tbuckley/cabot-search huggingface dataset:
Growth Hormone plus Childhood Low-Dose Estrogen in Turner's Syndrome
Authors: Judith L. Ross, Charmian A. Quigley, Dachuang Cao, Penelope Feuillan, Karen Kowal, John J. Chipman, Gordon B. Cutler
Journal: New England Journal of Medicine (2011)

Short stature and ovarian failure are characteristic features of Turner's syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner's syndrome.
How Doctors Think
Authors: Alfredo Morabia
Journal: Annals of Internal Medicine (2008)

Medical Writings: Book Notes15 July 2008How Doctors ThinkAlfredo Morabia, MD, PhDAlfredo Morabia, MD, PhDFrom Queens College, City University of New York, Flushing, New York.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-2-200807150-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Groopman J. 320 pages. Boston: Houghton Mifflin; 2007. $26.00. ISBN 9780618610037. Order at www.houghtonmifflinbooks.com.Field of medicine: Clinical practice.Format: Hardcover book.Audience: Clinicians (current and former) and medical students.Purpose: To help medically untrained people better understand and relate to physicians.Content: The book dissects the way clinicians think and the potential biases that may affect their reflection. The rationale is that because physicians learn primarily through practice and trial and error, their reasoning is vulnerable to typical cognitive biases. A series of case histories, several of which are personal experiences of the author as a physician or as ... Author, Article, and Disclosure InformationAffiliations: From Queens College, City University of New York, Flushing, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 2008Volume 149, Issue 2Page: 148KeywordsCase seriesDatabasesDecision analysisEmotionsEvidence based medicineHIVMalnutritionPsychologyReasoningSoftware tools ePublished: 15 July 2008 Issue Published: 15 July 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models
Authors: Catherine A. Eberlein, Daniel Stetson, Aleksandra A. Markovets, Katherine J. Al-Kadhimi, Zhongwu Lai, Paul R. Fisher, Catherine B. Meador, Paula Spitzler, Eiki Ichihara, Sarah J. Ross, Miika J. Ahdesmaki, Ambar Ahmed, Laura E. Ratcliffe, Elizabeth L. Christey O'Brien, Claire H. Barnes, Henry Brown, Paul D. Smith, Jonathan R. Dry, Garry Beran, Kenneth S. Thress, Brian Dougherty, William Pao, Darren A.E. Cross
Journal: Cancer Research (2015)

Abstract Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition. Cancer Res; 75(12); 2489–500. ©2015 AACR.
Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus
Authors: Norifumi Iijima, Melissa M. Linehan, Melodie Zamora, Debbie Butkus, Robert Dunn, Marilyn R. Kehry, Terri M. Laufer, Akiko Iwasaki
Journal: The Journal of Experimental Medicine (2008)

Although the importance of cytotoxic T lymphocytes and neutralizing antibodies for antiviral defense is well known, the antiviral mechanism of Th1 remains unclear. We show that Th1 cells mediate noncytolytic antiviral protection independent of direct lysis through local secretion of IFN-γ after herpes simplex virus (HSV) 2 infection. IFN-γ acted on stromal cells, but not on hematopoietic cells, to prevent further viral replication and spread throughout the vaginal mucosa. Importantly, unlike other known Th1 defense mechanisms, this effector function did not require recognition of virally infected cells via MHC class II. Instead, recall Th1 response was elicited by MHC class II+ antigen-presenting cells at the site of infection. Dendritic cells (DCs) were not required and only partially sufficient to induce a recall response from memory Th1 cells. Importantly, DCs and B cells together contributed to restimulating memory CD4 T cells to secrete IFN-γ. In the absence of both DCs and B cells, immunized mice rapidly succumbed to HSV-2 infection and death. Thus, these results revealed a distinct mechanism by which memory Th1 cells mediate noncytolytic IFN-γ–dependent antiviral protection after recognition of processed viral antigens by local DCs and B cells.
Chromosome Analysis before Birth and its Value in Genetic Counselling
Authors: M. E. Ferguson-Smith, M. A. Ferguson-Smith, N. C. Nevin, M. Stone
Journal: BMJ (1971)

