tbuckley/cabot-search huggingface dataset:
Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis
Authors: Abderrahim Nemmar, Peter H.M. Hoet, David Dinsdale, Jozef Vermylen, Marc F. Hoylaerts, Benoit Nemery
Journal: Circulation (2003)

Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking.Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied. Doses of 5 to 500 micro g of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release. The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 micro g of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100). The direct addition of as little as 0.5 micro g/mL DEPs to untreated hamster blood significantly shortened closure time in vitro.The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets. The kinetics of platelet activation are consistent with the reported clinical occurrence of thrombotic complications after exposure to pollutants. Our findings, therefore, provide a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.
1118. A Skin Gene Therapy Approach to Treat Hypertension Using Long-Term Expression and Systemic Delivery of Atrial Natriuretic Peptide (ANP) from the Skin
Authors: Jean-Philippe Therrien, Christine L. Tock, Manabu Ohyama, Jonathan C. Vogel
Journal: Molecular Therapy (2005)

In order to deliver therapeutic molecules systemically to treat cancers, skin diseases or systemic diseases, skin is a very attractive organ for gene therapy targeting. Because skin is renewable tissue, the ability to achieve long-term stable expression of a therapeutic gene requires targeting keratinocytes stem cells (KSC). Since unique specific extracellular markers to isolate living KSC do not exist, we have developed a system to select in vivo for the therapeutic gene using a bicistronic retroviral vector expressing the desired therapeutic gene and a selectable marker gene (MDR1) combined with topical colchicine treatment of the skin. Previous studies demonstrate in vivo enrichment for human MDR1-expressing keratinocytes that have been grafted to immunocompromised mice and treated with topical colchicine. As a model to validate our system we have chosen ANP as a therapeutic gene to treat hypertension. ANP is 126 amino acids (aa) peptide hormone synthetized mainly in cardiomyocytes of the heart as an inactive precursor (pro-ANP). Pro-ANP is secreted and converted into an active ANP (28 aa) by corin receptor in response to volume expansion and pressure overload. In target tissues, active ANP induce a signal transduction pathway in a receptor-dependent manner to decrease blood pressure. Although studies have demonstrated that ANP infusion can decrease blood pressure in hypertensive patients and animal models, stable long-term expression of ANP from a targeted tissue such as skin will be required for clinical application. We have now constructed and produced a retroviral vector containing ANP and MDR1 genes with a viral titer 104-105 cfu/ml, similar to titers obtained in other studies using MDR1 in a bicistronic system. FACS analysis using an anti-MDR antibody, shows that up to 46.4% and 11.5% of transduced-fibroblasts (Fb) or keratinocytes (Kc), respectively, express MDR1. Using a more sensitive rhodamine exclusion assay, we also demonstrate higher percentage of transduced-Fb and Kc expressing a functional MDR1 in the plasma membrane. We anticipate that colchicine selection will increase the percentage of ANP-expressing keratinocytes and human skin has been engineered in vitro with genetically modified Fb and Kc. Using an immuno-radiometric assay specific for ANP these bioengineered rafts are able to secrete significant levels of ANP into the raft culture media. We are currently grafting the genetically modified human skin onto immunocompromised mice to determine if the human ANP can be detected systemically in the mice and is able to decrease their systemic blood pressure.
Clinical Problems: Hepatitis in Dialysis Units in the United Kingdom
Authors: S. Polakoff, Y. E. Cossart, H. E. Tillett
Journal: BMJ (1972)

A prospective study of hepatitis in 20 dialysis units in the United Kingdom showed that the number of units with outbreaks increased from one in 1968 to three in 1969 and the overall attack rate rose from 1.7 to 5.3% in patients and from 0.5 to 1.3% in staff.In July 1969 a pilot study of patients' sera showed that all of the outbreaks were associated with Australia (Au) antigen. Au antigen was not detected in the unaffected units or in one unit in which there were several patients with abnormal liver function.In January 1970 systematic prospective testing for Au antigen was begun. Au antigen was detected in single patients in five more of the 20 units. The transfer of the affected patients to isolation for dialysis seemed to prevent the spread of infection in the units. The incidence of hepatitis in 1970 was 5.6% in patients and 0.4% in staff.
Points from Letters: Treatment of Alcoholism
Authors: L. M. Shirlaw
Journal: BMJ (1975)

