tbuckley/cabot-search huggingface dataset:
Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity
Authors: Carlos Galán-Arriola, Manuel Lobo, Jean Paul Vílchez-Tschischke, Gonzalo J. López, Antonio de Molina-Iracheta, Claudia Pérez-Martínez, Jaume Agüero, Rodrigo Fernández-Jiménez, Ana Martín-García, Eduardo Oliver, Rocío Villena-Gutierrez, Gonzalo Pizarro, Pedro L. Sánchez, Valentin Fuster, Javier Sánchez-González, Borja Ibanez
Journal: Journal of the American College of Cardiology (2019)

Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.
Pink Disease
Authors: T. N. Fisher
Journal: BMJ (1947)

4. Radio-phosphorus is of no value in the treatment of acute leukaemias or of monocytic leukaemia.5. " Hodgkin's disease, lymphosarcoma, reticulum-cell sarcoma, and multiple myeloma do not respond as favourably to P`as they do to x-radiation."6.The limited evidence available suggests that radiophosphorus is not likely to prove to be a satisfactory agent for the treatment, of carcinoma of the breast, malignant melanoma, lympho-epithelioma, Ewing's tumour, or mycosis fuqgoides.
Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the Global Phase 3 INO-VATE Trial: Efficacy and Safety By Baseline CD22 Expression Level
Authors: Hagop M. Kantarjian, Wendy Stock, Ryan D. Cassaday, Daniel J. DeAngelo, Elias J. Jabbour, Susan M. O'Brien, Matthias Stelljes, Tao Wang, Luisa Paccagnella, Kevin Nguyen, Barbara Sleight, Erik Vandendries, A. Douglas Laird, Anjali S. Advani
Journal: Blood (2017)
Abstract 137: Quantitative Post--Cardiac Arrest Audiovisual Debriefing Improves Resuscitation Quality
Authors: Heather A Wolfe, Robert M Sutton, Jessica Leffelman, Dana E Niles, Lori Boyle, Rita Giordano, Daniela Davis, Margaret Priestley, Robert A Berg, Vinay M Nadkarni
Journal: Circulation (2012)

Introduction: American Heart Association (AHA) targets of high quality CPR are associated with improved survival. We previously identified deficiencies in CPR quality in our ICU, despite CPR refres...
Ліпідний спектр крові при хронічному панкреатиті за коморбідності з ішемічною хворобою серця: можливості корекції
Authors: T.M. Khrystych
Journal: GASTROENTEROLOGY (2014)

Мета дослідження. Оцінити значимість змін ліпідного спектра крові у хворих на хронічний панкреатит з ішемічною хворобою серця в патогенезі коморбідності даних захворювань і в динаміці лікування полікозанолом. Матеріали і методи. Дослідження проведене серед 22 пацієнтів (із них 10 пацієнтів із хронічним панкреатитом та дисліпідемією і 12 хворих із коморбідністю хронічного панкреатиту та ішемічної хвороби серця при синдромі ХСН I–II A-Б стадії II–III функціонального класу) і серед 10 практично здорових осіб. Чоловіків було 13, жінок — 9, віком від 31 до 69 років. Пацієнтам двох груп додатково до протокольного лікування призначали полікозанол по 10 мг 1 раз під час вечері, курсом до 3 місяців. Для вивчення особливостей ліпідного спектра крові визначали рівень загального холестерину, холестерину ліпопротеїдів високої щільності, тригліцеридів (використовуючи реактиви фірми Lachema (Чехія), методом Златікс — Зака). Рівень холестерину ліпопротеїдів низької щільності визначали за допомогою розрахункового методу за формулою Фрідевальда (Friedewald) з урахуванням того, що концентрація тригліцеридів не перевищувала 4,5 ммоль/л. Крім цього, визначали холестерин ліпопротеїдів дуже низької щільності та індекс атерогенності, використовуючи загальноприйняті розрахункові методи. Результати. У хворих із поєднаним перебігом хронічного панкреатиту з ішемічною хворобою серця в більшості випадків має місце вірогідне (р &lt; 0,05) підвищення показників загального холестерину, ліпопротеїдів низької і дуже низької щільності, тригліцеридів. При аналізі типів дисліпідемій встановлено, що частіше зустрічалися ІІа і ІІв типи (22 і 25 % відповідно), але при коморбідності частіше виявлявся ІІа і ІV тип дисліпідемій. У динаміці тримісячного лікування полікозанолом у хворих на хронічний панкреатит вірогідно підвищувалися показники холестерину ліпопротеїдів високої щільності і знижувалися показники тригліцеридів, що свідчить про гіполіпідемічний ефект препарату і про можливість використання його в поєднанні зі статинами з метою зменшення ризику кардіоваскулярних подій. Висновок. Коморбідність хронічного панкреатиту з ішемічною хворобою серця підвищує ризик прогресування дисліпідемії та атеросклерозу. Підтвердженням цього є підвищений індекс атерогенності у даній групі пацієнтів поряд із вираженістю порушень ліпідного спектра крові. Додаткове до курсового лікування призначення полікозанолу хворим із хронічним панкреатитом та дисліпідемією, а також у поєднанні з ішемічною хворобою серця сприяє зниженню і нормалізації деяких показників ліпідного спектра крові. Це дозволяє рекомендувати препарат для тривалого лікування даних груп пацієнтів, у тому числі в поєднанні зі статинотерапією.
Genomics and pharmacogenomics analyses of cancer cell lines using the CellMinerCDB and CellMiner web-applications
Authors: W. Reinhold, Y. Pommier
Journal: Annals of Oncology (2019)

