tbuckley/cabot-search huggingface dataset:
The Influence of Oral Potassium Chloride on Blood Pressure in Hypertensive Men on a Low-Sodium Diet
Authors: Richard H. Grimm, James D. Neaton, Patricia J. Elmer, Kenneth H. Svendsen, Julie Levin, Marvin Segal, Leslie Holland, Lorry J. Witte, Donna R. Clearman, Phillip Kofron, Randall K. LaBounty, Richard Crow, Ronald J. Prineas
Journal: New England Journal of Medicine (1990)

Clinical and epidemiologic studies suggest that the intake of potassium chloride lowers blood pressure. To investigate whether supplemental potassium chloride (96 mmol of microcrystalline potassium chloride a day) reduced the need for antihypertensive medication in hypertensive men on a restricted-sodium diet, we conducted a randomized, placebo-controlled, double-blind clinical trial.
Abstract SY28-01: Is mitosis the target of “anti-mitotic” cancer drugs.
Authors: Timothy J. Mitchison
Journal: Cancer Research (2013)

Abstract Cytotoxic drugs, which mostly target DNA or microtubules, can be curative in some cancers, but how they kill tumor cells selectively compared to normal cells has long been mysterious. The textbook view holds that cytotoxic drugs gain efficacy and selectivity by targeting different phases of the cell cycle, mitosis in the case of anti-microtubule drugs such as paclitaxel. However, the proliferation rate in tumors is slow compared to bone marrow and gut, and drugs that target cells only during cell division have shown little tumor efficacy. It is thus unclear whether mitosis is really a druggable process for cancer treatment. We have investigated the cytotoxic actions of anti-mitotic drugs in cell culture and using intravital imaging in a xenograft tumor model. Comparing the same cell line growing in culture and xenografts, we find that paclitaxel kills via mitotic arrest in culture, but by a non-mitotic mechanism in tumors. Candidate cell-killing mechanisms and their implications for improving chemotherapy will be discussed. Citation Format: Timothy J. Mitchison. Is mitosis the target of “anti-mitotic” cancer drugs. [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 SY28-01. doi:10.1158/1538-7445.AM2013-SY28-01
Abstract P3-12-11: Combining Genotype at Low Penetrance Breast Cancer Loci with Family History Risk Leads to Significant Risk Reclassification
Authors: AJ Martin, S White, A Onen, J Gale, J Dunlop, L Baker, AM Thompson, PDP Pharoah, JN. Berg
Journal: Cancer Research (2010)

Abstract Background: A significant proportion of women are at increased genetic risk of breast cancer. Mutations in high penetrance genes such as BRCA1 and BRCA2 are only responsible in the minority of cases, with low penetrance polymorphisms in other genes expected to account for the majority of the remaining genetic risk. An increasing number of such low penetrance polymorphisms are being identified, but each polymorphism only contributes a small amount to overall risk. Currently, in clinical practice, women who are at increased risk of breast cancer are identified by their family history, and the role of genetic testing for multifactorial risk remains uncertain. We have taken the population frequency and genotype relative risk information for the 18 most established low penetrance breast cancer risk loci and explored the effect of combining information from these loci, with risk derived from family history. Results: Genotyping at these 18 loci could provide significant risk information for an individual. The top 1% of women in the genotype risk distribution would have a risk of breast cancer of 2.11 times the general population. At this level of risk, they would qualify for breast cancer screening from age 40 according to evidence based guidelines issued by the UK National Institute of Clinical Excellence (NICE). In addition, the top 5% of the population are at 1.67 times risk of breast cancer and would have the same risk at age 40 as a 50 year old at population risk who would qualify for breast screening according to UK and US National Screening Guidelines. To investigate whether low penetrance genotype has greater potential if combined with other risk factors, we used a simple multiplicative model to combine family history risk of cancer derived using BOADICEA with genotype information. Our data suggest that genotype would result in a significant reclassification of individual risk. For example, 10% of women who only had a sister affected with breast cancer at 55 would qualify for additional screening under NICE criteria if genotype were taken into account. Extending this approach with 160 complex family histories from the Tayside family history breast clinic, we have shown that genotyping could result in reclassification and change of management for 19.1% of women being assessed in this clinic, with 12.4% of women moving into a higher risk category, and 6.7% of women moving into a lower category. Discussion: These data suggest that genotyping for low penetrance breast cancer risk loci is clinically relevant, and that it will be more powerful if it can be combined with other established risk factors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-11.