Chromosome analysis of amniotic cell cultures was achieved in 29 out of 30 consecutive patients who were referred for genetic counselling during pregnancy. Amniocentesis was performed without any apparent untoward maternal or fetal complication. The only pregnancy terminated was that of a carrier of X-linked granulomatous disease, in whom the amniotic cells showed that the fetus was male and also had Down's syndrome (trisomy G). Chromosome analysis in the remaining 28 patients showed normal karyotypes. The interval between amniocentesis and a definitive karyotype varied from 7 to 31 (average 18.4) days.The reliability of chromosome analysis from amniotic cell culture and of fetal sex determination by means of the sex chromatin and Y-fluorescence techniques was studied further in amniotic fluid from cases of therapeutic abortion and of rhesus incompatibility. The fetal sex was correctly determined in all cases. It is concluded that antenatal diagnosis of genetic disease by amniocentesis now permits a more practical approach to genetic counselling.
PRIMA-1MET induces nucleolar translocation of Epstein-Barr virus-encoded EBNA-5 protein
Authors: György Stuber, Emilie Flaberg, Gabor Petranyi, Rita Ötvös, Nina Rökaeus, Elena Kashuba, Klas G Wiman, George Klein, Laszlo Szekely
Journal: Molecular Cancer (2009)

The low molecular weight compound, PRIMA-1MET restores the transcriptional transactivation function of certain p53 mutants in tumor cells. We have previously shown that PRIMA-1MET induces nucleolar translocation of p53, PML, CBP and Hsp70. The Epstein-Barr virus encoded, latency associated antigen EBNA-5 (also known as EBNA-LP) is required for the efficient transformation of human B lymphocytes by EBV. EBNA-5 associates with p53-hMDM2-p14ARF complexes. EBNA-5 is a nuclear protein that translocates to the nucleolus upon heat shock or inhibition of proteasomes along with p53, hMDM2, Hsp70, PML and proteasome subunits. Here we show that PRIMA-1MET induces the nucleolar translocation of EBNA-5 in EBV transformed B lymphoblasts and in transfected tumor cells. The PRIMA-1MET induced translocation of EBNA-5 is not dependent on the presence of mutant p53. It also occurs in p53 null cells or in cells that express wild type p53. Both the native and the EGFP or DSRed conjugated EBNA-5 respond to PRIMA-1MET treatment in the same way. Image analysis of DSRed-EBNA-5 expressing cells, using confocal fluorescence time-lapse microscopy showed that the nucleolar translocation requires several hours to complete. FRAP (fluorescence recovery after photobleaching) and FLIP (fluorescence loss in photobleaching) measurements on live cells showed that the nucleolar translocation was accompanied by the formation of EBNA-5 aggregates. The process is reversible since the aggregates are dissolved upon removal of PRIMA-1MET. Our results suggest that mutant p53 is not the sole target of PRIMA-1MET. We propose that PRIMA-1MET may reversibly inhibit cellular chaperons that prevent the aggregation of misfolded proteins, and that EBNA-5 may serve as a surrogate drug target for elucidating the precise molecular action of PRIMA-1MET.
The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood
Authors: Kris N.J. Stevens, Olga Crespo-Biel, Edith E.M. van den Bosch, Aylvin A. Dias, Menno L.W. Knetsch, Yvette B.J. Aldenhoff, Frederik H. van der Veen, Jos G. Maessen, Ellen E. Stobberingh, Leo H. Koole
Journal: Biomaterials (2009)
To Congressmen and Senators.
Authors: C. H. Hughes
Journal: JAMA (1902)