Background: Complimentary datasets and functionality that facilitate comparisons of genomic, molecular and pharmacological data within the NCI-60 cancerous cell lines, Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC), Cancer Therapeutics Response Portal (CTRP), NCI/DTP small cell lung cancer (SCLC), and NCI Almanac cell line sets are provided by the CellMiner (http://discover.nci.nih.gov/cellminer) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-applications. Methods: Pharmacogenomics analyses using CellMiner compare the 60 cancerous cell lines of the NCI-60 using five tools, and include 22 data sets. Pharmacogenomics analyses using CellMinerCDB compare the NCI-60, CCLE, GDSC, CTRP, NCI/DTP SCLC, and NCI Almanac cell line data six, using eight tools, and include 29 data sets. Both provide multiple ways to download or query that data, and are described in detail in their respective urls. Results: Data for the NCI-60, providing the most extensive public set of cell line molecular and drug activity data (generated by the NCI Developmental Therapeutics Program https://dtp.cancer.gov), are made available through CellMiner. The substantially increased cell line numbers and tissue of origin types provided by the CCLE, GDSC, and CTRP are contained in CellMinerCDB. Separate but complimentary functionalities are provided by the two web-applications. Variable numbers and kinds of data types are available for the differing cell line sets. The composition and numbers of cell lines also varies within the different sets, with 60 for the NCI-60, 69 for the SCLC, and ∼1000 for the CCLE, GDSC, and CTRP. One may fill in data gaps by merging data from multiple sources, taking advantage of the partial cell line overlaps that exist between many of these cell line sets. Extended analysis and quality assessment are also made possible by comparisons of data from multiple institutions. Conclusions: Exploration of the relationships between and among molecular alterations and pharmacological responses in cancer cell lines from the omic perspective is facilitated by this rich set of data and functionalities. Legal entity responsible for the study: The National Cancer Institute, USA. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. National Institutes of Health 10.13039/100000002
Molecular Imaging of Factor XIII Activity for the Early Detection of Mouse Coronary Microvascular Disease
Authors: Zhen W. Zhuang, Yang Huang, Rong Ju, Mark W. Maxfield, Yongming Ren, Xiangning Wang, Xinlu Wang, Mitchel R. Stacy, John Hwa
Journal: Theranostics (2019)