OBTENCIÓN DE MUESTRAS HISTOLÓGICAS MEDIANTE ULTRASONOGRAFÍA ENDOSCÓPICA. EXPERIENCIA EN NUESTRO CENTRO
Authors: C González Asanza, B Merino Rodríguez, O Nogales Rincón, L Pérez Carazo, J Miranda, A Ochoa, A Fernández, E Álvarez, P Menchén Fernández-Pacheco
Journal: Endoscopy (2011)

Introducción: La obtención de muestras para histología, a través de punción guiada por ecoendoscopia, presenta ventajas teóricas sobre la citología. Este hecho es más relevante en aquellos centros que no disponen de citólogo en sala
A10.2 Anti-AT1R and Anti-Etar Autoantibodies in Pathogenesis of Systemis Sclerosis
Authors: Angela Kill, Mike O Becker, Jeannine Guenther, Harald Heidecke, Duska Dragun, Gabriela Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> SSc is a prototypic multiorgan disease characterised by vascular damage, autoimmunity and fibrosis with still unkown aetiology. Recently identified functional autoantibodies simultaneously targeting the angiotensin-II type-1 receptor (AT1R-Abs) and the endothelin-1 receptor type A (ETAR-Abs) were linked to vascular and fibrotic complications in SSc. Presence of both autoantibodies moreover predicted mortality due to cardiopulmonary complications implicating their contribution in SSc pathogenesis. Here, autoantibody mediated effects on endothelial cell activation and their blockade by receptor inhibitors were studied. <h3>Materials and Methods</h3> Human microdermal endothelial cells-1 (HMEC-1) and human dermal fibroblasts were treated with IgG from SSc patients containing anti-AT1R and anti-ETAR Abs (SSc-IgG) or with IgG from healthy donors (NC-IgG) as negative control. In parallel, SSc-IgG treated cells were incubated with AT1R-and ETAR- antagonists alone and in combination. Activation of endothelial cells was assessed by qRT-PCR and sandwich ELISA and of fibroblasts with immunocytochemistry. <h3>Results</h3> Human endothelial cells showed increased expression and production of the pro-inflammatory chemokine interleukin-8 (IL-8) upon treatment with SSc-IgG positive for anti-AT1R and anti-ETAR Abs compared to control treatment with NC-IgG as analysed on mRNA and on protein levels. Furthermore, endothelial cells showed increased expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with SSc-IgG versus NC-IgG treatment on mRNA levels. Expression of IL-8 and VCAM-1 was significantly decreased by receptor inhibition. Human dermal fibroblasts showed increased collagen 1 production upon treatment with SSc-IgG versus NC-IgG that was also reduced by receptor inhibition. <h3>Conclusions</h3> Our data sugests a direct involvement of anti-AT1R and anti-ETAR Abs in endothelial cell and fibroblasts activation that is mediated by AT1R and ETAR activation. Increased expression of IL-8 and of VCAM-1 and ICAM-1 indicate a direct endothelial cell activation and inflammation. Increased collagen 1 production indicates fibroblast activation and pro-fibrotic events. Therefore, anti-AT1R and anti-ETAR Abs induce pro-inflammatory and pro-fibrotic events and could be directly involved in the pathogenesis of SSc. In vivo experiments are underway to analyse anti-AT1R and anti-ETAR Abs mediated pathogenic events in SSc.
