tbuckley/cabot-search huggingface dataset:
Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis".
Authors: J C Reverter, S Béguin, H Kessels, R Kumar, H C Hemker, B S Coller
Journal: Journal of Clinical Investigation (1996)

The murine/human chimeric monoclonal antibody fragment (c7E3 Fab) blocks GPIIb/IIIa and alpha v beta 3 receptors, inhibits platelet aggregation, and decreases the frequency of ischemic events after coronary artery angioplasty in patients at high risk of suffering such events. Although inhibition of platelet aggregation is likely to be the major mechanism of c7E3 Fab's effects, since activated platelets facilitate thrombin generation, it is possible that c7E3 Fab also decreases thrombin generation. To test this hypothesis, the effects of c7E3 Fab and other antiplatelet agents were tested in a thrombin generation assay triggered by tissue factor. c7E3 Fab produced dose-dependent inhibition of thrombin generation, reaching a plateau of 45-50% inhibition at concentrations > or = 15 micrograms/ml. It also inhibited thrombin-antithrombin complex formation, prothrombin fragment F1-2 generation, platelet-derived growth factor and platelet factor 4 release, incorporation of thrombin into clots, and microparticle formation. Antibody 6D1, which blocks platelet GPIb binding of von Willebrand factor, had no effect on thrombin generation, whereas antibody 10E5, which blocks GPIIb/IIIa but not alpha v beta 3 receptors decreased thrombin generation by approximately 25%. Combining antibody LM609, which blocks alpha v beta 3 receptors, with 10E5 increased the inhibition of thrombin generation to approximately 32-41%. The platelets from three patients with Glanzmann thrombasthenia, who lacked GPIIb/IIIa receptors but had normal or increased alpha v beta 3 receptors, supported approximately 21% less thrombin generation than normal platelets. We conclude that thrombin generation initiated by tissue factor in the presence of platelets is significantly inhibited by c7E3 Fab, most likely in part through both GPIIb/IIIa and alpha v beta 3 blockade, and that this effect may contribute to its antithrombotic properties.
Abstract P5-02-03: Large-scale genomic instability consistently identifies BRCA1/2 inactivation in breast cancers
Authors: M-H Stern, T Popova, E Manié, T Dubois, B Sigal-Zafrani, M Bollet, X Sastre-Garau, A Vincent-Salomon, C Houdayer, D Stoppa-Lyonnet
Journal: Cancer Research (2012)

Abstract The goal of this study was to identify genomic markers predicting actual BRCA1/2 inactivation in breast cancers. By comparing genomic profiles of BRCA1/2 mutated and wildtype basal-like carcinomas (BLC) we developed a signature of BRCAness. The signature accounts for the level of the large scale genomic instability and was demonstrated to predict BRCA1/2 impairment with 100% sensitivity and 90% specificity in the large series of BLCs. We introduced a bioinformatics procedure evaluating the number of large scale rearrangements (denoted as Large Scale Transition or LST) in the genome and showed that the number of LSTs discriminate homologous recombination deficient and proficient tumors (Popova et al, Cancer Research 2012 Aug). The efficiency of the signature of BRCAness represented by the number of LSTs was then evaluated for the luminal breast tumors and ovarian carcinomas. Luminal breast tumors and ovarian carcinomas could be stratified into two groups according to the number of LSTs. The performance of the LST signature in all types of breast cancers will be presented. Measurement of LST is a highly reliable, simple and cost effective method to identify patients who should benefit of a BRCA1/2 testing, and to select tumors which may respond to treatment targeting DNA repair deficiencies (platinium salts, PARP inhibitors). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-02-03.
It Can Be Done
Authors: Robert C. Hood
Journal: Diabetes Care (2003)

Editor’s comment: After reading Dr. Hood’s results in an abstract for the 2003 American Diabetes Association (ADA) meeting, I invited him to write this letter. It serves to remind clinicians caring for diabetic patients that it can be done and to stimulate us to keep trying and to not be satisfied with less than the ADA’s evidence-based goals. 

The American Diabetes Association (ADA) has set standards of care that include various metabolic targets that are founded on evidenced-based medicine (1). Despite the widespread dissemination of these targets, many patients fail to obtain adequate control. There have been progressive developments in the understanding of type 2 diabetes and its attendant risk for both microvascular and macrovascular complications. With the host of new treatments available to the diabetes care team, the patient …
Impact of a baseline polymorphism on the emergence of resistance to the hepatitis C virus nonstructural protein 5a replication complex inhibitor, BMS-790052
Authors: Jin-Hua Sun, Donald R. O'Boyle, Yan Zhang, Chunfu Wang, Peter Nower, Lourdes Valera, Susan Roberts, Richard E. Nettles, Robert A. Fridell, Min Gao
Journal: Hepatology (2012)