vogue in the future should Parliament as at present constituted beconme too unwieldy to function effectively.Moreover, the medical profession would be freer to set up and supervise what mtust surely come, and that is a body of aware persons to interview at regular intervals all persons in paid authority above a certain level of responsibility, in- cluding doctors, lawyers, M.P.s, teachers, etc., regairding their continuing suitability to hold such authority.Under the pro- fession's present subservience to politics this would be difficult to implement, if at all."What shall it profit a man if he shall gain the whole world and lose his own soul?"And as a profession we are in grave danger of doing just that.-I am, etc.,
A CONTRIBUTION TO URETERAL SURGERY WITH FOUR CASES, INCLUDING A NEW OPERATION FOR DOUBLE URETERO-VAGINAL FISTULA.
Authors: X. O. WERDER
Journal: JAMA (1902)

Injuries to the ureters are unquestionably among the most serious and distressing complications which the surgeon can encounter in the course of his pelvic and abdominal work. Whether it be in the course of an operation for malignant disease, in which the ureter has become involved in the neoplasm, or the result of an accident, such an injury always proves a great trial to the nerve and skill of the operator. Accidents of this character will, no doubt, occur in the life of every busy abdominal and pelvic surgeon, no matter how careful and experienced he may be, and it is therefore his duty to prepare himself to deal with them promptly and skilfully. The technic of ureteral surgery fortunately has been perfected to such a degree that it is no longer necessary to follow an injury of the ureter by such a formidable operation as the removal of the
Improving teenagers' knowledge of emergency contraception: cluster randomised controlled trial of a teacher led intervention
Authors: A. Graham
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the effectiveness of a teacher led intervention to improve teenagers9 knowledge about emergency contraception. <b>Design:</b> Cluster randomised controlled trial. <b>Setting:</b> 24 mixed sex, state secondary schools in Avon, south west England. <b>Participants:</b> 1974 boys and 1820 girls in year 10 (14-15 year olds). <b>Intervention:</b> Teachers gave a single lesson on emergency contraception to year 10 pupils. The teachers had previously received in-service training on giving the lesson. The pupils were actively involved during the lesson. <b>Main outcome measures:</b> Questionnaires distributed to pupils at baseline and six months after the intervention assessed their knowledge of the correct time limits for hormonal emergency contraception and for use of the intrauterine device as emergency contraception, the proportion of pupils who were not virgins, the proportion who had used emergency contraception, and the pupils9 intention to use emergency contraception in the future. <b>Results:</b> The proportion of pupils knowing the correct time limits for both types of emergency contraception was significantly higher in the intervention group than in the control group at six months9 follow up (hormonal contraception: proportion of boys 15.9% higher (95% confidence interval 6.5% to 25.3%), girls 20.4% (10.4% to 30.4%); intrauterine device used as emergency contraception: boys 4.2% (0.7% to 7.7%), girls 10.7% (0.4% to 21.0%). The number of pupils needed to be taught for one more pupil to know the correct time limits was six for boys and five for girls. The intervention and control groups did not differ in the proportion of pupils who were not virgins, in the proportion who had used emergency contraception, and in the proportion intending to use emergency contraception in the future. <b>Conclusions:</b> The intervention significantly improved the proportion of boys and girls knowing the correct time limits for both types of emergency contraception. The intervention did not change the pupils9 sexual activity or use of emergency contraception. <h3>What is already known on this topic</h3> Use of condoms as a sole method of contraception is increasing Emergency contraception—either hormonal or the intrauterine device used as emergency contraception—can be used when condoms or other methods fail or are not used Awareness of emergency contraception in school pupils is high, but knowledge of specific details, such as the time period within which it can be used, is poor <h3>What this study adds</h3> A single lesson on emergency contraception given by teachers who had previously been trained improves the proportion of pupils aware of the correct time limits for use of both types of emergency contraception Such a lesson does not increase sexual activity or use of emergency contraception
The New Medical Marketplace: A Physician's Guide to the Health Care Revolution
Authors: James W. Allen
Journal: JAMA (1988)

