tbuckley/cabot-search huggingface dataset:
Fetal Hemodynamic Adaptive Changes Related to Intrauterine Growth
Authors: Bero O. Verburg, Vincent W.V. Jaddoe, Juriy W. Wladimiroff, Albert Hofman, Jacqueline C.M. Witteman, Eric A.P. Steegers
Journal: Circulation (2008)

Background— It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular changes in conditions of reduced fetal growth. The aim of the present study was to evaluate whether reduced fetal growth is associated with fetal circulatory changes and cardiac dysfunction. Methods and Results— This study was embedded in a population-based, prospective cohort study starting in early fetal life. Fetal growth characteristics and fetal circulation variables were assessed with ultrasound and Doppler examinations in 1215 healthy women. The fetal circulation was examined in relation to estimated fetal weight. Higher placental resistance indices were strongly associated with decreased fetal growth. Cerebral resistance showed a gradual decline with reduced fetal growth. Cardiac output, peak systolic velocity of the outflow tracts, and cardiac compliance showed a gradual reduction with diminished fetal growth, whereas intraventricular pressure gradually increased. Conclusions— Decreased fetal growth is associated with adaptive fetal cardiovascular changes. Cardiac remodeling and cardiac output changes are consistent with a gradual increase in afterload and compromised arterial compliance in conditions of decreased fetal growth. These changes have already begun to occur before the stage of clinically apparent fetal growth restriction and may contribute to the increased risk of cardiovascular disease in later life.
Bypass Surgery Versus Stenting for the Treatment of Multivessel Disease in Patients With Unstable Angina Compared With Stable Angina
Authors: P.J. de Feyter, P.W. Serruys, F. Unger, R. Beyar, V. de Valk, S. Milo, R. Simon, D. Regensburger, P.A. Crean, E. McGovern, P. van den Heuvel, C. van Cauwelaert, I. Penn, G.F.O. Tyers, W. Lindeboom
Journal: Circulation (2002)

Background — Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina. Recent improvements in percutaneous treatment (stent implantation) and bypass surgery (arterial grafts) warrant reevaluation of the relative merits of either technique in treatment of unstable angina. Methods and Results — Seven hundred fifty-five patients with stable angina were randomly assigned to coronary stenting (374) or bypass surgery (381), and 450 patients with unstable angina were randomly assigned to coronary stenting (226) or bypass surgery (224). All patients had multivessel disease considered to be equally treatable by either technique. Freedom from major adverse events, including death, myocardial infarction, and cerebrovascular events, at 1 year was not different in unstable patients (91.2% versus 88.9%) and stable patients (90.4% versus 92.6%) treated, respectively, with coronary stenting or bypass surgery. Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting (79.2% versus 78.9%) or bypass surgery (96.3% versus 96%) but was significantly higher in both unstable and stable patients treated with stenting (16.8% versus 16.9%) compared with bypass surgery (3.6% versus 3.5%). Neither the difference in costs between stented or bypassed stable or unstable angina ($2594 versus $3627) nor the cost-effectiveness was significantly different at 1 year. Conclusions — There was no difference in rates of death, myocardial infarction, and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients with stable angina. The rate of repeat revascularization of both unstable and stable angina was significantly higher in patients with stents.
Maximal aerobic power--a longitudinal analysis
Authors: David A. Brodie
Journal: British Journal of Sports Medicine (1987)

This is a well presented, compact colour atlas detailing the majority of rheumatological conditions which are amenable to photography.Each chapter begins with a resume of the condition under discussion followed by a mixture of clinical and X-ray pictures, each accompanied by an appropriate legend.The longest chapter deals with rheumatoid arthritis and emphasises the multi-system nature of this disease.The following chapter on juvenile chronic arthritis was the only disappointment, in that it utilised the term Still's disease more frequently than one would in clinical practice today.After dealing with inflammatory condition the author covers degenerative arthopathies, crystal arthopathies and connective tissues diseases.A picture of an LE cell is perhaps unnecessary since this test would now be obsolete in most laboratories but suppose may turn up in an examination situation.Rarer arthopathies and miscellaneous conditions are then covered.Generally the quality of the photographs is good, although a few of the X-rays have not been well reproduced.This book is recommended to fit in the pocket of any clinician, whatever their specialty or stage of career, and has the value of providing a spectrum of rheumatology that can be covered in a matter of minutes.
Targeting Hedgehog — a Cancer Stem Cell Pathway
Authors: Akil A. Merchant, William Matsui
Journal: Clinical Cancer Research (2010)

