tbuckley/cabot-search huggingface dataset:
MECHANISMS OF HYPERTENSION FOLLOWING VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION: THE HYPAZ TRIAL
Authors: Lucy Yang, Adam McGeoch, Annette Hubsch, Parag Gajendragadkar, Carmel McEniery, Fraz Mir, Kaisa Maki-Petaja, Nicola Ramenatte, Gayathri Anandappa, Simon Bond, Ian Wilkinson, Duncan Jodrell, Joseph Cheriyan
Journal: Journal of the American College of Cardiology (2016)
SAT0460 Patient self-report joint count, rheumatoid arthritis disease activity index (RADAI), on a multidimensional health assessment questionnaire (MDHAQ) is informative in patients with rheumatic diseases other than rheumatoid arthritis:
Authors: I. Castrejon, Y. Yazici, T. Pincus
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A patient self-report joint count, rheumatoid arthritis disease activity index (RADAI),<sup>1</sup> is correlated significantly with tender and swollen joint counts performed by a health professional in rheumatoid arthritis (RA) patients<sup>2</sup>. The RADAI is included on the multidimensional health assessment questionnaire (MDHAQ), which is completed in many rheumatology settings by all patients with all diagnoses, as the same questionnaire is (logistically) most feasible. <h3>Objectives</h3> To analyze RADAI painful joint count scores in patients with diagnoses other than RA in usual care setting. <h3>Methods</h3> Each patient seen at an academic rheumatology site completes an MDHAQ at each visit, while waiting to see the doctor in the infrastructure of clinical care. The RADAI on the MDHAQ includes 8 bilateral specific joint groups: fingers, wrist, elbow, shoulder, hip, knee, ankle and toes, each scored from 0 ("no pain") to 3 ("severe pain") (total 0-48). A random visit of 465 patients was analyzed including 75 with SLE, 50 with gout, 53 with PsA, 113 with OA, as well as 174 with RA. Mean RADAI and % of patients scoring each specific joint group as affected were computed for each diagnosis, and compared to the MDHAQ patient global estimate (PATGL) and physician global estimate (DOCGL) using Spearman correlations. <h3>Results</h3> Patients were primarily women (68%), age 51±16 years;SLE patients were youngest (39.5±13.8) and OA patients oldest (62.8±12.5). An abnormal RADAI score &gt;0 was reported by 99% of patients with OA, 87% of patients with RA, 83% with PsA, 60% with gout, and 59% with SLE. The joints reported as most affected were knees (58%) and fingers (52%) in all patients; in RA, fingers (52%), wrists (58%), and knees (58%); in SLE, fingers (37%) and shoulders (32%); in gout, toes (24%) and knees (22%); in PsA, knees (43%) and fingers (40%), and in OA, knees (68%) and fingers (42%) (Table). RADAI scores were correlated significantly with PATGL (rho =0.50–0.75, p&lt;0.001), and moderately, though significantly, with DOCGL in all diagnoses except SLE (rho =0.40–0.54, p&lt;0.001). <h3>Conclusions</h3> A RADAI self-report joint count on an MDHAQ can be informative in patients with OA, gout, psoriatic arthritis and SLE, in addition to RA, with no additional work by the doctor, to assess clinical status in usual care. <h3>References</h3> Stucki G, Liang MH, Stucki S, Bruhlmann P, Michel BA. Arthritis Rheum 1995;38:795-8. Barton JL, Criswell LA, Kaiser R, Chen YH, Schillinger D. J Rheumatol 2009;36:2635-41. <h3>Disclosure of Interest</h3> None Declared
Increased FDG Uptake in the Right Cardiac Chambers in a Patient with Pulmonary Emphysema
Authors: Paulo S Duarte, Hongming Zhuang, Cristiano Machado, Flavia Aldighieri, Luiz R F Martins, Gilberto Alonso
Journal: Clinical Nuclear Medicine (2002)

DUARTE, PAULO S. M.D.*; ZHUANG, HONGMING M.D., Ph.D.†; MACHADO, CRISTIANO M.D.*; ALDIGHIERI, FLAVIA B.Sc.*; F. MARTINS, LUIZ R. M.D.*; ALONSO, GILBERTO M.D.* Author Information
PWE-255 5-ASA enhances<i>DUOX2</i>expression in active ulcerative colitis: a risk for colorectal cancer?
Authors: T Macfie, A Parker, A Nijhuis, T Boitsova, N Suraweera, R Jeffery, R Poulsom, J Lindsay, A Silver
Journal: Gut (2012)