The influence of naturally occurring polymorphisms on the potency of the HCV nonstructural protein 5A (NS5A) replication complex inhibitor, BMS-790052, was investigated by evaluating hybrid replicons in which the entire NS5A coding region of genotype (GT) la and 1b laboratory (lab) strains (H77c and Con1) were replaced with the corresponding regions of specimens collected from 10 GT-1a- and 6 GT-1b-infected subjects. For baseline (BL) specimens, with no previously observed resistance variants identified by population sequencing, the median 50% effective concentration (EC(50) ) values for BMS-790052 were similar for the clinically derived and lab strains. A Q30R variant was observed at viral breakthrough (VBT) in one of the GT-1a-infected subjects. Because the lowest plasma exposure of BMS-790052 observed in this subject was 117 nM and the median 50% effective concentration value for a GT-1a H77c replicon containing a Q30R substitution is ~7 nM, a rigorous investigation was initiated to determine the basis for resistance. Three approaches were used: (1) replacement of the entire H77c NS5A or (2) replacement of the N-terminal region of NS5A, with sequence from BL and day 14, and (3) substitution of specific amino acids. A BL polymorphism (E62D) did not contribute resistance to BMS-790052; however, the linked variant, Q30R-E62D, conferred high-level resistance in vitro and is likely responsible for VBT in vivo.Our data show that a BL polymorphism with minimal effect on the anti-HCV effect of BMS-790052 can affect the emergence of resistance and significantly affect clinical outcome. This work establishes a clear, systematic approach to monitor resistance to NS5A inhibitors in the clinic.
Hyperthermia‐Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy
Authors: Adolfo López‐Noriega, Conn L. Hastings, Burcin Ozbakir, Kathleen E. O'Donnell, Fergal J. O'Brien, Gert Storm, Wim E. Hennink, Garry P. Duffy, Eduardo Ruiz‐Hernández
Journal: Advanced Healthcare Materials (2014)

A novel drug delivery system, enabling an in situ, thermally triggered drug release is described, consisting of an injectable thermoresponsive chitosan hydrogel containing doxorubicin-loaded thermosensitive liposomes. The design, fabrication, characterization, and an assessment of in vitro bioactivity of this formulation is detailed. Combining on-demand drug delivery with in situ gelation results in a promising candidate for local chemotherapy. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
On Experiments in Medical Education
Authors: Carleton B. Chapman
Journal: New England Journal of Medicine (1977)

IT has been said that experiments in medical education always tend to revert, after initial enthusiasm has waned, to established patterns. The record, however, supports no such view. Perusal in detail of curriculum content and sequence, especially in the basic-science years, shows that since the forties there has been extensive experimentation and considerable permanent change. Early exposure to clinical problems, de-emphasis of gross morphology and updating of microbiology and biochemistry are some of the changes that have taken place all over the country.In addition to these changes and trends, some institutions have superimposed experiments of unusually sweeping design, and . . .
Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys
Authors: P. Magnus, J. J K Jaakkola
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To review repeated surveys of the rising prevalence of obstructive lung disease among children and young adults and determine whether systematic biases may explain the observed trends. <b>Design:</b> Review of published reports of repeated cross sectional surveys of asthma and wheezing among children and young adults. The repeated surveys used the same sampling frame, the same definition of outcome variables, and equivalent data collection methods. <b>Setting:</b> Repeated surveys conducted anywhere in the world. <b>Subjects:</b> All repeated surveys whose last set of results were published in 1983 or later. <b>Main outcome measures:</b> Lifetime and current prevalences of asthma and current prevalence of wheezing. The absolute increase (yearly percentage) in the prevalences of asthma and wheezing was calculated and compared between studies. <b>Results:</b> 16 repeated surveys fulfilled the inclusion criteria. 12 reported increases in the current prevalence of asthma (from 0.09% to 0.97% a year) and eight reported increases in the current prevalence of wheezing (from 0.14% to 1.24% a year). Changes in labelling are likely to have occurred for the reporting of asthma, and information biases may have occurred for the reporting of wheezing. Only one study reported an increase in an objective measurement. <b>Conclusions:</b> The evidence for increased prevalences of asthma and wheezing is weak because the measures used are susceptible to systematic errors. Until repeated surveys incorporating more objective data are available no firm conclusions about increases in obstructive lung disease among children and young adults can be drawn. <h3>Key messages</h3> There is an increase in the reporting of wheezing illness in children The increase may be due to information bias There is a lack of objective measurements in population based samples to support claims for an increase in asthma The changing informational content complicates following the epidemiology of asthma
Nuclear Imaging of Osteoma
Authors: Keisuke Enomoto, Hiroshi Nishimura, Kenichiro Hamada, Katsumi Doi, Takeshi Kubo, Jun Hatazawa
Journal: Clinical Nuclear Medicine (2008)