Abstract P2-10-14: Triple Negative Breast Cancer: prognosis of triple-negative breast cancers and non-triple-negative breast cancers in a large registry of certified breast units
Authors: P Kern, M Rezai
Journal: Cancer Research (2012)

Abstract Background: Prognosis of Triple-Negative Breast Cancer (TNBC) and non-TNBC has been evaluated predominantly in smaller subset of patients, and pooled analyses include various subsets of institutional standards. The West German Breast Center includes more than 200 certified breast units covering approx. 65 % of all breast cancer cases in the country. Material and Methods: We included all primary breast cancer cases of the last 3 years whenever patients received any kind of neoadjuvant or adjuvant chemotherapy in all certified breast units affiliated to the West German Breast Center. Data was submitted in a computer-based registry, where standardized data is prospectively collected. Data monitoring and benchmarking is held 6-monthly which guarantees a high standard of performance. Results: 34 675 non-TNBC patients achieved a DFS of 92,4 % at 2 years and 81,2 % at 3 years whereas out of 3728 TNBC-patients only 79 % were disease-free at 2 years and 57,4 % at 3 years. With regards to overall survival 97,3 % of non-TNBC patients were alive at 2 years and 92,2 % at 3 years, whereas 89,3 % TNBC-patients were alive at 2 years and 82,9 % at 3 years. Conclusion: In this large registry of certified breast units from the West German Breast Center we could underline the significant differences of prognosis as to DFS and OS between the non-TNBC and TNBC-subgroup of patients, displaying survival rates with modern 3rd generation chemotherapy, surgical treatment and radiotherapy in a controlled setting with prospectively collected data. To is, to our best knowledge, one of the largest data sets ever exploring the differences in prognosis between TNBC and non-TNBC-patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-14.
Toxic Effects of Atropine and Homatropine Eyedrops in Children
Authors: Dick Hoefnagel
Journal: New England Journal of Medicine (1961)

THE use of cycloplegic agents in children at times leads to mild side reactions. Redness of the eyes, edema of the eyelids or a brief, moderate elevation in temperature is encountered. Less common, but all the more dramatic and striking in their clinical symptomatology, are the reactions that primarily involve the central nervous system.It is the purpose of this paper to report the clinical histories of 5 children manifesting such reactions after the use of eyedrops containing atropine sulfate or homatropine hydrobromide and to discuss reports of similar cases in the literature.Case ReportsCase 1. A 5-year-old Negro . . .
PTU-164 Cost Effectiveness of an ER Dominant Approach in the Management of High Grade Intraepithelial Neoplasia and Mucosal Cancer in Barrett’S Oesophagus
Authors: P J Basford, G Longcroft-Wheaton, R Mead, P Bhandari
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic resection (ER) is an established effective treatment for high grade intraepithelial neoplasia (HGIN) and intramucosal cancer (IMC) arising in Barrett’s oesophagus. ER can lead to recurrence so it is suggested that all patients should undergo radiofrequency ablation (RFA) after ER as a complimentary treatment strategy. However no comparative study to support this concept has been performed. We aimed to compare the cost-effectiveness of an EMR-dominant approach vs an EMR-RFA approach for the treatment of HGIN and IMC in Barrett’s oesophagus. <h3>Methods</h3> All ER procedures between 2005 and 2012 were recorded in a prospective database which was analysed. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Costs were calculated using NHS HRG codes plus equipment costs for ER and RFA. <h3>Results</h3> 92 patients were treated for dysplastic Barrett’s oesophagus or early Barrett’s cancer by ER. The mean age at first procedure was 69 years and 87% of the patients were male. 21 of 92 patients had advanced histological features on the initial ER specimen and were referred for surgical or oncological treatment. Of the remaining 71 cases, 63 have follow-up data with a mean duration of 4.3 years. 59 of 63 cases (94%) had successful eradication of HGIN/IMC by ER. The remaining 4 patients were referred for surgery for advanced disease (3) or extensive bulky disease not amenable to ER (1). ER was successful in a mean of 1.46 procedures per patient (range 1–3). Complication rate was 5.2% (4 bleeds, 1 microperforation, 2 strictures). Additional RFA was used in 11 cases. 