Abstract The Hedgehog (Hh) pathway has been implicated in a wide variety of human tumors, and early clinical trials with pathway antagonists have validated Hh signaling as a bona fide anticancer target. Despite these encouraging results, several issues surrounding the basic biology of the Hh pathway in human cancers remain unclear. These include the influence of specific oncogenic events on Hh signal transduction, the precise mode of Hh signaling (i.e., autocrine or paracrine) that occurs within human tumors, and the best means to inhibit aberrant pathway activity in the clinical setting. The cancer stem cell (CSC) hypothesis may explain a number of clinical phenomena, such as unchecked self-renewal and the development of metastatic disease, and to some extent, the Hh signaling pathway has been implicated in all of these processes. Therefore, Hh pathway inhibitors may also represent some of the first agents to formally examine the CSC hypothesis in the clinical setting. The diverse nature of Hh signaling in human cancers suggests that disease-specific factors must be carefully considered to identify the optimal use of novel pathway inhibitors. Clin Cancer Res; 16(12); 3130–40. ©2010 AACR.
Clinical phase I and pharmacokinetic study of S 16020, a new olivacine derivative: report on three infusion schedules
Authors: A. Awada, S. Giacchetti, B. Gerard, P. Eftekhary, C. Lucas, D. de Valeriola, M.G. Poullain, J. Soudon, C. Dosquet, M.-H. Brillanceau, B. Giroux, M. Marty, H. Bleiberg, F. Calvo, M. Piccart
Journal: Annals of Oncology (2002)
Mismatch Negativity Responses in Schizophrenia: A Combined fMRI and Whole-Head MEG Study
Authors: Tilo T.J. Kircher, Alexander Rapp, Wolfgang Grodd, Gerhard Buchkremer, Nikolaus Weiskopf, Werner Lutzenberger, Hermann Ackermann, Klaus Mathiak
Journal: American Journal of Psychiatry (2004)

Mismatch negativity is an event-related brain response sensitive to deviations within a sequence of repetitive auditory stimuli. It is thought to reflect short-term sensory memory and is independent of higher-level cognitive processes. Mismatch negativity response is diminished in patients with schizophrenia. Little is known about the mechanisms of this decreased response, the contribution of the different hemispheres, and its locus of generation.Patients with schizophrenia (N=12) and matched comparison subjects (N=12) were studied. A novel design to measure mismatch negativity responses to deviant auditory stimuli was generated by using the switching noises from the functional magnetic resonance imaging (fMRI) scanner, thus avoiding any interfering background sound. Stimuli included deviants of amplitude (9 dB lower) and duration (76 msec shorter) presented in a random sequence. The scanner noise was recorded and applied to the same subjects in a whole-head magnetoencephalography (MEG) device. Neuromagnetic and hemodynamic responses to the identical stimuli were compared between the patients and comparison subjects.As expected, neuromagnetic mismatch fields were smaller in the patient group. More specifically, a lateralization to the right for duration deviance was only found in comparison subjects. For the relative amplitude of the blood-oxygen-level-dependent signal (measured with fMRI), differences emerged in the secondary (planum temporale), but not primary (Heschl's gyrus), auditory cortex. Duration deviants achieved a right hemispheric advantage only in the comparison group. A significantly stronger lateralization to the left was found for the deviant amplitude stimuli in the patients.The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered interaction of regions within the superior temporal plane and across hemispheres could be in part responsible for language-mediated cognitive (e.g., verbal memory) and psychopathological (hallucinations, formal thought disorder) symptoms in schizophrenia.
Fast Measurement of Left Ventricular Mass With Real-Time Three-Dimensional Echocardiography
Authors: Victor Mor-Avi, Lissa Sugeng, Lynn Weinert, Peter MacEneaney, Enrico G. Caiani, Rick Koch, Ivan S. Salgo, Roberto M. Lang
Journal: Circulation (2004)

