tbuckley/cabot-search huggingface dataset:
Abstract 149: Transgenic Overexpression Of HCN4 Induces Right Ventricular Dilated Cardiomyopathy Through Calpain-mediated Apoptosis
Authors: Pessah Yampolsky, Thomas Fink, Rüdiger Becker, Michael Koenen, Hugo A Katus, Dierk Thomas, Patrick A Schweizer
Journal: Circulation Research (2013)

Introduction: Hyperpolarization-activated cation (HCN) channels encode the pacemaker current If that contributes to generation and regulation of sinus rhythm, with HCN4 representing a key component in the cardiac conduction system. Recent studies have identified an increased ventricular expression of HCN4 in patients with hypertrophic cardiomyopathy and heart failure, however the mechanistic involvement of HCN4 in pathogenesis remains unresolved. Methods: We generated transgenic mice that overexpress human HCN4 under the regulation of a cardiac-specific cTNI promoter (HCN4+ mice) to study the contribution of HCN4 overexpression to structural heart disease. Molecular mechanisms were analyzed by quantitative Real-time PCR, western blot and immunohistochemistry. Results: HCN4+ mice were viable and exhibited high expression of HCN4 in both atria and ventricles, with HCN4 protein abundantly targeted to the plasma membrane. Real-time PCR analysis showed a 71% reduction in transcript levels of the endogenous murine HCN4 gene. Morphological evaluation at different developmental stages revealed right ventricular dilation and progressive decrease in wall thickness after one month of age, lacking overt myocardial hypertrophy, significant fibrosis or signs of myocardial inflammation. On the cellular level, the changes were characterized by apoptotic cell loss induced by strong transient expression of mu-calpain Ca2+-sensor and tissue transglutaminase (243% and 397% of wild type, respectively), which resulted in a robust activation of caspase 3. Of note, markers of pathological hypertrophy, that is atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (beta-MHC) remained unchanged. At the same time transcription of the physiological cell growth markers glycogen synthase kinase 3-beta (GSK3B) and mammalian target of rapamycin (mTOR) was elevated. Conclusion: HCN4 overexpression leads to calpain-mediated apoptosis and is associated with right ventricular dilated cardiomyopathy in a transgenic mouse model.
Demonstration of Positional Posterior Circulation Cerebral Ischemia on Cerebral Blood Flow SPECT
Authors: NORIYUKI SHUKE, KENICHI NAGASAWA, WAKAKO YAMAMOTO, KOUKI USUI, KAZUHIRO SAKO, HIROFUMI NAKAI, TATSUYA TANAKA, TAMIO ABURANO
Journal: Clinical Nuclear Medicine (2001)

SHUKE, NORIYUKI M.D.; NAGASAWA, KENICHI M.D.; YAMAMOTO, WAKAKO M.D.; USUI, KOUKI M.D.; SAKO, KAZUHIRO M.D.; NAKAI, HIROFUMI M.D.; TANAKA, TATSUYA M.D.; ABURANO, TAMIO M.D. Author Information
Relationship between Nonmedical Prescription-Opioid Use and Heroin Use
Authors: Wilson M. Compton, Christopher M. Jones, Grant T. Baldwin
Journal: New England Journal of Medicine (2016)

A large fraction of heroin users now report that they formerly used prescription opioids nonmedically, a finding that has led to restrictions on opioid prescribing. Nevertheless, only a small fraction of prescription-opioid users move on to heroin use.
EFFECTS OF ANTIHYPERTENSIVE THERAPY CLASS ON PROGRESSION OF CAROTID ARTERIAL STIFFNESS OVER TEN YEARS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Adam D. Gepner, Yacob Telda, Matthew Tattersall, Laura Colangelo, Claudia Korcarz, Joel Kaufman, Kiang Liu, Philip Greenland, James Stein
Journal: Journal of the American College of Cardiology (2016)
ANGIOGRAPHIC AND OPTICAL COHERENCE TOMOGRAPHY-DERIVED MORPHOLOGICAL PREDICTORS OF PHYSIOLOGICALLY SEVERE CORONARY STENOSIS DETERMINED BY FRACTIONAL FLOW RESERVE
Authors: Eisuke Usui, Tsunekazu Kakuta, Tetsumin Lee, Tadashi Murai, Yoshihisa Kanaji, Junji Matsuda, Makoto Araki, Takayuki Niida, Sadamitsu Ichijo, Rikuta Hamaya
Journal: Journal of the American College of Cardiology (2016)
Treatment of Congestive Heart Failure in Ambulatory Patients with Salyrgan-Theophylline Administered Orally
Authors: Julius Abramson, Elliott Bresnick, Peter L. Sapienza
Journal: New England Journal of Medicine (1950)

