of <0.05 was considered significant. Three miRNAs were significantly deregulated in the sera of glioblastoma patients compared to control sera. One prognostic marker determined by Kaplan-meier analysis, one male specific marker and one age-specific marker which could be used as a panel for glioblastoma patients. Further work using glioblastoma tissue will elucidate the role of these miRNAs in glioblastoma including the underlying molecular differences between patients exhibiting deregulated miRNA and subsequently improved prognosis.
FRI0268 Dna demethylation characterizes salivary gland epithelial cells from patients with primary sjögren’s syndrome
Authors: D. Cornec, Y. Thabet, C. Le Dantec, I. Ghedira, V. Devauchelle-Pensec, Y. Renaudineau, J.-O. Pers
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by an epithelium injury with dense lymphocytic infiltrates composed of activated T and B cells. Present at the interface of genetic and environmental risk factors, epigenetic modifications are suspected to play a key role in SS. <h3>Objectives</h3> to characterize DNA methylation in SS. <h3>Methods</h3> 5 methyl cytosine (5MeCyt) ELISA tested global DNA methylation within long-term culture salivary gland epithelial cells (SGEC) and peripheral blood T and B cells from eight SS patients. DNA methylation/demethylation partners were tested by real time quantitative PCR (DNMT1, DNMT3a/b, PCNA, UHRF1, MBD2, MBD4, and Gadd45-alpha). Immunofluorescence was conducted on labial salivary gland biopsy. Co-culture experiments were performed using the human salivary gland cell line (HSG) and B cells. <h3>Results</h3> Global DNA methylation was reduced in SGEC from SS patients (5MeCyt: 36.3±3.2% in SS <i>versus</i> 43.1±3.3% in controls, <i>P</i>=0.01), while no differences were observed in T and B cells. SGEC demethylation in SS patients was associated with a 7-fold decrease in DNA methyl transferase (DNMT) 1 and a 1.8-fold increase in Gadd45-alpha expression. The other DNA methylation/demethylation partners tested were not different from controls. Interestingly, SGEC demethylation may be attributed in part to the infiltrating B cells as suspected from the analysis of salivary gland biopsy in SS patients treated with rituximab (anti-CD20). Such hypothesis was confirmed using co-culture experiments with HSG cells and B cells revealing an alteration of the ERK/DNMT1 pathway. Finally, several SGEC genes were overexpressed due to DNA methylation changes including ICAM-1 and human endogenous retrovirus (HERV). <h3>Conclusions</h3> As a consequence, part of the SGEC dysfunction in SS may be linked to epigenetic modifications and this tissue-specific defect may be ascribed in part to infiltrating B cells, thus opening new therapeutic perspectives in SS. <b>Disclosure of Interest</b>: None Declared
Effect of Propranolol on Myocardial-Infarct Size in a Randomized Blinded Multicenter Trial
Authors: Robert Roberts, Charles Croft, Herman K. Gold, Tyler D. Hartwell, Allan S. Jaffe, James E. Muller, Suzanne M. Mullin, Corette Parker, Eugene R. Passamani, W. Kenneth Poole, Daniel S. Raabe, Robert E. Rude, Peter H. Stone, Zoltan G. Turi, Burton E. Sobel, James T. Willerson, Eugene Braunwald
Journal: New England Journal of Medicine (1984)

A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were similar in the two groups. The primary end point evaluated--infarct size as estimated from plasma MB creatine kinase activity--was virtually identical in the two groups, averaging 13.3 and 13.6 gram-equivalents of MB creatine kinase per square meter of body-surface area. Peak plasma levels of the enzyme were also similar in the two groups. No significant difference was observed between the propranolol and placebo groups in the change in left ventricular ejection fraction, extent of area involved in pyrophosphate uptake, R-wave loss on electrocardiograms, or mortality (after three years). These results do not support the use of propranolol administered four or more hours after the onset of symptoms to limit infarct size.
THU0448 Safety competences knowledge and behavioural skills of patients treated by biologics in rheumatology:
Authors: A.-C. Rat, B. Fautrel, E. Flipon, L. Gossec, B.-D. Caritey, L. Margerie, H. Nataf, M. Piperno, B. Pallot Prades, R.M. Poilvert, V. Royant, F. Sadji, C. Sordet, C. Thevenot, C. Beauvais
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Biologics are known to entail specific risks; therefore teaching patients safety competences and what decisions to take in some situations is necessary. The level of knowledge of safety competences are not well known in patients treated by biologics. <h3>Objectives</h3> The objective was to describe the safety competences of a representative sample of patients treated by biologics for inflammatory arthritis in order to find which ones should be better highlighted. <h3>Methods</h3> Data were obtained from a national cross-sectional survey. Rheumatologists were randomly sampled from the national directory. They were invited to include 3 to 5 consecutive patients treated by biologics whatever their inflammatory arthritis diagnosis. All patients completed a 54-item questionnaire addressing safety competences and sociodemographic, types of information received, quality of life and coping style data. The questionnaire to measure knowledge and skills regarding biologics was developed by health professional and patients using 3 steps: elaboration of a comprehensive list of competences, selection via a Delphi technique, elaboration of a questionnaire for the 26 competences selected. The questionnaire includes a series of multiple-choice questions on knowledge and on clinical situations grouped in dimensions*. <h3>Results</h3> Of the 671 patients included, 67% were women, 62% had RA and 38% spondylarthritis, 63% were treated by subcutaneous antiTNF. The mean age was 53±13 years old. Patients received information during a medical consultation (90%), a consultation with a nurse (30%), with a written booklet (59%) and during a therapeutic education program (11%). The median total score (sum of the items)was 39 (range 1-53).Knowledge questions had not higher percentages of correct answers than behavioural skills items. Scores and number (%) of patients with a number of correct answers lower than 50% are described in the table. For pregnancy score, 42% of women and 66% of men answered incorrectly to the 2 items.The Scores are the sums of item <h3>Conclusions</h3> Safety competences of patients under biologics can be improved. There is a need for patient education and counselling to improve security and behavioural skills in biologic-treated patients <h3>References</h3> L Gossec. Ann Rheum Dis 2010;69(Suppl3):476 <h3>Disclosure of Interest</h3> None Declared
Aphthous lesions of the colon as a manifestation of metastasized breast cancer
Authors: A. Hirano, S. Nakamura, K. Fujita, M. Hirahashi, T. Matsumoto
Journal: Endoscopy (2011)

A 55-year-old woman underwent right radical mastectomy in 2000 for an invasive ductal carcinoma of the right breast without lymph node metastasis. Although the patient subsequently received adjuvant chemotherapy, she developed a solitary minute gastric metastasis, which was removed by endoscopic resection [1]. She was treated by chemotherapy for the following 6 months. Thereafter, the clinical follow-up showed no signs of tumor recurrence.