tbuckley/cabot-search huggingface dataset:
VALUE OF SPECKLE TRACKING FOR THE ASSESSMENT OF RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH CONGENITAL HEART DISEASE ASSOCIATED PULMONARY HYPERTENSION: CORRELATION WITH CONSERVATIVE ECHOCARDIOGRAPHY AND CLINICAL PARAMETERS
Authors: Hatice S. Kemal, Meral Kayikcioglu, Levent H. Can, Sanem Nalbantgil, Ozcan Vuran, Nesrin Mogolkoc, Hakan Kultursay
Journal: Journal of the American College of Cardiology (2016)
PTH-168 Organisation of an Acute upper Gastrointestinal Bleed Service in an average District General Hopsital
Authors: O D Patani, N Duniak, C Tan, S Khalid
Journal: Gut (2013)

<h3>Introduction</h3> Acute Upper Gastrointestinal Bleed (AUGIB) continues to carry appreciable morbidity and mortality. Organisation and deliverance of emergency care incorporating therapeutic endoscopy is pivotal in the management of AUGIB. Recent British Society of Gastroenterology and NICE guidelines have recommended the introduction of a dedicated AUGIB service in institutions managing patients presenting with AUGIB. Since 2011 we set up a dedicated AUBIG service delivered by a team of gastroenterologists, surgeons and endoscopy support staff. The service currently runs 24 hrs a day and seven days a week. <h3>Methods</h3> Through clinical coding, endoscopy and theatre database we identified all cases of AUGIB for the first year of the service. Data was collected retrospectively from patient case notes, endoscopy reporting system and emergency theatre records. <h3>Results</h3> 77 cases of AUGIB were identified with gender distribution of 56% males and 44% females. The median age of presentation was 67 years (range 20–93 years). Most cases of AUGIB (71%) were acute admissions with the rest occurring among in-patients. A major improvement in the service is that all patients had at least one endoscopy during their presentation with most endoscopies (67%) performed within 24 hours or less and a further (26%) carried out 2–7 days. Endoscopies were performed by gastroenterologist (66%), surgeons (20%) and specialist registrar (14%). About a third (27%) had out of hours (OOH) emergency endoscopies and the remaining procedures were carried out in the dedicated in-patient lists. Majority (62%) of the OOH procedures were done at the weekends. A notable shortcoming was poor risk assessment (18%) at presentation although retrospective risk scoring revealed a median Rockall Score of 3 (range 1–5). At presentation only 8% of patients were admitted to the dedicated gastroenterology ward before the first endoscopy while the majority (52%) were managed initially on the acute medical wards and discharged or subsequently admitted to the gastroenterology ward. <h3>Conclusion</h3> The introduction of a dedicated service has improved the management of AUGIB in our hospital serving a population of 325,000 particularly during the OOH. The findings of this retrospective audit showed an AUGIB service collaborating medical gastroenterologists and surgeons is workable and sustainable in the setting of a district general hospital. To further improve the service a dedicated AUGIB clerking proforma incorporating Rockall risk score assessment is being considered. <h3>Disclosure of Interest</h3> None Declared.
Reply to Mavrogenis et al.
Authors: I. Jovanovic, K. Mönkemuller
Journal: Endoscopy (2011)

We thank Mavrogenis et al. [1] for their interest in our article and their clinically relevant comments regarding the utility of capsule endoscopy in overt obscure gastrointestinal bleeding [2]. Small-bowel tumors are the second most common small-bowel lesion causing obscure gastrointestinal bleeding and account for 5 % – 10 % of cases of small-bowel bleeding [3]. Gastrointestinal stromal tumors (GISTs) often form solid subserosal or intramural masses, sometimes ulcerating or eroding vessels but rarely growing into the lumen [2] [3]. Therefore, gastrointestinal bleeding (acute or chronic) is the most common clinical presentation of GISTs while nonspecific symptoms, such as obstruction, invagination, perforation, or anemia occur in approximately 20 % of cases [2] [3]. We fully agree with Mavrogenis et al. that in cases of more proximal location of lesions there is a real possibility of these lesions being missed by capsule endoscopy due to the rapid capsule transit, bile and/or bubble artifacts, relatively poor luminal distension, and predominantly submucosal growth, generally with intact or only minimally damaged mucosa [2] [3]. Given the comparable diagnostic yield of capsule endoscopy and DBE in the evaluation of obscure gastrointestinal bleeding, there are always the questions of whether these two are competing or complementary technologies and how they should be incorporated in everyday clinical practice. Reports indicate that DBE is the most cost-effective approach for the evaluation of obscure gastrointestinal bleeding especially in emergent cases with massive bleeding, where DBE should be selected over capsule endoscopy, to prevent delay in endoscopic therapy [4] [5] [6] [7] [8].
Abstract 2380: Carcinoembryonic antigen (CEA) directly activates endothelial cells, thereby inducing (tumor)-angiogenesis
Authors: Kira H. Bramswig, Marina Poettler, Waclawa Kalinowska, Bernd R. Binder, Christoph C. Zielinski, Gerald W. Prager
Journal: Cancer Research (2010)