IN ANY outpatient cardiac clinic are to be found considerable numbers of patients who must report to the hospital for injections of mercurial diuretics as often as several times each week. The present study was motivated by a desire to relieve many of these people of this burden.The patients in this study were entirely unselected except that they all gave evidence of severe congestive failure requiring mercurial diuretics for maintenance. Most had been receiving mercurial injections once or twice a week. Others had needed one only every four to six weeks. At the other end of the scale was . . .
Tips for a Physician in Getting the Right Job, Part VI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2013)

This article examines numerous general questions and possible responses that will be of special interest for those doctors interviewing for an administrative position. These queries will be presented under the topic headings of why do you want to change jobs, what are your strong and weak points, what are your credentials to do this job well, and what are your career objectives. However, some of these questions and answers will also be helpful to those physicians seeking a clinical job. Additional types of questions and answers, such as those found in behavioral, situational, and stress interviews, will be discussed in subsequent articles.
Multiple Extrapulmonary Sites of Accumulation of Ga-67 Citrate in Sarcoidosis
Authors: N Fukumitsu, M Oshima, M Uchiyama, Y Mori
Journal: Clinical Nuclear Medicine (1999)

A 27-year-old man with widespread lymphadenopathy had multiple sites of accumulation on Ga-67 imaging. The diagnosis of sarcoidosis was confirmed by biopsy. In addition to Ga-67 uptake in intrathoracic lymphadenopathy, Ga-67 was seen at multiple extrapulmonary sites of sarcoidosis.
ANALISIS DE POSIBLES VARIABLES QUE INFLUYAN EN EL DIAGNOSTICO ENDOSCOPICO DE LOS ADENOMAS COLORRECTALES
Authors: F Borda, FJ Jiménez, A Borda, M Basterra, JJ Vila, JM Zozaya
Journal: Endoscopy (2011)

Introduccion: Actualmente se discuten los posibles factores que influyen en la tasa de adenomas diagnosticados endoscópicamente.
Maintenance with the TLR-9 agonist MGN1703 versus placebo in patients with advanced colorectal carcincoma (mCRC): A randomized phase II trial (IMPACT).
Authors: Jorge Riera-Knorrenschild, Hans-Joachim Schmoll, Dirk Arnold, Hendrik Kroening, Frank Mayer, Dieter Nitsche, Reinhard Ziebermayr, Werner Scheithauer, Johannes Andel, Christian Meisel, Manuel Schmidt, Burghardt Wittig
Journal: Journal of Clinical Oncology (2013)

3643 Background: Standard induction chemotherapy for mCRC is often discontinued in patients responding to the treatment. MGN1703, a synthetic DNA-based immunomodulator, acts as TLR-9 agonist. This trial has been conducted to assess clinical efficacy, safety, and immunogenicity of MGN1703 as maintenance therapy vs placebo. Methods: The IMPACT trial is an international, multicenter, randomized (2:1) double-blind placebo-controlled phase 2 trial in mCRC patients with disease control (CR, PR, SD) after 4.5 to 6 months of 1st-line induction chemotherapy with FOLFOX/XELOX or FOLFIRI +/- bevacizumab. Results: 59 patients have been randomized (43 MGN1703, 16 placebo). Median PFS from start of maintenance was not different with 2.8 vs 2.7 months, however the HR was 0.56 (CI 95%: 0.29-1.08; p=0.069) in favor of MGN1703, due to a small favorable subgroup with long-term PFS (20% vs 0% at 9 months; p=0.006). Total PFS from beginning of induction chemotherapy including maintenance was significantly improved: HR 0.49 (CI 95%: 0.25-0.94), p=0.029. After a median follow-up of 13 months 66% of patients are still alive (67% vs 62%), therefore survival data are still preliminary (HR 0.79; CI 95%: 0.3-2.1) and will be mature at the meeting. Activation of cellular immune function as indicated by significant increase of CD14 + CD169 + monocytes was observed in all but one of the MGN1703 treated patients, while absent in all placebo patients. Treatment was well tolerated: 46.5% vs 31.3% of patients (MGN1703 vs placebo) had any drug-related adverse events (AE) and 20.9% vs 18.8% had AE with grade 3 or 4 (including hypertension, ileus, sepsis, sensory polyneuropathy, nausea/vomiting for MGN1703 and pain, popular exanthema for placebo). Conclusions: MGN1703 maintenance seems to prolong PFS in a subgroup of patients with disease control after induction chemotherapy vs placebo, and is associated with relative mild toxicity. This in an early signal in a selected and very limited patient population which supports further investigation. Predictive biomarkers are under evaluation to identify a potential subgroup which might have benefit from this TLR-9 MGN1703 maintenance. Clinical trial information: NCT01208194.
Abstract C70: Rapid viscosity-based diagnostic for hyperviscosity in leukemia patients
Authors: Lena van Nimwegen, Cedric Hurth, Frederic Zenhausern
Journal: Cancer Research (2009)

