tbuckley/cabot-search huggingface dataset:
Enhanced Expression of β3-Adrenoceptors in Cardiac Myocytes Attenuates Neurohormone-Induced Hypertrophic Remodeling Through Nitric Oxide Synthase
Authors: Catharina Belge, Joanna Hammond, Emilie Dubois-Deruy, Boris Manoury, Julien Hamelet, Christophe Beauloye, Andreas Markl, Anne-Catherine Pouleur, Luc Bertrand, Hrag Esfahani, Karima Jnaoui, Konrad R. Götz, Viacheslav O. Nikolaev, Annelies Vanderper, Paul Herijgers, Irina Lobysheva, Guido Iaccarino, Denise Hilfiker-Kleiner, Geneviève Tavernier, Dominique Langin, Chantal Dessy, Jean-Luc Balligand
Journal: Circulation (2013)

Background— β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown. Methods and Results— Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline. β3-AR colocalized with caveolin-3, endothelial nitric oxide synthase (NOS) and neuronal NOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in β3-TG mice, which also had less re-expression of fetal genes and transforming growth factor β1. Protection from Iso-induced hypertrophy was reversed by nonspecific NOS inhibition at low dose Iso, and by preferential neuronal NOS inhibition at high-dose Iso. Adenoviral overexpression of β3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine. Hypertrophy was restored on NOS or protein kinase G inhibition. Mechanistically, β3-AR overexpression inhibited phenylephrine-induced nuclear factor of activated T-cell activation. Conclusions— Cardiac-specific overexpression of β3-AR does not affect cardiac morphology at baseline but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.
Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline
Authors: J.-M. Dumonceau, M. Delhaye, A. Tringali, J. Dominguez-Munoz, J.-W. Poley, M. Arvanitaki, G. Costamagna, F. Costea, J. Devière, P. Eisendrath, S. Lakhtakia, N. Reddy, P. Fockens, T. Ponchon, M. Bruno
Journal: Endoscopy (2012)

<b>Background and aims: </b>Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis. <b>Methods:</b> Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline. <b>Summary of selected recommendations</b> For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 – 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D). For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A). For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A).
Engineering human cell-based, functionally integrated osteochondral grafts by biological bonding of engineered cartilage tissues to bony scaffolds
Authors: Celeste Scotti, Dieter Wirz, Francine Wolf, Dirk J. Schaefer, Vivienne Bürgin, Alma U. Daniels, Victor Valderrabano, Christian Candrian, Marcel Jakob, Ivan Martin, Andrea Barbero
Journal: Biomaterials (2009)
Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease
Authors: Elliott M. Antman
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes3 August 1999Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular DiseaseElliott M. Antman, MDElliott M. Antman, MDBrigham and Women's Hospital, Boston, Massachusetts. (Antman)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-3-199908030-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Lincoff AM, Topol EJ; eds. 368 pages. Totowa, NJ: Humana; 1999. $125.00. ISBN 0896037274. Order phone 973-256-1699.Field of medicine: Cardiology and internal medicine.Format: Hardcover book.Audience: Clinical cardiologists, vascular medicine specialists, general internists, and medical house officers.Purpose: To provide a comprehensive, definitive, and detailed overview of the preclinical and clinical development of glycoprotein IIb/IIIa receptor antagonists.Content: The text is divided into four sections that contain multiauthored chapters. The first section describes the basic pathophysiology of thrombosis in acute coronary syndromes; the processes of platelet activation, adhesion, and aggregation; and the development of antagonists to the glycoprotein ... Author, Article, and Disclosure InformationAffiliations: Brigham and Women's Hospital, Boston, Massachusetts. (Antman) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 August 1999Volume 131, Issue 3Page: 235-236KeywordsAcute myocardial infarctionClinical trialsGlycoproteinsPhase II clinical investigationPlatelet aggregationPlateletsRandomized trialsThrombosisUnstable anginaVascular medicine ePublished: 15 August 2000 Issue Published: 3 August 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Harmful impact of EU clinical trials directive:…and so has trial of melatonin in cancer related weight loss…
Authors: Max Watson
Journal: BMJ (2006)

EDITOR—The editorial by Hemminki and Kellokumpu-Lehtinen on the harmful impact of the EU Clinical Trials Directive highlights important issues that need to be addressed before investigator led cancer research becomes a thing of the past.1 The directive was supposed to protect patients by minimising biasing influences on clinical …
"The Music of Their Laughter
Authors: Marjorie C. Meehan
Journal: JAMA (1970)