St. Louis, April 19, 1902. <h3>My dear Sir:</h3> —You would, 1 am sure, please the medical profession of the country by favoring a broad representative bill for a National Board of Health, representing the whole profession, as well as the Army, Navy and Marine-Hospital Service, with its chief eligible to a place in the President's cabinet. The presidents of the Academy of Medicine and American Medical Association might be members, and one member might be nominated by the Senate and one by the House of Representatives for the people and states to make up the composition of the first board. One representative might come also from the American Association for the Advancement of Science. The present board scheme is too much and too exclusively Army, Navy and Marine. Very truly yours,
Interventional Radiology of the Abdomen
Authors: Harvey A. Koolpe
Journal: JAMA (1982)

<i>Interventional Radiology of the Abdomen</i>provides a practical "state-of-the-art" review of invasive radiological methods. One of the virtues of this textbook is the authors' repeated emphasis on the role of the interventional radiologist as a clinician involved in the continuous daily care of patients. Interspersed among numerous "pearls" both of technique and judgment, "participation" in patient care is echoed throughout the book. The equipment and specific protocols for each procedure are described thoroughly and reflect the experience and personal preference of the authors. In some instances they acknowledge alternative techniques, but they too often leave the reader with the impression that no other simpler or less expensive methodology exists. The most notable example of this is their recommendation to use the Meditech deflector handle and catheter system for biliary stone retrieval; the less costly Smith-Bean-Mahorner system, which I have found highly effective, is noted only in the references. Each of
The Pill: Facts and Fallacies About Today's Oral Contraceptives
Authors: John W. Huffman
Journal: JAMA (1969)

ABSTRACT No one denies that women who take birth-control pills may become seriously ill. The question is: Did the pills they took cause the disease attributed to them? If so, how likely are patients to have such iatrogenic disorders? Is a patient, after understanding its relative hazards, justified in taking the more convenient pill in preference to using some other, less-certain contraceptives?Robert Kistner answers questions like these for patients in a specific fashion. He has gathered together the conflicting data on the Pill and blood clots, the Pill and cancer, the Pill and diabetes and the relationship of the Pill and numerous other morbid states with which it is or is alleged to be associated. In each case, he relates the pertinent backup statistical studies, points out their significance (or lack of it), and draws judicial conclusions in language patients can understand.The Pill is more than a book about
Phase II Investigation of Pentostatin in Multiple Myeloma: A Southwest Oncology Group Study
Authors: Michael R. Grever, John Crowley, Sydney Salmon, Richard McGee, Eric H. Kraut, Saundra S. Buys, Saul E. Rivikin
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Phase II Investigation of Pentostatin in Multiple Myeloma: A Southwest Oncology Group Study Get access Michael R. Grever, Michael R. Grever Search for other works by this author on: Oxford Academic PubMed Google Scholar John Crowley, John Crowley Search for other works by this author on: Oxford Academic PubMed Google Scholar Sydney Salmon, Sydney Salmon Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard McGee, Richard McGee Search for other works by this author on: Oxford Academic PubMed Google Scholar Eric H. Kraut, Eric H. Kraut Search for other works by this author on: Oxford Academic PubMed Google Scholar Saundra S. Buys, Saundra S. Buys Search for other works by this author on: Oxford Academic PubMed Google Scholar Saul E. Rivikin Saul E. Rivikin Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 22, 21 November 1990, Pages 1778–1779, https://doi.org/10.1093/jnci/82.22.1778 Published: 21 November 1990 Article history Received: 01 March 1990 Revision received: 28 August 1990 Accepted: 06 September 1990 Published: 21 November 1990
Smartphone Mobile Application Delivering Personalized, Real-Time Sun Protection Advice
Authors: David B. Buller, Marianne Berwick, Kathy Lantz, Mary Klein Buller, James Shane, Ilima Kane, Xia Liu
Journal: JAMA Dermatology (2015)