Osteomas are benign osteogenic tumors that arise from the proliferation of cancellous or compact bone. Osteomas are usually found in craniofacial bones. Surgery is indicated only when the lesions exhibit cosmetic changes, become symptomatic, or grow actively. The usefulness of Tc-99m MDP bone scintigraphy for osteoma has been reported previously. Herein, we report a 32-year-old woman with osteoma of the right temporal bone. Tc-99m MDP bone scintigraphy showed a typical uptake pattern at the tumor site, but no abnormal uptake was observed using F-18 FDG PET. Tc-99m MDP bone scintigraphy is more useful for localizing other sites and measuring activity than F-18 FDG PET.
Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.
Authors: P Dorian, M Wang, I David, C Feindel
Journal: Circulation (1991)

The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
THE RELATION OF THE BLOOD-VESSEL WALL TO COAGULATION OF THE BLOOD
Authors: BERTRAM M. BERNHEIM
Journal: JAMA (1910)

It has been shown by numerous observers, especially Wooldridge 1 and Morawitz, 2 that tissue extracts, such as those obtained from grinding up liver, kidney, muscle, etc., with salt solution, have a marked accelerating action on the coagulation of blood. Artus 3 has demonstrated that if salt solution was simply allowed to run over the surface of tissue which has been rendered as free as possible from blood the salt solution acquired an accelerating action. And if the solution of salt were run over the surface more than once, the accelerating properties of the salt solution increased in proportion.  This substance, or perhaps it would be better to say, these substances, although they have never been identified, have been given the name thrombokinase or zymoplastic substances.  And it was these to which Sahli 4 referred to in 1905 when, after a most careful study of hemophilia in all its aspects
Abstract 2356: The role of the Rac GTPases in PC-3 prostate cancer cell diapadesis
Authors: Surabhi Pathak, Moumita Chatterjee, Cara W. Dubyk, Linda Sequeira, Kenneth van Golen
Journal: Cancer Research (2010)

Abstract The Rho GTPases are molecular switches intimately involved in cancer metastasis through orchestrating changes in the cytoskeleton leading to motility and invasion. Previously, we demonstrated that RhoC GTPase was sufficient and required for PC-3 prostate cancer invasion. Furthermore, we demonstrated that targeted down-regulation of RhoC using either a dominant-negative RhoC or by specific shRNAs led to increased and sustained activation of Rac1 GTPase. Increased levels of active Rac1 led to morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition (EMT). Additionally, we demonstrated a requirement for active Rac1 GTPase in PC-3 tumor cell diapedesis across a bone marrow endothelial cell (BMEC) layer, an important step in prostate cancer skeletal metastasis. In the current study, we analyze the specific roles of Rac1, Rac3 and RhoG GTPases in tumor cell diapadesis. Use of specific siRNAs to down-regulate the individual Rac proteins demonstrated unique roles for each in promoting cell adhesion and diapedesis. We found Rac1 to be expressed at significantly higher levels than Rac3 or RhoG. However, RhoG appears to regulate PC-3 diapadesis at levels similar to Rac1. In contrast, Rac3 does not regulate diapadesis but controls PC-3 binding to substrates and BMECs. Together, these data suggest a role for coordinated activity of the Rac GTPases during diapadesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2356.
Violence in the Hospital
Authors: Jacquelyn Slomka
Journal: JAMA (1992)

<h3>To the Editor.</h3> —As a health care professional with more than 20 years' experience in four major American medical centers, I offer the following reflections on violence and health care. American society, perhaps more than any other society in the world, is characterized by its violence. A cultural propensity toward violence pervades all societal institutions, including medicine and health care. Although regrettable, it is therefore not unusual that health care professionals often find themselves witness to, victims of, and perhaps unquestioning participants in violence in the hospital setting. That medical care in itself can be extremely violent is often a shocking revelation for clinical newcomers as they watch patients sustain multiple violations of their bodies, the most brutal of which is perhaps cardiopulmonary resuscitation.<sup>1</sup> Another kind of violence in the hospital setting is interpersonal. Verbal and physical abuse toward medical students, residents, nurses, and other health care workers probably
Intracellular trafficking of factor VIII to von Willebrand factor storage granules.
Authors: J B Rosenberg, P A Foster, R J Kaufman, E A Vokac, M Moussalli, P A Kroner, R R Montgomery
Journal: Journal of Clinical Investigation (1998)