Abstract The rapid viscosity-based diagnostic test is designed to determine a method by which whole blood viscosity can be clinically tested, in a manner that is both time and cost effective. Leukemia, as well as other blood cell diseases such as Waldenstrom's macroglobulinemia, is associated with hyperviscosity, due to an increase in particular components of blood. Our goal is to use high speed video imaging to characterize the rheological properties of a whole blood sample in order to qualitatively determine the viscosity of the sample. Previous reports used rapid video imaging to describe the mechanics of fluid flow upon impact by a solid sphere (C. Duez et al, Nature Physics 2007, 3, 180–183). The primary method of characterization relies upon the determination of a threshold impact velocity at which the resulting splash profile transitions from a blob to a jet. We performed preliminary tests using a series of glycerol dilutions to mimic potential differences in blood viscosity. Glass beads (2mm diameter) were dropped with a variety of impact velocities into the glycerol solutions. The impact and the resulting splash were recorded using a high-speed camera (Olympus iSPEED 2) at 8000 frames per second. These tests indicated that different viscosities result in different threshold velocities at which the jet splash profile becomes apparent. We are reporting different methods of enrichment of whole blood in order to induce controlled changes in the viscosity of the samples that mimic physiological processes. We have adapted existing methods for enrichment of red blood cell membranes with cholesterol to create a condition known as “spur” red cells which is known to cause a decrease in red cell deformability, altering the visco-elastic properties of the cell (M. Shinitzky, FEBS Letters, 85, 317–320). The splash diagnostic test will be applied to these samples to determine the changes in viscosity resulting from the enrichment. Ultimately, we will test blood samples from leukemia patients at different stages of treatment to further improve the ability of the splash test to be used in a clinical environment. Citation Information: Cancer Res 2009;69(23 Suppl):C70.
EVOLUTION OF THE FETAL ATRIOVENTRICULAR (AV) INTERVAL FROM 6-40 WEEKS OF GESTATION
Authors: Dora Gyenes, Joseph Atallah, Jesus Serrano, C. Monique Bohun, Lisa Howley, Angela McBrien, Winnie Savard, Venu Jain, Tarek Motan, Lisa Hornberger
Journal: Journal of the American College of Cardiology (2016)
PWE-123 Undergraduate Understanding Of Identification And Brief Advice For Alcohol Disorders
Authors: A Patel, K Richardson, J Hough, A Cairns
Journal: Gut (2014)

<h3>Introduction</h3> The number of deaths in England due to liver disease is rising. The North West has the highest rate of alcohol related deaths for men and women.<sup>1</sup> Brief interventions can reduce harmful drinking<sup>2</sup> and therefore have the potential to contribute to reducing the burden of liver disease. There is a recognition that all health professionals must strive to detect risk factors for liver disease and intervene early to manage them. <sup>3</sup> Do the next generation of doctors know this? <h3>Methods</h3> A short survey was completed by 100 Manchester medical students in clinical placements to assess their knowledge of identification and brief advice (IBA), its effectiveness in comparison to smoking cessation advice and their knowledge of which particular patients benefit most from its use. <h3>Results</h3> 96% of the students involved in the survey had not heard of IBA. Once IBA was explained 21.1% thought that it would be less effective than smoking cessation advice. Only 47% of the students correctly thought that increasing risk drinkers were the group that would benefit most rather than higher risk or dependent drinkers. <h3>Conclusion</h3> The vast majority of the students involved in the survey were not aware of IBA. A significant number underestimated its impact and there was confusion about which patients would benefit. This is despite the students all being in clinical placements in the North West of England The unfamiliarity of these students to IBA may well be a reflection of its limited use in day to day practice by their supervising clinicians. Despite the recognition of its importance there may be a long way to go in making identification and brief advice routine practice for our future doctors. <h3>References</h3> Burden of Liver Disease and Inequalities in the North West of England. Carl Benyon, Dan Hungerford. North West Public Health Observatory National Institute for Health and Clinical Excellence. Alchol Use Disorders: Diagnosis, assessment and management of harmful drinking and alcohol dependence. (Clinical Guideline CG115.) 2011 Neeraj Bhala, Guruprasad Aithal, James Ferguson. How to tackle rising rates of liver disease in UK. <i>BMJ</i> 2013;346 <h3>Disclosure of Interest</h3> None Declared.
Abstract 4863: Pathway-focused cancer mutation profiling with somatic mutation PCR arrays
Authors: Samuel Long, Min You, Liang Wang, Xiaofang Jiang, Jie Cheng, Yexun Wang
Journal: Cancer Research (2011)