Amidst the welter of discussion about the "generation gap," this book may be unique. Here are lengthy statements by 32 uppermiddle-class youngsters, presented without adult interpretation or valued judgment. The authors, themselves aged 32 and 21, interviewed 21 boys and 11 girls, all living in suburban areas in the Northeast. Evidently the subjects were chosen in part for their willingness to talk in the presence of a tape-recorder. The statements seem frank and uninhibited. Nearly all these high school and college students have used "soft" drugs, marijuana and hashish, several have used other drugs. Most of these students have had considerable sex experience, some of the girls have had abortions. The majority are still attending school, but express little enthusiasm for their studies. All are in comfortable financial circumstances, but several talk about stealing. A few are having psychotherapy. One of the subjects has been in the Marine Corps, one
THE MECHANISM OF THE FORMATION OF SARCOMA
Authors: ALEXIS CARREL
Journal: JAMA (1925)

In a previous article,<sup>1</sup>a description was given of the process by which blood macrophages inoculated in vitro with filtered extract of Rous sarcoma become transformed into malignant cells. The comparison of the normal and malignant strains showed that the sarcomatous monocyte is a diseased cell which is short lived, digests fibrin rapidly, transforms itself readily into fibroblasts, and reproduces the Rous principle. During this process, the culture assumes the appearance of a geographic map or moth-eaten cloth. It reminds one of the clear areas that Twort observed developing in his cultures of micrococcus after he had inoculated them with the lytic principle, called later bacteriophage by d'Herelle. In those areas, the micrococci underwent lysis and regenerated the lytic principle, and the phenomenon could repeat itself indefinitely. In an analogous manner, the macrophages inoculated with filtered sarcoma reproduce the Rous substance and die. The malignant element of the tumor is
An Address on the Teaching of Anatomy
Authors: C. B. Lockwood
Journal: BMJ (1888)

than permit recourse to the ligature.For such, digital compres- sion will always have great attractions.This case also suggests whether the older practice of manipulation of the aneurysm with a view to dislodgment of clots might not more frequently be resorted to, at all events in those cases where the disease is situated in the lower half of the body or at the shoulder.
Medical School Admissions-Reply
Authors: Frederick J. Ramsay
Journal: JAMA (1977)

Dr Smith describes accurately the frustrations experienced by those who play a role in the admissions process in medical schools. He also points out that the heavy reliance on numbers as represented by grade point averages (GPAs) and Medical College Admissions Test (MCAT) scores leaves little room for assessing other equally important factors such as motivation. All of us who daily confront the realities of medical school admissions, both in the process of selecting students and those ultimately selected, the matriculants, can share with him the sense of hopelessness he feels. However, I am not as confident about the prospects he sees with the solution he suggests. I believe the idea of a preadmissions work experience has merit in the theoretical sense but not, I fear, in the practical. Processing the applications of thousands of would-be students is very nearly overwhelming now. How could we possibly handle the
A Randomized Trial of Recombinant Staphylokinase Versus Alteplase for Coronary Artery Patency in Acute Myocardial Infarction
Authors: Steven Vanderschueren, Laurentino Barrios, Pitsanu Kerdsinchai, Paul Van den Heuvel, Luc Hermans, Mathias Vrolix, Filip De Man, Edouard Benit, Luc Muyldermans, Désiré Collen, Frans Van de Werf
Journal: Circulation (1995)

Background Recombinant staphylokinase (STAR) was shown recently to offer promise for coronary arterial thrombolysis in patients with evolving myocardial infarction. The present multicenter randomized open trial was designed to assess the thrombolytic efficacy, safety, and fibrin specificity of STAR relative to accelerated alteplase (recombinant tissue-type plasminogen activator [RTPA]). Methods and Results One hundred patients with evolving myocardial infarction of &lt;6 hours’ duration and with ST-segment elevation were allocated to accelerated and weight-adjusted RTPA over 90 minutes (52 patients) or to STAR (the first 25 patients to 10 mg and the next 23 patients to 20 mg given intravenously over 30 minutes). All patients received aspirin and intravenous heparin. The main end points were coronary artery patency and plasma fibrinogen levels at 90 minutes. Thrombolysis in Myocardial Infarction (TIMI) perfusion grade 3 at 90 minutes was achieved in 62% of STAR patients versus 58% of RTPA patients (risk ratio, 1.1; 95% CI, 0.76 to 1.5). With 10 mg STAR, TIMI grade 3 patency was 50% (risk ratio, 0.86; 95% CI, 0.54 to 1.4 versus RTPA); with 20 mg STAR, it was 74% (risk ratio, 1.3; 95% CI, 0.90 to 1.8 versus RTPA). Residual fibrinogen levels at 90 minutes were 118±47% (mean±SD) of baseline with STAR and 68±42% with RTPA ( P &lt;.0005). STAR therapy was not associated with an excess mortality or electric, hemorrhagic, mechanical, or allergic complications. However, patients developed antibody-mediated STAR-neutralizing activity from the second week after STAR treatment. As an addendum to the randomized study, 5 patients were given 40 mg STAR over 30 minutes, resulting in TIMI perfusion grade 3 at 90 minutes in 4 patients without fibrinogen breakdown (residual levels at 90 minutes of 105±8% of baseline). Conclusions STAR appears to be at least as effective for early coronary recanalization as and significantly more fibrin-specific than accelerated RTPA in patients with evolving myocardial infarction.
Association between Hepatitis B Virus and Essential Mixed Cryoglobulinemia
Authors: Y. Levo, P. D. Gorevic, H. J. Kassab, D. Zucker-Franklin, E. C. Franklin
Journal: New England Journal of Medicine (1977)