Coronary microvascular disease (MVD) remains a major clinical problem due to limited mechanistic understanding and a challenging diagnosis. In the present study we evaluated the utility of targeted imaging of active factor XIII (FXIII) for detection of coronary MVD associated with thrombus. We hypothesized that a high specificity and sensitivity FXIII targeted radiolabeled probe can serve as a biomarker for cross-linked thrombi in the microvasculature, and thus an indicator for underlying coronary MVD. To evaluate this approach, a coronary MVD model was established for local induction of singlet oxygen and reactive oxygen species (ROS) via a photochemical reaction (PCR). Methods: PCR was used to induce endothelial injury and microthrombi via focal over-production of ROS only in the coronary microvasculature. Oxidative stress was initially evaluated in primary coronary endothelial cells to optimize parameters of PCR, which were then translated to in vivo experiments. To develop the coronary MVD model, 64 mice were assigned to one of four groups after thoracotomy: 1) sham control; 2) rose bengal; 3) green light; or 4) their combination. Following interventions, the mice underwent transmission electron microscopy, fluorescent myocardial perfusion, coronary angiography, and immunohistochemical staining. Echocardiography (n = 12) and gene expression (n = 10) studies were also performed after MVD induction to monitor serial changes in cardiac function and explore possible mechanisms. To diagnose early onset MVD, FXIII radioactivity was assessed in 104 mice using ex vivo gamma well counting (GWC) and in 14 mice using in vivo serial single photon emission computed tomography / computed tomography (SPECT/CT) imaging of a FXIII targeted technetium-labeled probe (99mTc-NC100668). Results:In vitro experiments demonstrated that photosensitizer concentration and light illumination time were critical parameters for PCR. In vivo experiments demonstrated manifestations of clinical MVD, including endothelial damage, a "no flow zone," arteriole rarefaction with patent epicardial coronary arteries, infiltration of inflammatory cells in the PCR-treated region, and preserved cardiac function. Gene expression also demonstrated a pro-thrombotic and impaired fibrinolytic status. In the early stages of MVD, enhanced FXIII activity was confirmed within the MVD region using GWC and in vivo SPECT/CT imaging. Conclusion: Our results demonstrate that molecular imaging of FXIII activity may allow for early detection of coronary MVD associated with thrombus, in a novel pre-clinical model.
NPC1L1‐Targeted Cholesterol‐Grafted Poly(β‐Amino Ester)/pDNA Complexes for Oral Gene Delivery
Authors: Yuan Liu, Dan Chen, Jialin Li, Dengning Xia, Miaorong Yu, Jinsong Tao, Xinxin Zhang, Li Li, Yong Gan
Journal: Advanced Healthcare Materials (2019)

Abstract Gene vectors for oral delivery encounter harsh conditions throughout the gastrointestinal tract, and the continuous peristaltic activity can quickly remove the vectors, leading to inefficient intestinal permeation. Therefore, vectors have demanding property requirements, such as stability under various pH and, more importantly, efficient uptake in different intestinal segments. In this study, a functional polymer, cholesterol‐grafted poly(β‐amino ester) (poly[hexamethylene diacrylate‐β‐(5‐amino‐1‐pentanol)] (CH‐PHP)), is synthesized and electrostatically interacted with plasmid DNA to form a CH‐PHP/DNA complex (CPNC). This complex is designed to target the Niemann–Pick C1‐like receptor, a cholesterol receptor, to improve oral gene delivery efficacy. With the presence of cholesterol, CH‐PHP shows mitigated cytotoxicity, enhanced enzyme resistance, and improved gene condensing ability. CPNC further contributes to ≈43.1‐ and 2.3‐fold increases in luciferase expression in Caco‐2 cells compared with PNC and Lipo 2000/DNA complexes, respectively. In addition, the in vivo transfection efficacy of CPNC is ≈4.1‐, 2.1‐, and 1.6‐fold higher than that of Lipo 2000/DNA complexes in rat duodenum, jejunum, and ileum, respectively. Therefore, CPNC may be a promising delivery vector for gene delivery, and using a cholesterol‐specific endocytic pathway can be a novel approach to achieve efficient oral gene transfection.
Case 81-1963
Authors: Harry Shwachman, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A seven-year-old boy was admitted to the hospital because of a chronic cough.The child had been well until a year and a half before admission, when he contracted pneumonia followed by rubeola; he was treated with tetracycline and recovered in three weeks. Thereafter, he had a cough that was worse in the morning and accompanied on rainy days by the production of grayish sputum without blood. Three weeks before admission the cough increased in severity, and the temperature was 99°F.; tetracycline therapy was begun. An x-ray film of the chest was reported to . . .
<i>Notes from the Field:</i> Identifying Risk Behaviors for Invasive Group A <i>Streptococcus</i> Infections Among Persons Who Inject Drugs and Persons Experiencing Homelessness — New Mexico, May 2018
Authors: Sandra J. Valenciano, Chelsea McMullen, Salina Torres, Chad Smelser, Almea Matanock, Chris Van Beneden
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In the spring of 2018, the New Mexico Department of Health contacted CDC about an increase in the number and prevalence of invasive group A Streptococcus infections reported through New Mexicoâs Active Bacterial Core surveillance system.
Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis
Authors: Anthony J. Comerota, Clive Kearon, Chu-Shu Gu, Jim A. Julian, Samuel Z. Goldhaber, Susan R. Kahn, Michael R. Jaff, Mahmood K. Razavi, Andrei L. Kindzelski, Riyaz Bashir, Parag Patel, Mel Sharafuddin, Michael J. Sichlau, Wael E. Saad, Zakaria Assi, Lawrence V. Hofmann, Margaret Kennedy, Suresh Vedantham
Journal: Circulation (2019)