In plasma, von Willebrand factor (vWf) associates with Factor VIII (FVIII); however, the site at which these proteins first interact has not been defined. Administration of 1-desamino-8-D-arginine vasopressin (DDAVP) causes a rapid, concomitant elevation in plasma levels of both vWf and FVIII, suggesting the existence of a DDAVP-releasable storage pool for both proteins. To determine whether vWf and FVIII can associate intracellularly and colocalize to storage vesicles, we transfected AtT-20 cells with vWf and FVIII expression plasmids. FVIII alone was not detectable within storage granules; however, transfection of vWf cDNA into the same cell caused FVIII to alter its intracellular trafficking and to undergo granular storage, colocalizing to the vWf-containing granules. In contrast, colocalization of FVIII was not observed when these cells were transfected with plasmids encoding defective FVIII-binding vWf mutants. Transfection of bovine endothelial cells with FVIII further demonstrated vesicular storage of FVIII with vWf in Weibel-Palade bodies. Since gene therapy of hemophilia A may ultimately target endothelium or hematopoietic stem cells, the interaction between vWf and FVIII within a secretory cell is important. Thus, vWf can alter the intracellular trafficking of FVIII from a constitutive to a regulated secretory pathway, thereby producing an intracellular storage pool of both proteins.
Measurement of regional myocardial blood flow in dogs using a catheter semiconductor radiation detector
Authors: Y. SASAKI, B. PITT
Journal: Cardiovascular Research (1976)

Journal Article Measurement of regional myocardial blood flow in dogs using a catheter semiconductor radiation detector Get access YASUHITO SASAKI, YASUHITO SASAKI 2 From the Division of Nuclear Medicine and Cardiology, The Johns Hopkins University School of Medicine, Baltimore, USA 2Present address: The Third Department of Internal Medicine, St. Marianna University School of Medicine, 2095 Sugao, Takatsu-ku, Kawasaki, Japan 158. Search for other works by this author on: Oxford Academic PubMed Google Scholar BERTRAM PITT BERTRAM PITT From the Division of Nuclear Medicine and Cardiology, The Johns Hopkins University School of Medicine, Baltimore, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 10, Issue 4, July 1976, Pages 499–502, https://doi.org/10.1093/cvr/10.4.499 Published: 01 July 1976
Hyperglycemic Coma after Suprasellar Surgery
Authors: Gary R. Freidenberg, Edward J. Kosnik, Juan F. Sotos
Journal: New England Journal of Medicine (1980)

DISTURBANCES in water and electrolyte balance occur frequently after suprasellar surgery.1 Within a period of eight months we encountered three patients in whom life-threatening, nonketotic hyperglycemic coma occurred, in addition to electrolyte imbalances, after such an operation. A fourth patient with known diabetes insipidus had mild hyperglycemia after tonsillectomy. This hyperglycemic complication may be frequent, may occur more often in a less severe degree, and is probably preventable.Case ReportsThree children, five to 12 years of age, presented with histories of six to 12 months of progressive neurologic abnormalities. On admission to the hospital, all three were alert. The . . .
Women demand use of embryos without former partners' consent
Authors: C. Dyer
Journal: BMJ (2002)

Two women who hope to become pregnant through in vitro fertilisation treatment launched an unprecedented action at the High Court in London last week to try to save their frozen embryos from destruction.

The women, whose former partners asked for the embryos to be destroyed after their relationships ended, are challenging the law which says that both partners must consent to the use of an embryo.

Lawyers for Natallie Evans, aged 30, and Lorraine Hadley, aged 37, lodged papers at the High Court last week. Dame Elizabeth Butler-Sloss, president …
HEARING AIDS IN GENERAL PRACTICE
Authors: F. J. Cleminson
Journal: BMJ (1938)

If the physical intensity of a sound is increased ten times it is said to be increased by one bel (this name being in honour of Alexander Graham Bell, the inventor of the telephone).If the increase is a hundred times it is by two bels, and if a thousand times by three bels, and so on.For instance, the average noise in a very quiet room is two bels-that is, the noise is one hundred times as intense as that which would be just perceptible.A bel is divided into ten decibels, and
It Takes Four Years
Authors: Joseph M. Garfunkel
Journal: JAMA (1976)

THE COMMENTARY by Hejna 1 raises important questions for medical educators and particularly for those in schools that have regular or optional three-year curricula. Some of  issues raised, such as physician availability and maldistribution of medical care, are not educational in nature and require no discussion within this context. The concerns expressed regarding student stress, faculty fatigue, and  qualitative and quantitative aspects of curriculum content, however, merit further investigation and discussion. Since  last is  most significant issue, it will be addressed first.  The Three-Year Curriculum  We can all agree with Dr Hejna's conclusion that the body of fundamental biomedical science continues to increase, and...  physician must understand with considerable depth both morphology and its function. One can disagree, however, with  conclusion that it is therefore more difficult for  student to assimilate  expanding scientific material in a shortened period of time. The number of