In view of a high frequency of liver involvement in patients with essential mixed cryoglobulinemia, we looked for evidence for hepatitis B virus infection in 25 serum specimens and 19 cryoprecipitates obtained from 30 patients. Three of the 25 serum specimens contained HBs Ag, and 12 had antibody. The frequency of positive results was increased to six and 11 of 19 respectively when cryoprecipitates were examined, and 14 of 19 (74 per cent) of the cryoprecipitates were positive for either HBs Ag or its antibody. Electron microscopy of four cryoprecipitates showed structures resembling the 20-nm and 27-nm spheres, tubules, as well as the Dane particles characteristic of hepatitis B virus infection. Since such infection appears to be involved in the pathogenesis of the syndrome, the term "essential mixed cryoglobulinemia" should be replaced by "mixed cryoglobulinemia secondary to hepatitis B virus" or perhaps to other viral infections. (N Engl J Med 296:1501–1504, 1977)
Impact of the Metabolic Syndrome on Macrovascular and Microvascular Outcomes in Type 2 Diabetes Mellitus
Authors: Carole A. Cull, Christine C. Jensen, Ravi Retnakaran, Rury R. Holman
Journal: Circulation (2007)

Background— The metabolic syndrome (MetS) and type 2 diabetes mellitus are both associated with increased cardiovascular disease risk. We examined retrospectively the degree to which the presence of MetS in individuals with type 2 diabetes mellitus increased their risk of diabetic complications using United Kingdom Prospective Diabetes Study data. Methods and Results— Of 5102 United Kingdom Prospective Diabetes Study patients recruited with newly diagnosed type 2 diabetes mellitus and followed up for a median of 10.3 years, 4542 had the requisite data for these analyses. After a 3-month dietary run-in, MetS, diagnosed with National Cholesterol Education Program Adult Treatment Panel III, World Health Organization, International Diabetes Federation, or European Group for the Study of Insulin Resistance criteria, was present in 61%, 38%, 54%, and 24%, respectively. Those with MetS by these criteria had increased cardiovascular disease risks relative to those without MetS of 1.33 (95% confidence interval 1.14 to 1.54), 1.45 (95% confidence interval 1.26 to 1.66), 1.23 (95% confidence interval 1.07 to 1.42), and 1.31 (95% confidence interval 1.10 to 1.57), respectively, but similar risks for microvascular complications. The positive predictive value of MetS for cardiovascular disease events, however, was only 18%, 13%, 18%, and 39%, respectively. Conclusions— MetS, diagnosed by Adult Treatment Panel III, World Health Organization, or International Diabetes Federation criteria, identifies diabetic patients at greater risk of macrovascular but not microvascular complications. Poor discrimination by MetS with respect to cardiovascular disease outcomes means that it is of limited clinical value for cardiovascular disease risk stratification in type 2 diabetes mellitus.
Diagnosis of a Liver Abscess with Ga-67 and Radiocolloid Tomography
Authors: VIJAY K. SANGAR, ADRIANA GINI, ROGELIO T. FUENTES, RICHARD A. HOLMES
Journal: Clinical Nuclear Medicine (1989)

A 46 year-old white male with fever of unknown origin demonstrated a multiloculated hepatic cyst on abdominal CT. Persistent fever and leukocytosis prompted Tc-99m Sulfur colloid liver-spleen and gallium-67 citrate imaging to identify a possible liver abscess. SPECT imaging provided pertinent clinical information that allowed the diagnosis of abscess to be made.
Soft-Tissue Tracheal Mass Associated With Previously Resected Bronchogenic Carcinoma
Authors: Lee B. Milner
Journal: JAMA (1981)