<h3>Introduction</h3> Colonic <i>DUOX2</i> expression produces hydrogen peroxide, a reactive oxygen species (ROS), which is up-regulated in active ulcerative colitis (UC). Overproduction of hydrogen peroxide amplifies ROS-induced genetic damage and causes cellular transformation which may explain the increased colorectal cancer (CRC) risk associated with chronic UC. Mesalazine (5-ASA) has been shown to be chemo-preventative for UC associated CRC and scavenges ROS. Here, we aimed to identify and investigate the effect of 5-ASA on <i>DUOX2</i> expression using human rectal cancer cell lines and mucosal tissue biopsies. <h3>Methods</h3> Mucosal biopsies were taken from 35 patients with UC and 24 patients with normal colons for in vivo experiments, and 24 patients with UC and 14 patients with normal colons for ex vivo experiments. Total RNA was extracted and quantitative real-time PCR used to calculate expression of <i>DUOX2</i>. Cytometric bead array technology was used on ex vivo culture supernatants to measure cytokine profiles. In situ hybridisation for <i>DUOX2</i> expression was performed on sections from eight matched pairs of non-inflamed/inflamed biopsies and five matched pairs of non-inflamed/inflamed/dysplasia biopsies from UC patients. Human rectal cancer cells were used for quantitative real-time PCR, with multiparameter flow cytometry utilised to measure hydrogen peroxide levels, apoptosis, DNA damage and cell proliferation. <h3>Results</h3> <i>DUOX2</i> is expressed throughout the colonic epithelium, is upregulated in active compared to quiescent ulcerative colitis and also in areas of UC associated dysplasia. In the setting of intestinal inflammation, but not in quiescent disease, 5-ASA enhances <i>DUOX2</i> expression in vivo and ex vivo. As expected, 5-ASA was found to suppress cytokine (IL-6 and IL-8) production during an inflammatory flare and to maintain low cytokine levels during remission. The addition of 5-ASA in vitro led to upregulation of <i>DUOX2</i> and elevated levels of hydrogen peroxide, DNA damage and apoptosis. These effects were further enhanced in a setting of hypoxia. <h3>Conclusion</h3> We have shown that 5-ASA over stimulates <i>DUOX2</i> expression in the setting of inflammation and hypoxia, but not in quiescent disease. Importantly, this suggests that during a flare 5-ASA could act as a carcinogen rather than a chemo-preventative drug. Further investigations to confirm the functional relevance of <i>DUOX2</i> up-regulation in the colonic mucosa of patients with active UC is indicated. <h3>Competing interests</h3> T Macfie Grant/Research Support from: SHIRE, A Parker: None declared, A Nijhuis: None declared, T Boitsova: None declared, N Suraweera: None declared, R Jeffery: None declared, R Poulsom: None declared, J Lindsay Grant/Research Support from: SHIRE, A Silver: None declared.
Abstract 134: The regulatory role of microRNA 338-3p in malignant gliomas
Authors: Shawn Hervey-Jumper, Xiaobing He, Thant Zhu, Mikel Gurrea, Caroline Talsma, Jessica Crowley, Mark Costello, Callie Flack, Heth Jason, Karin Muraszko, Xing Fan
Journal: Cancer Research (2011)

Abstract Introduction: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Even with optimal therapy, more than 70% of GBM patients will die within 2 years of diagnosis. MicroRNAs (miR) are important regulators of gene expression through posttranscriptional silencing of target mRNA. MicroRNA roles in cell proliferation, invasion, angiogenesis, and glioma stem cell activity are little known. In this study, we focus on the expression and function of microRNAs in human gliomas. Methods: Using RNA extracted from 15 GBM patient samples and serum collected from 2 glioma patients, miR 338-3p expression, relative to normal brain and control serum, was examined using RT PCR. Regional miR expression within a single tumor was identified. A DNA fragment containing the hsa-miR-338-3p locus was amplified and cloned into a lentiviral vector, then transduced into GBM neurosphere lines. MicroRNA 338-3p and its downstream target, expression was assessed by RT PCR and western blot. GBM neurosphere growth was examined in vitro. Results: Over-expression in miR 338-3p is associated with decreased glioma cell proliferation and neurosphere formation. MicroRNA 338-3p shows decreased expression in the core of malignant gliomas with increased expression at the tumors rim and migrating edge. MiR 338-3p expression induces cleaved caspase 3 expression. MiR 338-3p targets Histone deacetylase 4 (HDAC4). Conclusion: MicroRNA 338-3p inhibits GBM neurosphere growth in vitro through reducing proliferation and inducing apoptosis possibly via targeting of HDAC4. 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 134. doi:10.1158/1538-7445.AM2011-134
Abstract 1500: Bone morphogenetic proteins stimulate mammary fibroblasts to promote mammary tumorigenesis
Authors: Philip Owens, Hannah Polikowsky, Michael W. Pickup, Lauren A. Matise, Agnes E. Gorska, Aubie K. Shaw, Sergey V. Novitskiy, Mary E. Aakre, Charles C. Hong, Harold L. Moses
Journal: Cancer Research (2012)