User's guides accompany our purchases of cameras, appliances, autos, and other technical items. Reading the guides unlocks the potential of these unfamiliar purchases so that we may become proficient in their use.<i>The New Medical Marketplace</i>is a physician's guide to the current medical marketplace. Like any good user's guide, this book starts with historical background, then presents the theory of medical costs, and finally offers guidance to those who work in the medical marketplace. Immediately following the title page is a bar graph of medical costs expressed in terms of percentage of the gross national product (GNP) and average cost per hospital day. All the bars increase dramatically over the last two decades. This graph presents as clear a picture of the new medical marketplace as an exploded view of a product contained within a commercial user's guide. In the historical review the authors discuss how social changes have
Oxyphenbutazone in Pancreatitis
Authors: Benjamin B. Weisiger
Journal: JAMA (1966)

Oxyphenbutazone is a metabolic derivative of phenylbutazone. Experimental work showed this drug to possess an anti-inflammatory action, particularly in arthritic diseases.<sup>1-4</sup>Paulino-Netto and Dreiling found that the drug protected dogs against excessive pancreatic damage in experimentally induced pancreatitis.<sup>5</sup>This finding led us to study the drug in an attempt to determine its possible therapeutic role in the treatment of acute pancreatitis in man. To date, no drugs have been found that directly control the inflammatory process in the pancreas, although other approaches, such as the use of trypsininhibitors, are being sought.<sup>6</sup> <h3>Materials and Methods.—</h3> A double-blind study was conducted with the two study drugs, one of which was a placebo and the other, oxyphenbutazone. The patients receiving the drugs were randomized. The drug was given in addition to routine measures for the treatment of pancreatitis. These measures were varied in a particular patient according to the severity of
Literature and Medicine: Contributions to Clinical Practice
Authors: Rita Charon, Joanne Trautmann Banks, Julia E. Connelly, Anne Hunsaker Hawkins, Kathryn Montgomery Hunter, Anne Hudson Jones, Martha Montello, Suzanne Poirer
Journal: Annals of Internal Medicine (1995)

Introduced to U.S. medical schools in 1972, the field of literature and medicine contributes methods and texts that help physicians develop skills in the human dimensions of medical practice. Five broad goals are met by including the study of literature in medical education: 1) Literary accounts of illness can teach physicians concrete and powerful lessons about the lives of sick people; 2) great works of fiction about medicine enable physicians to recognize the power and implications of what they do; 3) through the study of narrative, the physician can better understand patients' stories of sickness and his or her own personal stake in medical practice; 4) literary study contributes to physicians' expertise in narrative ethics; and 5) literary theory offers new perspectives on the work and the genres of medicine. Particular texts and methods have been found to be well suited to the fulfillment of each of these goals. Chosen from the traditional literary canon and from among the works of contemporary and culturally diverse writers, novels, short stories, poetry, and drama can convey both the concrete particularity and the metaphorical richness of the predicaments of sick people and the challenges and rewards offered to their physicians. In more than 20 years of teaching literature to medical students and physicians, practitioners of literature and medicine have clarified its conceptual frameworks and have identified the means by which its studies strengthen the human competencies of doctoring, which are a central feature of the art of medicine.
Surgical training, supervision, and service
Authors: C. Collins
Journal: BMJ (1999)

Papers p 702 

For too long the National Health Service has depended on trainees undertaking a significant proportion of unsupervised elective surgery and an even greater proportion of emergency surgery,1 a fact that was formally recognised in 1990 in the calculation of suitable workload figures for a general surgical team in a district hospital.2 The published evidence to support the extent of trainees‘ involvement in specific areas of surgical service is, however, sparse, although periodically it has caused concern.3 4 In this week's issue Aitken et al provide further evidence that a high proportion of colorectal surgery is still being done by trainees. This practice is unsustainable, and doctors and managers must organise to enable more work to done by consultants.