Abstract Angiogenesis has become a major target in treatment of a varietly of cancers, whereby the major angiogenic growth factor VEGF is currently in focus for therapeutic interventions. Nevertheless, the use of VEGF-targeting drugs has been shown to be of limited efficacy, which might lie in the fact that tumor angiogenesis is not only induced by VEGF, but also by a variety of other factors. In this study, we report that the human carcinoembryonic antigen (CEA), a GPI-anchored cell surface adhesion molecule, which is shedded by 70% of human cancers, directly binds to endothelial cells, thereby inducing angiogenic endothelial cell behavior in vitro and in vivo: Overexpressing CEA in endogenous negative renal cell cancer (RCC) cell line or in the sarcoma cell line MethA led to an enhanced tumor angiogenesis and an increase in tumor growth in vivo, effects which were reverted by downregulation of the CEA receptor in endothelial cells via a lentiviral shRNA construct. Furthermore, targeting CEA by CEA mimotope immunized BALB/c mice, led to a breakdown In tumor vascularization, which was reflected by retarded tumor growth. We found that CEA, by binding to its receptor, led to an increase in integrin activation state, leading to enhanced endothelial cell adhesion, followed by amplified adhesion-induced signal transduction, which involved c-src-activation, focal adhesion kinase (FAK) and ERK phosphorylation, as well as PI3kinase/Akt activation. As a consequence, pro-angiogenic endothelial cell behavior, such as migration and invasion or proliferation were induced. Whenever integrin beta-3 were blocked, CEA was effect less in endothelial cells. These results show that the tumor marker CEA might bear hitherto undescribed biological significance in promoting tumor-angiogenesis. Thus, CEA-mediated signaling may offer a potential novel therapeutic target for the treatment of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2380.
P89 Novel mechanisms of immunomodulation by vitamin D and α-1-antitrypsin
Authors: LV Rice, S Dimeloe, J Raynes, A Gupta, O Pfeffe, D Richards, Z Urry, S Farooque, P Ozegbe, E Hornsby, M Nyon, I Haq, J Irving, J McDonnell, S Saglani, A Bush, B Gooptu, C Kemper, C Hawrylowicz
Journal: Thorax (2013)

<h3></h3> Vitamin D deficiency/insufficiency has been associated with poor respiratory health and a predisposition to respiratory disease. Local activation of vitamin D in the airways is important for antimicrobial defenses and suppression of inflammatory responses via the generation of a tolerogenic immune environment. One of the most highly unregulated proteins by vitamin D in CD4+ T-cells is the serine protease inhibitor α-1-antitrypsin. In addition to controlling the pro-inflammatory effects of neutrophil elastase, α-1-antitrypsin also acts via other pathways as an immunomodulator. We have identified a novel axis of immune modulation by vitamin D; where α-1-antitrypsin is able to induce IL-10 production in PBMCs via an interaction with the complement component C3a. Our <i>in vitro</i> findings are supported by <i>in vivo</i> correlations of serum vitamin D, α-1-antitrypsin, C3a and IL-10 in the airways of both asthmatics and healthy controls from a paediatric cohort. We propose that vitamin D is an upstream regulator of the α-1-antitrypsin/C3a/IL-10 axis, providing attractive therapeutic options to promote tolerance in a range of inflammatory diseases.
Abstract P4-05-02: Role of the Atr Protein Kinase and Curcumin in Tumor-Stromal Interactions in Breast Cancer
Authors: A Aboussekhra, MM Al-Ansari, S-F Hendrayani, T. Al-Tweigeri
Journal: Cancer Research (2010)