Background— Left ventricular (LV) mass is an important predictor of morbidity and mortality, especially in patients with systemic hypertension. However, the accuracy of 2D echocardiographic LV mass measurements is limited because acquiring anatomically correct apical views is often difficult. We tested the hypothesis that LV mass could be measured more accurately from real-time 3D (RT3D) data sets, which allow offline selection of nonforeshortened apical views, by comparing 2D and RT3D measurements against cardiac MR (CMR) measurements. Methods and Results— Echocardiographic imaging was performed (Philips 7500) in 21 patients referred for CMR imaging (1.5 T, GE). Apical 2- and 4-chamber views and RT3D data sets were acquired and analyzed by 2 independent observers. The RT3D data sets were used to select nonforeshortened apical 2- and 4-chamber views (3DQ-QLAB, Philips). In both 2D and RT3D images, LV long axis was measured; endocardial and epicardial boundaries were traced, and mass was calculated by use of the biplane method of disks. CMR LV mass values were obtained through standard techniques (MASS Analysis, GE). The RT3D data resulted in significantly larger LV long-axis dimensions and measurements of LV mass that correlated with CMR better ( r =0.90) than 2D ( r =0.79). The 2D technique underestimated LV mass (bias, 39%), whereas RT3D measurements showed only minimal bias (3%). The 95% limits of agreement were significantly wider for 2D (52%) than RT3D (28%). Additionally, the RT3D technique reduced the interobserver variability (37% to 7%) and intraobserver variability (19% to 8%). Conclusions— RT3D imaging provides the basis for accurate and reliable measurement of LV mass.
BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
Authors: Matthew S. Zabriskie, Christopher A. Eide, Srinivas K. Tantravahi, Nadeem A. Vellore, Johanna Estrada, Franck E. Nicolini, Hanna J. Khoury, Richard A. Larson, Marina Konopleva, Jorge E. Cortes, Hagop Kantarjian, Elias J. Jabbour, Steven M. Kornblau, Jeffrey H. Lipton, Delphine Rea, Leif Stenke, Gisela Barbany, Thoralf Lange, Juan-Carlos Hernández-Boluda, Gert J. Ossenkoppele, Richard D. Press, Charles Chuah, Stuart L. Goldberg, Meir Wetzler, Francois-Xavier Mahon, Gabriel Etienne, Michele Baccarani, Simona Soverini, Gianantonio Rosti, Philippe Rousselot, Ran Friedman, Marie Deininger, Kimberly R. Reynolds, William L. Heaton, Anna M. Eiring, Anthony D. Pomicter, Jamshid S. Khorashad, Todd W. Kelley, Riccardo Baron, Brian J. Druker, Michael W. Deininger, Thomas O’Hare
Journal: Cancer Cell (2014)
Response to Letters Regarding Article, “OMEGA, A Randomized, Placebo-Controlled Trial to Test the Effect of Highly Purified Omega-3 Fatty Acids on Top of Modern Guideline-Adjusted Therapy After Myocardial Infarction”
Authors: Bernhard Rauch, Rudolf Schiele, Steffen Schneider, Frank Diller, Norbert Victor, Helmut Gohlke, Martin Gottwik, Gerhard Steinbeck, Ulrike Del Castillo, Rudolf Sack, Heinrich Worth, Hugo Katus, Wilhelm Spitzer, Georg Sabin, Jochen Senges
Journal: Circulation (2011)
Myanmar ministers and opposition leaders agree plan to eliminate malaria by 2030
Authors: Anna Sayburn
Journal: BMJ (2015)

An “unprecedented” meeting of organisations from Myanmar has agreed the first stages of an ambitious plan to eliminate malaria from the country by 2030.

Three Myanmar government ministries—health, defence, and foreign affairs—met representatives of three of Myanmar’s ethnic minority communities and of the main opposition party, the National League for Democracy, at a conference held at the University of Maryland on 3 August.