Abstract Bone Morphogenetic Proteins (BMPs) are secreted cytokines/growth factors belonging to the Transforming Growth Factor ≤ (TGFβ) superfamily. BMPs have recently been shown to be overexpressed in human breast cancers, however loss of BMP signaling in mammary carcinomas has also been shown to accelerate metastases. Stimulation of dermal fibroblasts with BMP4 can enhance pro-tumorigenic factors uniquely from the epidermal response. Additionally, treatment of carcinoma-associated fibroblasts (CAFs) derived from a mouse prostate carcinoma with BMP have been reported to stimulate tumor-associated angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts and determine their response during mammary tumor progression. We first identified secreted pro-inflammatory cytokines and matrix-metalloproteinases (MMPs) upregulated in response to BMP4 treatment. We found that fibroblasts stimulated with BMP4 could enhance tumor invasion, which was inhibited by a BMP receptor kinase antagonist. We next demonstrated that BMP signaling was specifically absent in the stroma of human ductal and lobular carcinoma in situ (DCIS &amp; LCIS). Yet after progression to invasion, breast tumors of many distinct subtypes contained a stroma active for BMP signaling. We further extended these observations with human normal mammary fibroblasts and compared them to human fibroblasts from breast cancer and found that BMP was capable of inducing MMP3 and IL-6 secretion in normal fibroblasts. However carcinoma associated fibroblasts had constitutively elevated levels of MMP3 and IL-6 that corresponded to enhanced BMP signaling in addition to loss of secreted BMP antagonists. These experiments demonstrate that BMP may play important tumor promoting functions within the tumor microenvironment. 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 1500. doi:1538-7445.AM2012-1500
Case 20-2003
Authors: Eric C. Larsen, Susan A. Connolly, Andrew E. Rosenberg
Journal: New England Journal of Medicine (2003)

Presentation of CaseA nine-year-old girl was admitted to the hospital because of hepatosplenomegaly and pain in the thigh.The patient had been well until three years earlier, when she began to have frequent episodes of epistaxis. Two years before admission, mild abdominal distention developed. Periodic examinations by her physician were reported to have revealed no abnormalities. Two months before admission, the abdominal distention worsened but was not accompanied by abdominal pain. Physical examination revealed hepatosplenomegaly. An abdominal ultrasonographic study confirmed the presence of hepatosplenomegaly, without evidence of portal-vein thrombosis (Figure 1). The results of liver-function tests were normal or . . .
Early Treatment with Ganciclovir to Prevent Cytomegalovirus Disease after Allogeneic Bone Marrow Transplantation
Authors: James M. Goodrich, Motomi Mori, Curt A. Gleaves, Charles Du Mond, Monica Cays, Darlene F. Ebeling, William C. Buhles, Bernadette DeArmond, Joel D. Meyers
Journal: New England Journal of Medicine (1991)

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir for the early treatment of CMV infection in asymptomatic recipients of bone marrow transplants whose surveillance cultures for CMV became positive.
Book Review Let's Talk: An Honest Conversation on Critical Issues: Abortion, Euthanasia, AIDS, Health Care By C. Everett Koop and Timothy Johnson. 138 pp. Grand Rapids, Mich., Zondervan, 1992. $8.99. 0-310-59781-1
Authors: Marcia Angell, Lara Goitein
Journal: New England Journal of Medicine (1993)
Abstract 97: Chronic nicotine and NNK exposure causes promoter hypermethylation of GAD2 in human pancreatic duct epithelial cells
Authors: Heike Bernert, Howard K. Plummer, Hildegard M. Schuller
Journal: Cancer Research (2011)