Abstract Carcinoma-associated fibroblasts (CAFs) play important roles in the genesis and thrive of various types of epithelial cancers, including breast carcinomas. Indeed, various genetic and epigenetic variations have been identified in stromal fibroblasts, and we have recently shown that CAFs as well as their corresponding counterparts (TCFs) display neoplastic-specific changes (Hawsawi et al., 2008). We have also shown that the levels of the tumor suppressor proteins p53 and p21 are down-regulated in CAFs as compared to TCFs. During the cellular response to DNA damage these genes are under the control of important proteins such as Atr, a protein kinase essential for the maintenance of genomic integrity. To further elucidate the molecular changes that occur in breast cancer-associated fibroblasts we assessed the expression of Atr and have shown that the level of the Atr protein kinase is lower in 7 out of 10 (70%) CAFs as compared to their corresponding TCFs. Using specific ATR-siRNA we have shown that ATR negatively controls the expression of various proteins involved in the stromal-epithelial interactions. These include the stromal cell-derived factor 1 (SDF1), the vascular endothelial growth factor (VEGF) and the matrix metalloproteinase-2 (MMP2). In addition, the ELISA assay was used to show that the level of these proteins was higher in the conditioned media from stromal fibroblasts expressing specific ATR-siRNA as compared to control cells. Importantly, serum-free conditioned media from ATR-defective cells stimulated the proliferation and invasion/migration of cultured human breast cancer cells in an SDF1-dependent manner. These results clearly show the role of the breast stromal fibroblast Atr protein in suppressing tumoregenesis in the breast. Moreover, we have shown that curcumin can normalize the expression/secretion of these factors and therefore reduces the invasion/migration of breast cancer cells in vitro. This indicates that curcumin has potential use as stromal fibroblastnormalizing factor that can be utilized for the inhibition of both cancer initiation and recurrence. Hawsawi, N. M., Ghebeh, H., Hendrayani, S. F., Tulbah, A., Al-Eid, M., Al-Tweigeri, T., Ajarim, D., Alaiya, A., Dermime, S., and Aboussekhra, A. (2008). Cancer Res 68, 2717-2725. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-05-02.
Abstract 3646: The role of myeloid-derived suppressor cells in tumor development
Authors: Myrna L. Ortiz, Pingyan Cheng, Noreen Luetteke, Je-In Youn, Dmitry I. Gabrilovich
Journal: Cancer Research (2011)

Abstract Myeloid-derived suppressor cells (MDSC) play an important role in regulation of immune response in cancer. They also have been implicated into promotion of tumor metastases and angiogenesis. We asked what role if any these myeloid cells can play in tumor formation associated in inflammation. To address this question we used previously described S100A9 deficient and S100A9 transgenic mice. S100A9, also known as calgranulin B or myeloid related protein 14 (MRP14), is a member of the S100 family of Ca2+ binding proteins. Previous studies have established that up-regulation of this protein in hematopoietic progenitor cells results in inhibition of dendritic cell maturation and accumulation of MDSC. We tested the role of MDSC in skin tumor formation using TgAC transgenic mice. These mice have activated k-ras mutation in keratinocytes. Upon topical treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) they develop skin papillomas. We generated double transgenic mice and demonstrated that in mice overexpressing S100A9 the frequency and number of papillomas increased dramatically comparing with wild-type TgAC mice. The formation of papillomas was also significantly accelerated. To confirm the critical role of myeloid cells in the observed effect we used bone marrow transfer from wild-type or S100A9 Tg mice into lethally irradiated TgAC mice. Transfer of S100A9 Tg bone marrow cells resulted in significantly more rapid and more extensive formation of papillomas in TPA treated mice than transfer of control bone marrow. To assess effect of TPA treatment on cell infiltrate into skin wild-type or S100A9Tg mice were treated with TPA for 3 weeks. Skin from S100A9Tg mice had significantly higher number of Gr-1+ myeloid cells and CD4+ T cells than skin from wild-type mice. No differences in F4/80 macrophages and CD11c+ dendritic cells were seen. To further evaluate the possible role of MDSC in tumor formation we treat control and S100A9 knockout (KO) mice with combination of carcinogen DMBA and TPA using accelerated skin carcinogenesis protocol. The absence of S100A9 substantially delayed the onset of papilloma and decreased the number of lesions as compared with wild-type mice. These results suggest that MDSC may play an important role in inflammation associated tumoregenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3646. doi:10.1158/1538-7445.AM2011-3646
Increased Sensitivity to Complement of Erythroid and Myeloid Progenitors in Paroxysmal Nocturnal Hemoglobinuria
Authors: Emmanuel N. Dessypris, Douglas A. Clark, L. Clifford McKee, Sanford B. Krantz
Journal: New England Journal of Medicine (1983)