Abstract Recent advances in sequencing technologies have led to significant increases in the number of known cancer somatic mutations. Translating such information into therapeutic benefits requires molecular characterization of all major human tumor types and the advent of research tools that enable interrogation of multiple mutations in multiple cancer genes simultaneously, with high accuracy and scalability. As an increasing number of important signal transduction pathways, such as the EGFR-RAS-RAF pathway, are implicated in a variety of cancers, the utility of pathway-focused mutation analysis arrays has increased. This study examined the use of real-time PCR somatic mutation detection arrays that target all known functionally important mutation sites within an entire signal transduction pathway. Each array contains 80 to 90 ARMS® primers and 5’ hydrolysis probe-based qPCR assays that allow simultaneous detection of the most frequent and functionally important mutations for multiple genes in a specific pathway. In this study, different cancer sample types (fresh-frozen or FFPE samples from cancer cell lines and tissues) were profiled on qPCR arrays. To establish methodology validity, pyrosequencing was used as a performance benchmark. FFPE tissue sections of lung adenocarcinoma originating from different sources and with dramatically different DNA quality were tested to examine the tolerance of qPCR-based mutation detection to sample quality variation. Finally, data analysis algorithms were developed to maximize the accuracy of mutation/genotype calls. Results indicated that allele-specific PCR amplification combined with probe detection can achieve sufficient analytical specificity and sensitivity for detecting as little as 1% mutant alleles in a background of wild type genomic DNA. In addition, the method can detect mutations in FFPE samples over a wide range of quality (i.e. with differing extents of DNA degradation), and the mutations detected were verified by pyrosequencing analysis. Interestingly, multiple mutations across different genes within the EGFR pathway, and more than one mutation within the EGFR gene, were detected in lung adenocarcinoma samples, indicating either acquisition of multiple mutations by the same cell population or sample heterogeneity. In conclusion, it was demonstrated that somatic mutation profiling in the context of a pathway can be easily accomplished by using qPCR arrays and can be applied to biomarker development for a variety of human cancers. Disclaimer: The applications presented here are for research use only. Not for use in diagnostic procedures. 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 4863. doi:10.1158/1538-7445.AM2011-4863
Confocal laser endomicroscopy for the differential diagnosis of ulcerative colitis and Crohn’s disease: a pilot study
Authors: Gian Tontini, Jonas Mudter, Michael Vieth, Raja Atreya, Claudia Günther, Yurdagül Zopf, Dane Wildner, Ralf Kiesslich, Maurizio Vecchi, Markus Neurath, Helmut Neumann
Journal: Endoscopy (2014)

<b>Background and study aim:</b> The differential diagnosis of ulcerative colitis from Crohn's disease is of pivotal importance for the management of inflammatory bowel diseases, as both entities involve specific therapeutic management strategies. Confocal laser endomicroscopy (CLE) allows on-demand, in vivo characterization of architectural and cellular details during endoscopy. The aim of this study was to assess the efficacy of CLE to differentiate between ulcerative colitis and Crohn's disease. <b>Patients and methods:</b> This was a prospective study involving consecutive patients with a well-established diagnosis of ulcerative colitis or Crohn's disease who underwent colonoscopy with fluorescein-aided confocal imaging. <b>Results:</b> Overall, 79 patients were included (40 Crohn's disease, 39 ulcerative colitis). CLE findings in patients with Crohn's disease, showed significantly more discontinuous inflammation (87.5 % vs. 5.1 %), focal cryptitis (75.0 % vs. 12.8 %), and discontinuous crypt architectural abnormality (87.5 % vs. 10.3 %) than in ulcerative colitis (<i>P</i> < 0.0001). Conversely, ulcerative colitis was associated with severe, widespread crypt distortion (87.2 % vs. 17.5 % in Crohn's disease), decreased crypt density (79.5 % vs. 22.5 %), and frankly irregular surface (89.7 % vs. 17.5 %; <i>P</i> < 0.0001 for all comparisons). Statistically significant differences were not seen for heavy, diffuse lamina propria cell increase or mucin preservation. No granulomas were visible. Based on these findings, a CLE scoring system was developed that revealed excellent accuracy (93.7 %) when compared with the historical clinical diagnosis and the histopathological gold standard. <b>Conclusions:</b> CLE could visualize several disease-specific microscopic features, which are conventionally used in standard histopathology to differentiate between ulcerative colitis and Crohn's disease. However, because of the limited penetration depth of CLE, submucosal details or granulomas were not visible. The new scoring system may allow in vivo diagnosis of ulcerative colitis or Crohn's disease. Trial registered at ClinicalTrials.gov: NCT 02238665
Evaluation of Biliary Enterogastric Reflux With Tc-99m HIDA in Partial Situs Inversus
Authors: ORSOLON PIERGIUSEPPE, GIACOMUZZI FRANCESCO, MUSSOLIN LUIGI
Journal: Clinical Nuclear Medicine (1997)