Background: The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) previously reported that pharmacomechanical catheter–directed thrombolysis (PCDT) did not prevent postthrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis. In the current analysis, we examine the effect of PCDT in ATTRACT patients with iliofemoral deep vein thrombosis. Methods: Within a large multicenter randomized trial, 391 patients with acute deep vein thrombosis involving the iliac or common femoral veins were randomized to PCDT with anticoagulation versus anticoagulation alone (No-PCDT) and were followed for 24 months to compare short-term and long-term outcomes. Results: Between 6 and 24 months, there was no difference in the occurrence of PTS (Villalta scale ≥5 or ulcer: 49% PCDT versus 51% No-PCDT; risk ratio, 0.95; 95% CI, 0.78–1.15; P =0.59). PCDT led to reduced PTS severity as shown by lower mean Villalta and Venous Clinical Severity Scores ( P &lt;0.01 for comparisons at 6, 12, 18, and 24 months), and fewer patients with moderate-or-severe PTS (Villalta scale ≥10 or ulcer: 18% versus 28%; risk ratio, 0.65; 95% CI, 0.45–0.94; P =0.021) or severe PTS (Villalta scale ≥15 or ulcer: 8.7% versus 15%; risk ratio, 0.57; 95% CI, 0.32–1.01; P =0.048; and Venous Clinical Severity Score ≥8: 6.6% versus 14%; risk ratio, 0.46; 95% CI, 0.24–0.87; P =0.013). From baseline, PCDT led to greater reduction in leg pain and swelling ( P &lt;0.01 for comparisons at 10 and 30 days) and greater improvement in venous disease–specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life unit difference 5.6 through 24 months, P =0.029), but no difference in generic quality of life ( P &gt;0.2 for comparisons of SF-36 mental and physical component summary scores through 24 months). In patients having PCDT versus No-PCDT, major bleeding within 10 days occurred in 1.5% versus 0.5% ( P =0.32), and recurrent venous thromboembolism over 24 months was observed in 13% versus 9.2% ( P =0.21). Conclusions: In patients with acute iliofemoral deep vein thrombosis, PCDT did not influence the occurrence of PTS or recurrent venous thromboembolism. However, PCDT significantly reduced early leg symptoms and, over 24 months, reduced PTS severity scores, reduced the proportion of patients who developed moderate-or-severe PTS, and resulted in greater improvement in venous disease–specific quality of life. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00790335.
Living with vulval lichen sclerosus: a systematic review
Authors: S. Rees, L. Kirby, R.C. Simpson
Journal: British Journal of Dermatology (2019)

Lichen sclerosus (LS) is an under-researched disorder, particularly from the perspective of individuals who have the condition. A recent James Lind Alliance Priority Setting Partnership identified uncertainties in many aspects of the condition, including its impact on quality of life which was ranked within the ‘Top 10’ future research priorities.We set out to systematically review the qualitative literature exploring the lived experience of vulval LS (for the full protocol see PROSPERO ID:CRD42018106947). In PICO terms, the population was adults with vulval LS, there was no intervention nor comparator, and the outcomes were as follows. Firstly, we wanted to explore how LS affects various dimensions of everyday life and self-identity. Secondly, we wanted to explore the lived experience of the diagnosis and treatment. A better understanding of these issues will help healthcare providers to improve care, and enable researchers to identify key patient-focused research questions.
Gefitinib and erlotinib sensitivity in a panel of non-small cell lung cancer (NSCLC) cell lines
Authors: Michael J. Peyton, Luc Girard, Hisayuki Shigematsu, Shelley Sheridan, Debabrata Saha, Jon Kurie, Adi Gazdar, John D. Minna
Journal: Cancer Research (2005)