Paroxysmal nocturnal hemoglobinuria is an acquired hemolytic anemia characterized by a membrane defect leading to increased sensitivity of erythrocytes, granulocytes, platelets, and bone-marrow erythroid and myeloid cells to complement-mediated lysis. To determine whether the phenotype of paroxysmal nocturnal hemoglobinuria is also expressed on erythroid and myeloid progenitors, marrow cells from five patients with the disease were exposed to a sucrose hemolytic system and then assayed for colony-forming units—erythroid (CFU—E), burst-forming units—erythroid (BFU—E), and colony-forming units—granulocyte/macrophage (CFU—GM). A 50 per cent or greater decrease in the numbers of erythroid and myeloid colonies was noted when marrow cells from the patients with paroxysmal nocturnal hemoglobinuria were exposed to a sucrose solution of low ionic strength in the presence of complement but not in its absence. Such a decrease was not noted in similarly treated normal marrow cells or in marrow cells from a patient with the disease in remission. These results suggest that in paroxysmal nocturnal hemoglobinuria, CFU—E, BFU—E, and CFU—GM express a membrane abnormality similar to that on erythrocytes, and that the disease is the result of a change occurring at the level of the pluripotent hematopoietic stem cell. (N Engl J Med 1983; 309: 690–3.)
Abstract 422: Early growth response 1 is required for radiation-induced apoptosis in normal tissues.
Authors: Yi D. Zhao, Keith M. Jacobs, Rowan M. Karvas, Dennis E. Hallahan, Dinesh Thotala
Journal: Cancer Research (2013)

Abstract Although radiation therapy is a mainstay of cancer treatments, it can have deleterious effects on normal tissues, leading to poor quality of life for cancer survivors. Radiation can cause depletion of stem cells in normal tissues that can result in late sequelae, including poor learning, cognitive disorders, intestinal malabsorption, infertility, and skin injuries. Our laboratory has shown that low doses of radiation can induce apoptosis selectively in undifferentiated normal stem cells compared to adjacent differentiated cells in multiple niches including the brain and intestine. To elucidate the molecular basis underlying stem cell sensitivity to radiation, we performed discovery research to detect genomic differences between stem cells and differentiated cells. Among the candidates, the Early growth response 1 (Egr1) gene was expressed at high levels in stem cells, but not in isogenic differentiated cells. Egr1 is a zinc-finger transcription factor that is rapidly induced in response to radiation and activates the transcription of pro-apoptotic genes. Since cancer survivors can suffer from cognitive difficulties and intestinal malabsorption, we investigated the role of Egr1 in neuronal and intestinal cell death following irradiation. Knockdown of Egr1 using shRNA increased clonogenic survival in irradiated HT-22 hippocampal neuronal cells and IEC-6 intestinal epithelial cells. This increased radioprotection was largely due to reduced apoptosis in Egr1 knockdown cells. Additionally, suppression of Egr1 promoter binding by mithramycin A and chromomycin A3 also conferred radioprotection to HT-22 and IEC-6 cells. Mouse models further supported Egr1’s role in radiation-induced apoptosis. Egr1 null mice had significantly fewer apoptotic cells in the hippocampus and small intestinal crypts following irradiation, as compared to their wild-type littermates. Finally, we examined mechanisms by which Egr1 regulates radiation-induced apoptosis. Irradiation of HT-22 and IEC-6 cells led to a G2/M cell cycle arrest, which was abrogated by the knockdown of Egr1. Also, knockdown of Egr1 by shRNA and inhibition of Egr1 promoter binding both attenuated radiation induction of the pro-apoptotic factors p53, Bim, and Bax, and upregulated the anti-apoptotic protein Bcl-2. Thus, this study establishes a crucial role for Egr1 in the radiation-induced apoptosis of hippocampal and intestinal tissues. Egr1 could be a potential molecular target to minimize the normal tissue complications associated with radiation therapy. Citation Format: Yi D. Zhao, Keith M. Jacobs, Rowan M. Karvas, Dennis E. Hallahan, Dinesh Thotala. Early growth response 1 is required for radiation-induced apoptosis in normal tissues. [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 422. doi:10.1158/1538-7445.AM2013-422
Assessing Patients' Capacities to Consent to Treatment
Authors: Paul S. Appelbaum, Thomas Grisso
Journal: New England Journal of Medicine (1988)