The meeting came in the wake of gene sequencing research showing the emergence in Myanmar of malaria parasites with mutations making them resistant to the main treatment for the disease, artemisinin.1 It …
A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets
Authors: Sophia Adamia, Benjamin Haibe-Kains, Patrick M. Pilarski, Michal Bar-Natan, Samuel Pevzner, Herve Avet-Loiseau, Laurence Lode, Sigitas Verselis, Edward A. Fox, John Burke, Ilene Galinsky, Ibiayi Dagogo-Jack, Martha Wadleigh, David P. Steensma, Gabriela Motyckova, Daniel J. Deangelo, John Quackenbush, Richard Stone, James D. Griffin
Journal: Clinical Cancer Research (2013)

Despite new treatments, acute myeloid leukemia (AML) remains an incurable disease. More effective drug design requires an expanded view of the molecular complexity that underlies AML. Alternative splicing of RNA is used by normal cells to generate protein diversity. Growing evidence indicates that aberrant splicing of genes plays a key role in cancer. We investigated genome-wide splicing abnormalities in AML and based on these abnormalities, we aimed to identify novel potential biomarkers and therapeutic targets.We used genome-wide alternative splicing screening to investigate alternative splicing abnormalities in two independent AML patient cohorts [Dana-Farber Cancer Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes, France)] and normal donors. Selected splicing events were confirmed through cloning and sequencing analysis, and than validated in 193 patients with AML.Our results show that approximately 29% of expressed genes genome-wide were differentially and recurrently spliced in patients with AML compared with normal donors bone marrow CD34(+) cells. Results were reproducible in two independent AML cohorts. In both cohorts, annotation analyses indicated similar proportions of differentially spliced genes encoding several oncogenes, tumor suppressor proteins, splicing factors, and heterogeneous-nuclear-ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and spliceosome assembly. Our findings are consistent with reports for other malignances and indicate that AML-specific aberrations in splicing mechanisms are a hallmark of AML pathogenesis.Overall, our results suggest that aberrant splicing is a common characteristic for AML. Our findings also suggest that splice variant transcripts that are the result of splicing aberrations create novel disease markers and provide potential targets for small molecules or antibody therapeutics for this disease.
A Case of Severe Ebola Virus Infection Complicated by Gram-Negative Septicemia
Authors: Benno Kreuels, Dominic Wichmann, Petra Emmerich, Jonas Schmidt-Chanasit, Geraldine de Heer, Stefan Kluge, Abdourahmane Sow, Thomas Renné, Stephan Günther, Ansgar W. Lohse, Marylyn M. Addo, Stefan Schmiedel
Journal: New England Journal of Medicine (2014)

Ebola virus disease (EVD) developed in a patient who contracted the disease in Sierra Leone and was airlifted to an isolation facility in Hamburg, Germany, for treatment. During the course of the illness, he had numerous complications, including septicemia, respiratory failure, and encephalopathy. Intensive supportive treatment consisting of high-volume fluid resuscitation (approximately 10 liters per day in the first 72 hours), broad-spectrum antibiotic therapy, and ventilatory support resulted in full recovery without the use of experimental therapies. Discharge was delayed owing to the detection of viral RNA in urine (day 30) and sweat (at the last assessment on day 40) by means of polymerase-chain-reaction (PCR) assay, but the last positive culture was identified in plasma on day 14 and in urine on day 26. This case shows the challenges in the management of EVD and suggests that even severe EVD can be treated effectively with routine intensive care.
Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease
Authors: Carina Seidel, Øyvind Hjertner, Niels Abildgaard, Lene Heickendorff, Martin Hjorth, Jan Westin, Johan Lanng Nielsen, Henrik Hjorth-Hansen, Anders Waage, Anders Sundan, Magne Børset
Journal: Blood (2001)
Antibiotic resistance—the need for global solutions
Authors: Ramanan Laxminarayan, Adriano Duse, Chand Wattal, Anita K M Zaidi, Heiman F L Wertheim, Nithima Sumpradit, Erika Vlieghe, Gabriel Levy Hara, Ian M Gould, Herman Goossens, Christina Greko, Anthony D So, Maryam Bigdeli, Göran Tomson, Will Woodhouse, Eva Ombaka, Arturo Quizhpe Peralta, Farah Naz Qamar, Fatima Mir, Sam Kariuki, Zulfiqar A Bhutta, Anthony Coates, Richard Bergstrom, Gerard D Wright, Eric D Brown, Otto Cars
Journal: The Lancet Infectious Diseases (2013)
Estimating the Impact of Prehistoric Admixture on the Genome of Europeans
Authors: I. Dupanloup
Journal: Molecular Biology and Evolution (2004)