Abstract Epigenetic alterations are present at early stages of carcinogenesis, and DNA promoter hypermethylation in precursor lesions potentially affects transcriptional regulation. Previous studies by our laboratory have shown that the inhibitory neurotransmitter γ-aminobutyric acid (GABA) inhibits the proliferation of human pancreatic cancer cells grown both in vitro and in mouse xenografts. To test the hypothesis that nicotine as well as the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induce changes in methylation status of the GABA synthesizing enzymes GAD1 (GAD67) and GAD2 (GAD65), the human pancreatic duct epithelial cell line clone HPDE6-E6E7c7 has been exposed to daily treatment of either nicotine or NNK over a course of five days. This initial screen of the methylation status of the promoter region of GAD1 and GAD2 by bisulfate genomic sequencing in HPDE6-E6E7c7 indicates aberrant methylation of GAD2 by either nicotine or NNK. Quantitative methylation-specific PCR as well as gene expression studies by real-time PCR after 5-aza-2’-deoxycytidine treatment, alone or in combination with trichostatin A on the last day of treatment along with concurrent five day treatment with nicotine or NNK confirm these observations that aberrant methylation of GAD2 may be an important factor in the pathogenesis of pancreatic cancer. Quantitative methylation-specific PCR indicates aberrant methylation in six out of ten human matched normal versus cancerous pancreatic tissue samples, which corroborates the in vitro results. In conclusion, exposure to nicotine and NNK leads to significant epigenetic alterations of the GAD2 promoter region. Consecutive silencing of GAD2 with suppression of GABA synthesis may represent an important mechanism by which nicotine and related compounds induce disturbances in inhibitory neurotransmitter circuits which may contribute to the pathogenesis of ductal adenocarcinoma of the pancreas. Supported by grants 1RO1CA130888 and 2RO1CA042829 with the National Cancer Institute. 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 97. doi:10.1158/1538-7445.AM2011-97
FRI0163 Survival of the second biologic after the first anti-tnf failure in the treatment of rheumatoid arthritis: data from biorx.si registry
Authors: Ž. Rotar, M. Tomšič
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current recommendations for management of RA propose an 0anti-TNF agent for patients failing to achieve the treatment target with synthetic DMARDs. If 1<sup>st</sup> anti-TNF fails, a different anti-TNF, abatacept, rituximab (RTX) or tocilizumab (TCZ) are equally recommended.<sup>1</sup> It has been shown that non anti-TNF agents are at least as effective as the anti-TNF. Little is known about the survival of 2<sup>nd</sup> biologic agents, especially RTX and TCZ. <h3>Objectives</h3> To investigate the survival of the 2<sup>nd</sup> biologic after switching from the 1<sup>st</sup> anti-TNF agent. <h3>Methods</h3> Data was extracted from the Slovenian registry (BioRx.si) on Dec 15<sup>th</sup>, 2012. Kaplan Meier survival analysis was performed. Statistical significance was determined with the Log-Rank and Wilcoxon tests. <h3>Results</h3> 688 RA patients (81.5% female, mean age at diagnosis 45.2±11.8 years, 81.8% RF positive, 77% ACPA positive, concomitant methotrexate (MTX) 71.1%, leflunomide (LEF) 10.5%, metilprednisolone (MP) 45.3%, mean DAS28ESR 6.4±1.0) were treated using adalimumab, etanercept, infliximab, certolizumab, and golimumab in 43.6%, 30.7%, 10.7%, 9.9%, and 5.1% as the first biologic, respectively. Median survival of the first anti-TNF was 184 weeks. 242 (35.2%) patients (81.8% female, mean age at diagnosis 45.4±11.4 years, 81.8% RF positive, 77.6% ACPA positive; concomitant MTX 62.8%, LEF 12.4%, MP 47.1%; mean DAS28ESR 6.3±1.1) were switched to a different anti-TNF (55%), rituximab (14%) or tocilizumab (31%). Kaplan Meier survival curves for 2<sup>nd</sup> anti-TNF (as a group), RTX and TCZ are presented (Image). 2<sup>nd</sup> anti-TNF failed due to insufficient efficacy in 90%, and adverse events in 8%. <h3>Image/graph</h3> <h3>Conclusions</h3> After the 1<sup>st</sup> anti-TNF's failure, a 2<sup>nd</sup> anti-TNF is more likely to fail earlier than RTX or TCZ (p=0.000). There is a trend of better survival of RTX vs TCZ, which did not reach statistical significance (p=0.057). <h3>References</h3> Smolen JS, et al. Ann Rheum Dis. 2010;69:964-75. <h3>Disclosure of Interest</h3> None Declared
Abstract 162: Profiling of microRNA in oral cancer cells identifying miR-10b functions in oncogenesis and up-regulates in plasma of oral cancer patients
Authors: Ya-Ching Lu, Ann-Joy Cheng
Journal: Cancer Research (2011)