3389  Gefitinib and erlotinib are novel tyrosine kinase inhibitors (TKIs) with specificity for the epidermal growth factor receptor (EGFR) and are being used in the treatment of lung cancer. Recently mutations in the tyrosine kinase (TK) domain of EGFR have been associated with very high response rates and great sensitivity to gefitinib. However, another subset of lung cancer patients with wild-type EGFR in their tumors also have clinical benefit. We wished to develop gene expression profiles that predict responsiveness to gefitinib and erolotinib in lung cancers in addition to that conveyed by a TK domain EGFR mutation. To do this we determined the concentration of drugs required to give 50% growth inhibition (IC50) in a large panel of 45 NSCLC cell lines (8 with documented mutations of the TK domain of EGFR) which also were profiled for mRNA expression using Affymetrix U133 A & B chips. None of the lung cancer lines came from patients previously treated with TKIs. Cells were grown in 96-well plates, 24 hours after plating TKI’s were added to final concentrations from 0.06 μM to 1,000 μM in 4-fold dilutions, and at 96 hours after plating cell number was measured (CellTiter® 96 Aqueous One Solution (Promega) as a function of drug concentration (8 replicates per plate, all assays repeated 3 or more times), and the IC50 determined with software. Apoptosis assays were performed 24 hours after drug addition using the BD ApoAlert™ Caspase Plates (BD Biosciences). Nude mice were injected with 5 x 106 tumor cells subcutaneously into animals that received 350 cGy whole body irradiation. Tumors were measured twice weekly and tumor volume was calculated using the formula length x width2π/6. The IC50’s to gefitinib range from 0.04 to 324.37 μM and those to erlotinib range from 0.04 to 159.75 μM. As expected 5 of the EGFR mutant lung cancers were sensitive (IC50  1 μM). In apoptosis assays the 5 sensitive lines underwent large scale apoptosis while the 3 EGFR mutant but TKI resistant lines did not. There was nearly a perfect correlation between the log IC50 gefitinib versus the log IC50 erlotinib. The tumor cell lines with wild-type EGFR had IC50 values ranging from 1 μM to 300 μM) indicating a broad range of sensitivity within this group. Xenograft studies showed that sensitive cell lines were also exquisitely sensitive to gefitinib in vivo with large tumors being either cured or put into long term remission with TKI therapy while several resistant cell lines were resistant in vivo as well. Taken together these facts suggest that EGFR mutations are necessary but not sufficient to confer TKI sensitivity. These tumor cell lines provide novel resources to study these important aspects of targeted therapy. Likewise the xenograft studies provide a way to generate in vivo resistant variants to TKI therapy in EGFR mutant lung cancers.
Abstract P6-15-01: Withdrawn
Authors: S Loibl, M Untch, C Denkert, J Huober, JU Blohmer, E-M Grischke, J Furlanetto, H Tesch, C Hanusch, M Rezai, C Jackisch, WD Schmitt, G von Minckwitz, J Thomalla, S Kümmel, B Rautenberg, PA Fasching, K Rhiem, N Burchardi, A Schneeweiss
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Total Skeletal Muscle PGC-1 Deficiency Uncouples Mitochondrial Derangements from Fiber Type Determination and Insulin Sensitivity
Authors: Christoph Zechner, Ling Lai, Juliet F. Zechner, Tuoyu Geng, Zhen Yan, John W. Rumsey, Deanna Collia, Zhouji Chen, David F. Wozniak, Teresa C. Leone, Daniel P. Kelly
Journal: Cell Metabolism (2011)
Heart Disease and Stroke Statistics—2009 Update
Authors: Donald Lloyd-Jones, Robert Adams, Mercedes Carnethon, Giovanni De Simone, T. Bruce Ferguson, Katherine Flegal, Earl Ford, Karen Furie, Alan Go, Kurt Greenlund, Nancy Haase, Susan Hailpern, Michael Ho, Virginia Howard, Brett Kissela, Steven Kittner, Daniel Lackland, Lynda Lisabeth, Ariane Marelli, Mary McDermott, James Meigs, Dariush Mozaffarian, Graham Nichol, Christopher O'Donnell, Veronique Roger, Wayne Rosamond, Ralph Sacco, Paul Sorlie, Randall Stafford, Julia Steinberger, Thomas Thom, Sylvia Wasserthiel-Smoller, Nathan Wong, Judith Wylie-Rosett, Yuling Hong
Journal: Circulation (2009)