Mobile smartphones are rapidly emerging as an effective means of communicating with many Americans. Using mobile applications (apps), they can access remote databases, track time and location, and integrate user input to provide tailored health information.A smartphone mobile app providing personalized, real-time sun protection advice was evaluated in a randomized clinical trial.The trial was conducted in 2012 and had a randomized pretest-posttest controlled design with a 10-week follow-up. Data were collected from a nationwide population-based survey panel. A sample of 604 non-Hispanic and Hispanic adults from the Knowledge Panel 18 years or older who owned an Android smartphone were enrolled.The mobile app provided advice on sun protection (ie, protection practices and risk of sunburn) and alerts (to apply or reapply sunscreen and get out of the sun), hourly UV Index, and vitamin D production based on the forecast UV Index, the phone's time and location, and user input.Percentage of days using sun protection and time spent outdoors (days and minutes) in the midday sun and number of sunburns in the past 3 months were collected.Individuals in the treatment group reported more shade use (mean days staying in the shade, 41.0% vs 33.7%; P = .03) but less sunscreen use (mean days, 28.6% vs 34.5%; P = .048) than controls. There was no significant difference in number of sunburns in the past 3 months (mean, 0.60 in the treatment group vs 0.62 for controls; P = .87). Those who used the mobile app reported spending less time in the sun (mean days keeping time in the sun to a minimum, 60.4% for app users vs 49.3% for nonusers; P = .04) and using all protection behaviors combined more (mean days, 39.4% vs 33.8%; P = .04).The mobile app improved some sun protection. Use of the mobile app was lower than expected but associated with increased sun protection. Providing personalized advice when and where people are in the sun may help reduce sun exposure.
THE EFFECT OF THE KIDNEY OF TEMPORARY COMPRESSION OF ITS VESSELS
Authors: D. N. EISENDRATH
Journal: JAMA (1910)

<h3>1. PURPOSE</h3> Considerable difference of opinion exists among surgeons in regard to the advisability of compressing the renal vessels to control hemorrhage during nephrotomy. Some maintain that in addition to the temporary functional disturbance,<sup>1,2</sup>which often follows such compression, the anemia so produced causes serious and permanent degenerative changes of the parenchyma. At a recent meeting of the Chicago Urological Society Dr. A. D. Bevan stated that it would be of considerable interest to observe experimentally what effect such temporary interruption of the blood-supply of the kidney has on its parenechyma. Our investigation was undertaken to observe how long the circulation through the renal vessels can be completely obstructed, without causing permanent degencrative changes in the kidney. This question is not only of interest to the pathologist, but is of even greater importance to those surgeons who believe in employing one of the various methods of compressing the renal
Respiratory Obstruction in Haemophilic Patients
Authors: R. A. L. Leatherdale
Journal: BMJ (1960)