Hepatobiliary imaging with Tc-99m-HIDA was performed on a 57-year-old woman with partial situs inversus. Scans showed reflux of radioactive material into the right side of the stomach.
Abstract 3379: Iron-deficient anemia promotes breast cancer growth and lung metastasis
Authors: Jinlong Jian, Qing Yang, Xi Huang
Journal: Cancer Research (2011)

Abstract Young breast cancer patients &amp;lt;45 years old are at a higher risk of dying from the disease than older patients. Specific risk factors contributing to this high mortality rate have not been identified. Iron deficient anemia (IDA) is a common ailment in young pre-menopausal women both in developed and developing countries. In the present study, we hypothesize that IDA promotes breast cancer growth and metastasis. To test this hypothesis, Balb/c mice were fed three levels of iron diets, 3.5 ppm Fe as iron deficient, 35 ppm as normal low, and 350 ppm as normal high for 12 wks. Consistent with previous literature reports, iron levels in diets ranging from 35 to 350 ppm, which were considered normal, did not lead to significant differences in serum iron and transferrin saturation rates. However, an iron level at 3.5 ppm in the diet caused an IDA in mice. After subcutaneously inoculating 4T1 mammary cancer cells into the flanks of mice fed different iron diets, mice with IDA condition have significant higher tumor volumes as compared to those with normal iron status (2922 + 161 mm3 in 3.5 ppm Fe group vs 1636 + 86 mm3 in 35 ppm Fe group and 1453 + 90 mm3 in 350 ppm Fe group). Lung metastasis was also higher in IDA mice with 22.8 + 0.9 nodules per lung lobule in 3.5 ppm vs 13.8 + 0.8 in 35 ppm and 13.6 + 0.9 in 350 ppm Fe. To elucidate molecular mechanisms of IDA in tumor growth and metastasis, levels of epithelial mesenchymal transition (EMT) markers, such as snail, slug and zeb1, were found to be significantly higher in tumor tissues isolated from IDA mice. When investigating signal pathways regulating EMT, it was found that Notch pathway, including Notch 2, 3, 4, and Notch ligands such as Jagged1, 2, were all induced by IDA. In contrast to Notch, transforming growth factor (TGF)-β and wingless-int (WNT) signal pathways, known to stimulate EMT, were not affected, suggesting that IDA-induced EMT is Notch pathway-specific. Since anemia causes hypoxia, the expression of HIF-1α, a key transcription factor controlling hypoxic responses, was also induced by IDA. Similarly, Notch signal pathway and EMT markers were higher after transfecting HIF-1α cDNA into 4T1 cells. These data show that IDA-mediated breast cancer growth and lung metastasis is through HIF-1α accumulation and activation of Notch and EMT. Our study suggests that identification of IDA as a poor prognostic factor and its clinical improvement as a potential cancer therapy could be significant to the high mortality rate of young breast cancer patients. This work is supported by R21 CA132684. 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 3379. doi:10.1158/1538-7445.AM2011-3379
PTSD in relation to dissociation in traumatized police officers
Authors: I V Carlier, R D Lamberts, A J Fouwels, B P Gersons
Journal: American Journal of Psychiatry (1996)

The assumed relationship between dissociation and symptoms of posttraumatic stress disorder (PTSD) was examined.From a group of police officers who had experienced a traumatic event, the authors assessed the chronic dissociative symptoms of 42 police officers with PTSD, 50 police officers with partial PTSD, and 50 police officers who experienced no PTSD symptoms after the trauma.Police officers with PTSD, as well as those with partial PTSD, exhibited significantly more dissociative symptoms than police officers without PTSD symptoms.The study shows that it is quite probable that PTSD and partial PTSD predict dissociation and not the other way around.