Abstract The right of patients to accept or refuse recommended treatment requires careful reassessment when their decision-making capacities are called into question. Patients must be informed appropriately about treatment decisions and be given an opportunity to demonstrate their highest level of mental functioning. The legal standards for competence include the four related skills of communicating a choice, understanding relevant information, appreciating the current situation and its consequences, and manipulating information rationally. Since competence is a legal concept and can be formally determined only in court, the clinical examiner's proper role is to gather relevant information and decide whether an adjudication of incompetence is required. Treatment for impairment of mental functioning can sometimes restore patients' capacities, making it unnecessary to deprive them of their decision-making powers. (N Engl J Med 1988; 319:1635–8.)
AB0501 Systolic blood pressure, not nailfold capillary microscopic finding, is the most important factor of arterial stiffness in systemic sclerosis patients
Authors: K.-H. Jung, M. J. Lim, S. R. Kwon, K. Joo, D. Kim, W. Park
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To find the determinants of pulse wave velocity (PWV) and evaluate the association between degree of capillary microscopic changes and PWV in systemic sclerosis (SSc) patients. <h3>Methods</h3> Forty-five systemic sclerosis patients were enrolled. Traditional cardiovascular risk factors, SSc activity/severity markers, hemodynamic factors and microscopic capillaroscopic findings were obtained. Aortic PWV was measured using sequential recordings of the arterial pressure wave at the carotid and femoral arteries. <h3>Results</h3> Most of SSc patients showed low traditional cardiovascular risk factors. Simple and multiple regression analysis showed that radial systolic blood pressure is only a risk factor for increased PWV value in SSc patients. The radial and aortic systolic blood pressure, PWV levels significantly increased with progression of nailfold capillary microscopy changes (p-value = 0.019, 0.020, 0.018, respectively). However, after analysis of covariance using radial and aortic systolic blood pressure as the covariate, it was statistically not significant in PWV levels between early and advanced (active and late) capillary groups (adjusted p-value = 0.526, Table 1). <h3>Image/graph</h3> <h3>Conclusions</h3> Radial systolic blood pressure, not the microscopic capillary changes, is the most important factor of arterial stiffness in systemic sclerosis patients. <h3>Disclosure of Interest</h3> None Declared
AB0804 Effect of capillaroscopic microvascular changes on the pulse oximeter measurements in systemic sclerosis patients
Authors: A. Akdogan, L. Kilic, I. Dogan, Ö. Karadag, S.A. Bilgen, S. Kiraz, I. Ertenli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disorder characterized by microangiopathy, autoimmunity and fibrosis. Capillaroscopy is a simple method for direct observation of microvasculature. The pulse oximeter is a noninvasive instrument used to estimate a patient's arterial blood oxygen saturation. <h3>Objectives</h3> The aim of this study is to investigate the effect of microvascular changes on the pulse oximeter mesurments in SSc patients. <h3>Methods</h3> The nailfolds from 2nd to 5th fingers in both hands were examined in all subjects by using Videocapnet DS Medica –Milano. Patients were categorized according to their capillaroscopy findings in 3 groups as having early, active or late patterns. Oxygen saturation (SO<sub>2</sub>) measurements were performed from 2nd to 5th fingers in both hands with a finger probe. <h3>Results</h3> We screened 56 SSc patients Three SSc patients were excluded. One due to inadequate images for determining the capillaroscopic pattern, 2 due to severe hand deformities that disabled capillaroscopic examination. 53 SSc (F/M:48/5) patients were enrolled into the study. The mean age of the SSc patients was 48,7±11,9 years and 50,9% (27 patients) of the patients had limited SSc. According to capillaroscopy findings 18 patients were classified as having early pattern (34,0%), 19 active pattern (35,8%), 15 late pattern (%28,3). Only 1(1,9%) patient had normal capillaroscopy findings. There were no difference between groups of SSc patients defined as capilleroscopy findings in regard of mean maximal oxygen saturations (SO<sub>2</sub>) or mean minimal SO<sub>2</sub> measured from fingers (p&gt;0,05 for all). <h3>Conclusions</h3> Vasculopathy classes defined by capillaroscopic examination do not affect the S0<sub>2</sub> measured by pulse oximeter in SSc patients. <h3>Disclosure of Interest</h3> None Declared