<h3>Objective:</h3> To investigate income gradients in motor vehicle traffic injury hospitalisation for vehicle occupants and pedestrians/cyclists among children in urban and rural Canada. <h3>Design:</h3> Four years (2001/02–2004/05) of acute-care hospitalisation discharge records for children aged 0–19 years were analysed. International Classification of Disease codes were used to determine hospitalisations due to motor vehicle traffic incidents for occupants and pedestrians/cyclists. Rates of injury (per 10 000 person years) were calculated by neighbourhood income quintiles for urban and rural areas. <h3>Results:</h3> Among children (0–19 years), rates of vehicle occupant hospitalisation were higher in rural (5.07, 95% CI 4.90 to 5.25) than urban areas (2.08, 95% CI 2.03 to 2.14). In rural areas, children from lower income neighbourhoods had higher vehicle occupant hospitalisation rates than those from the richest neighbourhoods (5.52, 95% CI 5.13 to 5.93 vs 4.30, 95% CI 3.97 to 4.66). In urban areas vehicle occupant hospitalisation rates were similar among children from the poorest and richest neighbourhoods—but higher among children from middle income neighbourhoods. In urban areas, but not rural areas, the hospitalisation rate for pedestrians/cyclists systematically increased with decreasing neighbourhood income. In urban areas the pedestrian/cyclist hospitalisation rate was four times higher for children from the poorest (1.40, 95% CI 1.25 to 1.57) than from the richest (0.34, 95% CI 0.28 to 0.43) neighbourhoods. <h3>Conclusions:</h3> While vehicle occupant and pedestrian/cyclist motor vehicle traffic injuries are more frequent among children from lower income neighbourhoods, gradients are most pronounced for pedestrians/cyclists in urban areas.
S99 A Functional Variant of Elafin with Improved Anti-Inflammatory Activity
Authors: Dm Small, M Zani, D Quinn, S Weldon, Df McAuley, P McNally, T Moreau, Cc Taggart
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Elafin is a well-known serine protease inhibitor produced by epithelial and inflammatory cells with anti-inflammatory properties. Previous work has shown that unregulated protease activity can cause the proteolytic cleavage of elafin, therefore impairing the innate immune function of the protein. Consequently, the aim of this study was to generate a variant of elafin that would demonstrate increased protease resistance whilst retaining many of the beneficial characteristics of the parent molecule. <h3>Methods</h3> Two elafin variants (GG-elafin and QQ-elafin) were recombinantly synthesised in a yeast-based expression system and subsequently tested for antiprotease, transglutaminase and protease susceptibility. In addition, the LPS neutralisation activity of the GG-variant was evaluated in <i><i>in vitro</i></i> based assays and an <i><i>in vivo</i></i> mouse model of LPS-induced acute lung inflammation. <h3>Results</h3> GG- and QQ-elafin retained similar antiprotease and transglutaminase activity compared to wild-type elafin (WT-elafin). When incubated with diseased bronchoalveolar lavage fluid (BALF), the elafin variants displayed significantly enhanced resistance to degradation when compared to WT-elafin. Intriguingly, both variants, but particularly GG-elafin, demonstrated improved LPS neutralisation by inhibiting cytokine expression in monocytic cells. Moreover, the GG-elafin showed improved anti-inflammatory properties in a mouse model of LPS-induced acute lung inflammation with significantly decreased inflammatory cell counts, namely neutrophils (<i>p</i> = 0.0362). Furthermore, total BAL protein levels were significantly decreased (<i>p</i> = 0.0336) and a reduction in pro-inflammatory cytokine/chemokine levels was observed in mice treated with GG-elafin compared to those treated with WT-elafin. <h3>Conclusions</h3> <b></b>Site-specific mutants of elafin, particularly GG-elafin, showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases, particularly acute lung injury (ALI).
The Myelodysplastic Syndromes: Current Approaches to Therapy
Authors: Bruce D. Cheson
Journal: Annals of Internal Medicine (1990)

Purpose: To review the current therapeutic options for patients with the myelodysplastic syndromes. Data Identification: Studies reported between 1968 and September 1989 were identified through computer searches using MEDLINE and through extensive searching of bibliographies of identified articles. Study Selection: All articles, abstracts, and reviews were evaluated, and those that contained therapeutic data were analyzed for response rates, survival, and toxicity. Results of Data Synthesis: Therapies for the myelodysplastic syndromes have included hormones, chemotherapy, bone marrow transplantation, and differentiating agents, including hematopoietic growth factors. With the exception of bone marrow transplantation, none is curative or increases survival. Hematopoietic growth factors are of interest for clinical trials, because they increase the number of neutrophils and, occasionally, the number of platelets in patients with the myelodysplastic syndromes. Nonetheless, hematopoietic growth factors are not without toxicity; most notably, they are associated with a risk for acceleration to acute myeloid leukemia, and their effect on survival remains unknown. Conclusions: Standard therapy for the myelodysplastic syndromes is supportive care. When the disease progresses, patients with aggressive histologic or other poor-risk features should be considered for aggressive chemotherapy, with or without growth factors, or bone marrow transplantation. Patients with good prognostic features are candidates for therapy with growth factors or other potential differentiating agents. Carefully designed and conducted clinical trials that incorporate correlative laboratory science are essential to developing a more rational approach to therapy.