Abstract Oral cancer is the 6th leading cancer, and is still increasing with years. Since this cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact of family and society. MicorRNAs (miRNAs) are endogenous, non-coding small RNA, which consist of 21-23 nucleotides. They serve widespread functions as regulatory molecules in post-transcriptional gene silencing for the regulation of cellular bio-functions. And the dysregulation of miRNAs has been implicated in malignancy. Agilent system was used to perform miRNA profiling in 6 cancer cell lines and 5 lines of normal keratinocytes for identification of differently expressed miRNAs. There were 23 miRNAs selected as candidates which were shown more than 2-fold change with the FDR&amp;lt;0.1. Among these miRNAs, 19 of them were elevated and 4 were decreased in oral cancer cell lines. miR-10b was validated by qPCR analysis showed significantly up-regulated in cancer cells. Furthermore, the biological function of miR-10b was investigated after alteration of miR-10b expression. Reduction of miR-10b by antisense oligonucleotide further resulted in retard of cell migratory and invasive ability, however, no significant alterations on cell growth or chemo/radio-sensitivity. In analyzing miR-10b expression in 24 normal and 29 plasma samples from oral cancer patients, miR-10b was up-regulated 3.3 fold in the cancer patients (P&amp;lt;0.0001). Taken together, miR-10b plays a role in the carcinogenesis through promoting cancer cell migratory and invasive function, and plasma miR-10b may serve as a biomarker for oral cancer patients. 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 162. doi:10.1158/1538-7445.AM2011-162
Case 6-2012
Authors: Tracey A. Cho, Mykol Larvie, Di Tian, Mari Mino-Kenudson
Journal: New England Journal of Medicine (2012)

A 45-year-old man with a history of alcoholism was admitted to the hospital because of cognitive decline and jaundice. He had a 3-month history of cough, blood-tinged sputum, and vomiting. Imaging showed a peripherally enhancing brain lesion. A diagnostic procedure was performed.
A new method for endoscopic variceal band ligation in Zenker’s diverticulum
Authors: Fatih Tekin, Ilker Turan, Omer Ozutemiz
Journal: Endoscopy (2015)

A 62-year-old man was admitted with hematemesis. He had been diagnosed to have hepatitis B-related cirrhosis 4 months earlier, and had not undergone esophagogastroduodenoscopy (EGD) previously. He had no history of dysphagia. During intubation with an endoscope (GIF Q-150, Olympus, Japan), resistance was encountered at the upper esophageal sphincter, and a diverticulum was noted at this level. Although very difficult, the endoscope was passed gently into the esophagus. EGD was performed and esophageal varices with red spots were diagnosed. Endoscopic variceal ligation (EVL) was decided; however we considered that repeated esophageal intubation would be impossible with an affixed band ligation set. Thus, a guidewire (0.035 inch; Boston-Scientific, Marlborough, MA, United States) was inserted into the stomach via the working channel under endoscopic vision, and the endoscope was withdrawn over the guidewire. An endoscopic band ligator device (Speedband Superview Super 7 Multiple Band Ligator, Boston-Scientific) was fixed to the endoscope. Following that, the endoscope was loaded with a catheter (standard type catheter, Boston-Scientific) beside the handle of the multiple band ligator ([Fig. 1]). Thereafter, the guidewire was inserted into the leading end of the catheter and pushed until it passed out from the working channel of the endoscope. The catheter was first advanced to the stomach. The endoscope was then pushed forward over the catheter into the distal esophagus ([Fig. 2]). After complete withdrawal of both catheter and guidewire, EVL was performed successfully. The second EVL session was carried out using the same method 4 weeks later.
Monitoring Health Outcomes of Assisted Reproductive Technology
Authors: Dmitry M Kissin, Denise J Jamieson, Wanda D Barfield
Journal: New England Journal of Medicine (2014)

To the Editor: During the past 35 years, assisted reproductive technology has been transformed from a miracle to a standard and common part of medical practice. Although this technology is believed to be safe and has resulted in more than 5 million infants born globally, rapid technological progress leading to treatment modifications makes it important to continually monitor the safety of assisted reproductive technology for the rapidly growing population of users of the technology and infants conceived with its use. Although many countries have national registries to monitor the use and effectiveness of assisted reproductive technology, they are typically not . . .