We inferred past admixture processes in the European population from genetic diversity at eight loci, including autosomal, mitochondrial and Y-linked polymorphisms. Admixture coefficients were estimated from multilocus data, assuming that most current populations can be regarded as the result of a hybridization process among four or less potential parental populations. Two main components are apparent in the Europeans' genome, presumably corresponding to the contributions of the first, Paleolithic Europeans, and of the early, Neolithic farmers dispersing from the Near East. In addition, only a small fraction of the European alleles seems to come from North Africa, and a fourth component reflecting gene flow from Northern Asia is largely restricted to the northeast of the continent. The estimated Near Eastern contribution decreases as one moves from east to west, in agreement with the predictions of a model in which (Neolithic) immigrants from the Near East contributed a large share of the alleles in the genome of current Europeans. Several tests suggest that probable departures from the admixture models, due to factors such as choice of the putative parental populations and more complex demographic scenarios, may have affected our main estimates only to a limited extent.
Mycobacteria and Crohn's disease.
Authors: S J Hampson, J J McFadden, J Hermon-Taylor
Journal: Gut (1988)

Mycobacteria and Crohn's diseaseRecent years have seen a resurgence of interest in the concept of a mycobacterial aetiology for Crohn's disease (CD)'and the possible use of antituberculous drugs in the condition has been rekindled by scattered case reports.'Mycobacterial associations with Crohn's disease have long been suspected7 -the histopathological picture clearly pointing a finger at the genus, but it is only in the last decade that mycobacteria have been isolated from CD tissue.' `They have also been isolated from ulcerative colitic and control tissue: this, however, should not come as a surprise.The Mvco- bacterium avium-intracellulare complex (MAIC) is a ubiquitous group of organisms which have recently become notable superinfections in AIDS.'This group and some fast growing mycobacteria appear to be saprophytic organisms and can be isolated from healthy individuals"' and the environ-
Multiple Organ Dysfunction Syndrome in Bone Marrow Transplantation
Authors: William D. Haire
Journal: JAMA (1995)

To define the frequency and outcome of organ dysfunction in bone marrow transplantation (BMT) and to determine if patients with organ dysfunction have lower levels of protein C (PC) and/or antithrombin III (ATIII) than those without organ dysfunction.Inception cohort of patients undergoing BMT, followed for 28 days, until hospital dismissal, or until death.Bone marrow transplant department of a university hospital.A total of 199 consecutive patients admitted for BMT.Standard supportive care was given to all patients.Definitions of organ dysfunction were arrived at prior to beginning the study. They include pulmonary, central nervous system (CNS), hepatic, and renal dysfunction. Protein C and ATIII levels were measured prior to beginning the preparative regimen and weekly thereafter.Single organ dysfunction, manifesting as pulmonary, CNS, or hepatic dysfunction, occurred in 93 (48.5%) of the 199 patients and was a strong predictor of multiple organ dysfunction syndrome (MODS) and death. Death occurred in 14 (7.0%) of the patients. Cause of death was precisely identified in only four patients. Low levels of either PC or ATIII were associated with death and pulmonary, CNS, and hepatic dysfunction. Multivariate analysis showed ATIII and PC levels were associated with single organ dysfunction independent of the type of transplant, the type of preparative regimen, and the presence of bacteremia.Single organ dysfunction during BMT is a marker for a systemic abnormality that has a high likelihood of progressing to MODS, similar to that seen in other critically ill patient populations. MODS is the leading cause of death in series of BMT patients. Low levels of ATIII and PC are markers of and may be involved in the pathogenesis of MODS in BMT.