Aitken et al present an audit of colorectal surgery performed in 1990–4 in three parts of the United Kingdom—comprising about a fifth of the population. This shows that consultants supervised only a fifth of the resections performed by trainees and were present at less than two thirds of the total number of operations (p 5 Supervision was even lower in emergency cases, particularly …
Multiple pathways of T-T interaction in the generation of cytotoxic T lymphocytes to alloantigens.
Authors: R B Corley, K A Switzer, D E Hudson, M A Cooley
Journal: The Journal of Experimental Medicine (1980)

The interaction of T helper (Th) cells with syngeneic and allogeneic cytotoxic T lymphocyte precursors (CTL.P) has been investigated. Unprimed and mixed lymphocyte culture-primed peripheral T cells were used as a source of Th. Thymocytes, which depend upon exogenous Th cells for activation, were used as a source of cytotoxic precursors. Data is presented that demonstrates that at least two pathways of T-T interaction can lead to the activation of cytotoxic lymphocytes. The first is an allogeneic effect, in which Th cells recognize and respond to alloantigens expressed on CTL.P. The second is the interaction of Th cells with syngeneic CTL.P, in which both cell types are thought to respond to alloantigens on stimulator cells. The latter interaction can be shown to be restricted by H-2-linked determinants when primed Th cells are used and allogeneic effects against thymocytes are minimized. Restricted interactions between unprimed Th cells and thymocyte CTL.P have never been observed. Mechanisms that may explain the difference between the interaction of unprimed and primed Th cells with CTL.P are discussed.
Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
Authors: Themistocles L. Assimes, Hilma Hólm, Sekar Kathiresan, Muredach P. Reilly, Gudmar Thorleifsson, Benjamin F. Voight, Jeanette Erdmann, Christina Willenborg, Dhananjay Vaidya, Changchun Xie, Chris C. Patterson, Thomas M. Morgan, Mary Susan Burnett, Mingyao Li, Mark A. Hlatky, Joshua W. Knowles, John R. Thompson, Devin Absher, Carlos Iribarren, Alan Go, Stephen P. Fortmann, Stephen Sidney, Neil Risch, Hua Tang, Richard M. Myers, Klaus Berger, Monika Stoll, Svati H. Shah, Gudmundur Thorgeirsson, Karl Andersen, Aki S. Havulinna, J. Enrique Herrera, Nauder Faraday, Yoonhee Kim, Brian G. Kral, Rasika A. Mathias, Ingo Ruczinski, Bhoom Suktitipat, Alexander F. Wilson, Lisa R. Yanek, Lewis C. Becker, Patrick Linsel-Nitschke, Wolfgang Lieb, Inke R. König, Christian Hengstenberg, Marcus Fischer, Klaus Stark, Wibke Reinhard, Janina Winogradow, Martina Grassl, Anika Grosshennig, Michael Preuss, Stefan Schreiber, H.-Erich Wichmann, Christa Meisinger, Jean Yee, Yechiel Friedlander, Ron Do, James B. Meigs, Gordon Williams, David M. Nathan, Calum A. MacRae, Liming Qu, Robert L. Wilensky, William H. Matthai, Atif N. Qasim, Hakon Hakonarson, Augusto D. Pichard, Kenneth M. Kent, Lowell Satler, Joseph M. Lindsay, Ron Waksman, Christopher W. Knouff, Dawn M. Waterworth, Max C. Walker, Vincent E. Mooser, Jaume Marrugat, Gavin Lucas, Isaac Subirana, Joan Sala, Rafael Ramos, Nicola Martinelli, Oliviero Olivieri, Elisabetta Trabetti, Giovanni Malerba, Pier Franco Pignatti, Candace Guiducci, Daniel Mirel, Melissa Parkin, Joel N. Hirschhorn, Rosanna Asselta, Stefano Duga, Kiran Musunuru, Mark J. Daly, Shaun Purcell, Sandra Eifert, Peter S. Braund, Benjamin J. Wright, Anthony J. Balmforth, Stephen G. Ball, Willem H. Ouwehand, Panos Deloukas, Michael Scholz, Francois Cambien, Andreas Huge, Thomas Scheffold, Veikko Salomaa, Domenico Girelli, Christopher B. Granger, Leena Peltonen, Pascal P. McKeown, David Altshuler, Olle Melander, Joseph M. Devaney, Stephen E. Epstein, Daniel J. Rader, Roberto Elosua, James C. Engert, Sonia S. Anand, Alistair S. Hall, Andreas Ziegler, Christopher J. O'Donnell, John A. Spertus, David Siscovick, Stephen M. Schwartz, Diane Becker, Unnur Thorsteinsdottir, Kari Stefansson, Heribert Schunkert, Nilesh J. Samani, Thomas Quertermous
Journal: Journal of the American College of Cardiology (2010)
England launches campaign on teenage pregnancies
Authors: A. Ferriman
Journal: BMJ (1999)

A £60m ($96m) campaign to halve the rate of teenage pregnancy in England over the next 10 yearswas launched by the government this week, after a year long investigation into the problem by the prime minister's Social Exclusion Unit.