12 (20%) of patients developed recurrence of HGIN/IMC during follow-up requiring further endoscopic therapy. 2 (3.4%) patients developed more advanced Barrett’s neoplasia during follow-up. The calculated cost per patient of an ER-dominant approach is £4125 compared to £8868 per patient for an RFA dominant approach. <h3>Conclusion</h3> ER acted as an accurate and safe staging procedure in up to 23% of cases found to have advanced histology. ER is an effective and safe treatment for HGIN/IMC within Barrett’s oesophagus without the need for routine RFA and can be performed successfully in a UK centre. However the recurrence of HGIN/IMC is not uncommon and therefore close follow-up is required to identify and treat it at an early stage. An ER-dominant approach may offer significant cost-savings compared to an RFA-dominant approach without compromising overall outcomes. <h3>Disclosure of Interest</h3> None Declared
Abstract 5656: Preclinical evaluation of cytotoxic effect of photosensitive fluorescent protein in human cancer cells
Authors: Hiroshi Tazawa, Tsuyoshi Sasaki, Yuuri Hashimoto, Satoru Kikuchi, Hiroyuki Kishimoto, Hiroyuki Mizuguchi, Toshiyoshi Fujiwara
Journal: Cancer Research (2012)

Abstract Photodynamic therapy (PDT) is an anticancer therapy to induce tumor-specific cytotoxicity by accumulation of photosensitizers (PSs) and following non-toxic light irradiation to tumor tissues. Non-toxic light irradiation induces the PS-mediated generation of reactive oxygen species (ROS) and subsequent cytotoxicity in tumor cells. For clinical application, some kinds of PSs, such as photofrin and laserphyrin, are intravenously injected before light irradiation in anticancer PDT. However, the lack of sufficient and continuous accumulation of PSs in tumor tissues makes difficult to eradicate tumor cells by PDT. Therefore, the development of novel PSs that accumulate to tumor tissues more efficiently and persistently is required to improve the antitumor effect of PDT. Recently, a bioengineered fluorescent protein KillerRed has been reported to generate ROS upon green light irradiation, suggesting a potential of KillerRed fluorescent protein as a novel PS. In this study, we investigated the antitumor effect of KillerRed fluorescent protein in human cancer cells in combination with PDT. Transient transfection with KillerRed expression vector induced the photosensitive cytotoxicity upon green light irradiation within a few hours in human cancer HeLa and OST cells. To further evaluate the cytotoxic effect of KillerRed fluorescent protein in human cancer cells, we obtained the stable transfectants expressing cytotoxic KillerRed or non-cytotoxic Katushka fluorescent protein from human lung cancer H1299 cells. Green light irradiation induced the cytotoxic effect within one hour in H1299-KillerRed cells, but not in H1299-Katushka or H1299 cells. H1299-KillerRed cells irradiated with green light showed significantly higher levels of ROS, which was confirmed by intracellular fluorescence level of 2′,7′-Dichlorodihydrofluorescein Diacetate, than H1299-Katushka or H1299 cells. Immunocytochemistry further revealed that green light-irradiated H1299-KillerRed cells showed the apoptotic cell death with the cleavage of caspase-3 24 hours after irradiation. These results suggest that KillerRed fluorescent protein is a potent novel PS inducing ROS generation and apoptotic cell death in tumor cells in anticancer PDT. The development of virus-mediated delivery system for tumor-specific induction of KillerRed fluorescent protein is under way. 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 5656. doi:1538-7445.AM2012-5656
Abstract 988: A diet and exercise intervention in women being treated for breast cancer
Authors: Zora Djuric, Jennifer Ellsworth, Mary Rapai, Anne Weldon, Jihye Kim, Ananda Sen
Journal: Cancer Research (2010)