Teenage boys will be targeted in the campaign with the message that they will be expected to support any children whom they father. They will be warned that the Child Support Agency will be able to pursue them for …
Abstract PR3: Myofibroblasts activated upon tissue injury and hypoxia promote development of castration-resistant prostate cancer.
Authors: Massimo Ammirante, Youngjin Kang, Michael Karin
Journal: Cancer Research (2013)

Abstract Background: Prostate cancer (PCa) progresses from prostatic intraepithelial neoplasia through locally invasive adenocarcinoma to castration resistant (CR) metastatic carcinoma. Although radical prostatectomy, radiation and androgen ablation are effective therapies for androgen-dependent (AD) PCa, metastatic CR-PCa is a major complication with high mortality. Cancer associated fibroblasts (CAFs) are a heterogeneous cell population of the tumor microenvironment that play important enabling roles in cancer development and progression. The mechanism resonsible for myofibroblast activation within the tumor microenvironment are not entirely clear and can be cancer-specific and heterogeneous. Methods: We used the Myc-CaP translpantable model of AD-PCa and the spontaneous mouse PCa model, TRAMP and we examinated how androgen ablation leads to induction of CXCL13 expression, which is critical for recruitment of B cells into tumor remnants and accellerate evolution of CR-PCa. We confirmed our data using human specimens of PCa. Results: Following castration, many myofibroblasts were present within the tumors remnants, which expressed CXCL13. Ablation of myofibroblasts led to a marked reduction in the infiltration of T, B and dendritic cells into the tumor remnants after the castration, reduced the expression of several chemokines, including CXCL13 and also delayed the re-growth of CR-PCa. We also found that androgen ablation led to increased expression of TGF-β in the tumor remnants. Inhibition of TGF-β signaling prevented activation of myofibroblasts, infiltration of B cells, induction of CXCL13 expressing myofibroblasts and also delayed the re-growth of CR-PCa. The main source of TGF-β in PCa tumors after castration appeared to be the fibroblast fraction. After castration, hypoxic areas appeared along with nuclear translocation of HIF-1α. Exposure of inactivated fibroblasts isolated from PCa tumors of non-castrated mice under hypoxic condition induced the expression of CTGF and TGF-β, which was HIF-1α dependent, and converted the fibroblasts into myofibroblasts. Conclusions: Our data show for the first time that androgen ablation led to hypoxia-induced myofibroblast activation, which is the cell type in the tumor stroma that recruits tumor-infiltrating B cells that allow the re-growth of CR-PCa through the production of lymphotoxin and IKKα nuclear translocation in the prostate epithelial cells. This abstract is also presented as Poster A75. Citation Format: Massimo Ammirante, Youngjin Kang, Michael Karin. Myofibroblasts activated upon tissue injury and hypoxia promote development of castration-resistant prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr PR3.
Elevated Prostaglandin D2 (PGD2) Levels in Bronchoalveolar Lavage Fluid (BALF) in Severe Asthma
Authors: M.L. Fajt, S. Balzar, J.B. Trudeau, J.Y. Westcott, S.E. Wenzel
Journal: Journal of Allergy and Clinical Immunology (2010)
Uterine Leiomyomata Discrepancy Between Scintigraphic and Radiographic Images
Authors: CHRISTOPHER J. PALESTRO, ROBERT W. SOLOMON, CHUN K. KIM, ALFRED J. SWYER, STANLEY J. GOLDSMITH
Journal: Clinical Nuclear Medicine (1990)

Extraosseous accumulation of the Tc-99m labeled bone imaging agents occurs in a variety of conditions, including metabolic, traumatic, vascular, and neoplastic (benign and malignant). Uptake of these agents in uterine leiomyomata with radiographic evidence of calcification has been described. This tumor was identified on bone scintigraphy performed on a woman in whom standard pelvic radiographs were not diagnostic.