Abstract Increases in body fat have been documented to occur in breast cancer patients during chemotherapy and radiation treatment. This is a matter of concern that can impact on health status in survivorship, especially given the difficulties in achieving weight loss once a gain has occurred. Weight gain and obesity have also been linked with recurrence. In this pilot study we investigated the feasibility of recruiting women early in their breast cancer treatment to a study that sought to prevent body fat gain. The study randomized women to receive written materials only or telephone counseling. The goals of the counseling were to decrease fat intake, increase fruit and vegetable intakes and to include at least 30 minutes of moderate to vigorous exercise daily. The counseling stressed self-monitoring of these behaviors. A total of 40 women were enrolled within 2 weeks of starting chemotherapy. This was 53% of the women who were referred to the study by their oncologists over 8 months. Baseline BMI was a mean of 27 (range 18-43 kg/m2) and 19 women were in the normal BMI range. Only 11 women had a body fat percentage in the recommended range. Retention of subjects for 12 months was 75% overall but it was better in the written arm (17 of 20 women) than in the telephone arm (13 of 20 women). Body fat increased in the written arm from 39.2 to 40.8% but it decreased from 39.0 to 37.3% in the telephone arm. Other objective measures also improved in the telephone arm such as blood pressure and leptin levels. Both total and moderate/vigorous activity increased more in the telephone arm than in the written arm. Improvements in dietary intakes at 12 months were noted in the telephone arm but not in the written arm. This preliminary data indicates that telephone support is helpful for making lifestyle changes that prevent body fat gain during treatment for breast cancer. Subject satisfaction with the study was high. The prevention of body fat gain during treatment for breast cancer is therefore feasible, and this approach could be useful for maximizing health in survivorship. Supported by the University of Michigan Metabolomics and Obesity Center, the Michigan Diabetes Research and Training Center, the Barbara Padnos Breast Cancer Research Fund and the Michigan Institute for Clinical and Health Research. 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 988.
AB0726 How Early we can Diagnose Ankylosing Spondylitis?
Authors: T. Dubinina, S. Erdes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> There is a need for an early diagnosis in all patients with ankylosing spondylitis (AS). How early we can diagnose AS, if disease begins with low back pain (LBP)? <h3>Methods</h3> Were interviewed 74 pts (mean age – 31.6±7,7 yrs) with diagnosis of AS (modified New York criteria) whose disease began with LBP: 51 (68,9%) males and 31 (31,1%) - women. The mean disease duration - 10.9±6,0 yrs (min - 12 months., max. - 25 years). <h3>Results</h3> Making diagnosis of AS were observed for the following 3 stages. 1 stage - from the onset of LBP before the first patient visit to the general practitioner (GP). According to our data, the patients visit to the GP on average 1,5±0,7 yrs from the beginning of LBP (min 6 mth, max - 10 yrs). There were identified the following reasons for the late visit to the GP: mild symptoms at presentation LBP had 68 pts (91,9%), most patients (68,4%) had recidivating character of LBP, in 21 pts (28,4%) simulates radiculopathy. Morning stiffness was present in 37 pts (50,0%), only 20 (27,0%) had night pain. LBP quickly reduce after use NSAIDs and taking regular exercise. Stage 2 - referral of patient with LBP to the rheumatologist. The first consulting by rheumatologist was 5,0±4.2 yrs (min - 1 year, max 20 yrs) after the first visit GP. Before consulting by rheumatologist, all patients had visited one or more physician (orthopedist, neurologist and other) who had given them one or more diagnosis. The total number of visits physicians before rheumatologist consulting - 7,0±5,4 times (min 1, max- 25). There was positive correlation between making diagnosis and first visit to the rheumatologist (r=0.9, p=0.001). Stage 3 - correct diagnosis of AS. Mean delay in diagnosis was 1.8±0.5 yrs from first visit to the rheumatologist, because standard radiography of the sacroiliac joints was normal. <h3>Conclusions</h3> Early diagnosis of AS may be difficult in the first 1,5 yrs due to a variety of reasons including late visit patients to the GP and mild to moderate symptoms at disease onset. Stage 2 can be shortened by educational programs for GP and other specialists. Stage 3 - is necessary to revise the modified New York criteria, because they limit the diagnosis of AS in the early stages. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3173