<h3>History</h3> A 64-year-old man with a known history of squamous cell carcinoma of the lung was admitted for increasing shortness of breath. In August 1975, a chest film showed a right lower lobe mass, which led to resection of a squamous cell carcinoma. In October 1978, he had recurrence of the carcinoma in the same general area, which was resected in November 1978. In June 1979, gradual onset of shortness of breath developed, which increased in the three weeks before admission on Sept 4, 1979. An admission chest film demonstrated increased prominence of the right hilum, which subsequently was evaluated with tomography. The tomograms demonstrated recurrent tumor in the right hilar and subcarinal areas. Within the midtrachea itself along the right lateral wall, a 2-cm well-defined soft-tissue density was demonstrated (Figure, arrowheads) (not apparent on plain films). Because of the tracheal mass, the patient underwent straight-tube bronchoscopy. No intratracheal lesion
Results of surgical repair of atrial septal defects in the middle-aged and elderly
Authors: D. E. Richmond, J. B. Lowe, B. G. Barratt-Boyes
Journal: Thorax (1969)

Twenty-six patients aged 45 or over at the time of surgical repair of a secundum atrial septal defect have been reviewed with the object of assessing the value of the operation. Pre-operatively 12 were classed as grade IIIA or worse on the basis of their symptoms. There were six deaths in the series, three early and three late. The remaining 20 patients were improved as judged by symptoms, physical examination, and radiographic and electrocardiographic criteria. In 11 patients catheterized pre- and post-operatively, it was found that the pulmonary arterial pressure had fallen following the repair, reaching normal levels in nine. It is concluded that surgical repair of secundum atrial septal defects is of material benefit to patients of this age-group.
Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non–Small-Cell Lung Cancer
Authors: Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2005)

Remarkable developments in the systemic treatment of advanced non–small-cell lung cancer have taken place in the past few years. Targeted therapies have been largely employed in patients with far advanced disease, and some of them have demonstrated consistent activity in this setting. Epidermal growth factor receptor (EGFR) inhibitors cause dramatic response in approximately 10% of white patients who had received prior chemotherapy. Responses are higher in Asians. These findings are at least partly caused by the substantially higher incidence of EGFR mutations in Asians compared with whites. Studies of EGFR inhibitors in combination chemotherapy in front-line therapy of advanced non–small-cell lung cancer have, however, failed to improve survival, and better understanding of interactions between chemotherapeutic agents and EGFR inhibitors will be essential in the development of more effective strategies.
THALLIUM SCINTIGRAPHY IN PEDIATRIC ONCOLOGY
Authors: Doina E. Tanasescu, Alan D. Waxman, Gerald Rosen, Lalitha Ramanna, Carole Hurvitz
Journal: Clinical Nuclear Medicine (1989)

Tanasescu, Doina E.; Waxman, Alan D.; Rosen, Gerald; Ramanna, Lalitha; Hurvitz, CaroleAuthor Information
Effect of a Pharmaceutical Care Program on Vascular Risk Factors in Type 2 Diabetes
Authors: Rhonda M. Clifford, Wendy A. Davis, Kevin T. Batty, Timothy M.E. Davis
Journal: Diabetes Care (2005)

OBJECTIVE—To examine the effect of a 12-month pharmaceutical care (PC) program on vascular risk in type 2 diabetes. RESEARCH DESIGN AND METHODS—We recruited 198 community-based patients randomized to PC or usual care. PC patients had face-to-face goal-directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessments and provision of other educational material. Clinical, biochemical, and medication-related data were sent regularly to each patient’s physician(s). The main outcome measure was change in HbA1c. A diabetes-specific risk engine was used to estimate changes in 10-year coronary heart disease (CHD) and stroke risk in patients without a history of cardiovascular disease. RESULTS—At total of 180 patients (91%) completed the study. Mean (95% CI) reductions were greater in PC case subjects (n = 92) than control subjects (n = 88) for HbA1c (−0.5% [95% CI −0.7 to −0.3] vs. 0 [−0.2 to 0.2]) and systolic (−14 mmHg [−19 to −9] vs. −7 [−11 to −2]) and diastolic (−5 mmHg [−8 to −3] vs. −2 [−4 to 1]) blood pressure (P ≤ 0.043). The improvement in HbA1c persisted after adjustment for baseline value and demographic and treatment-specific variables. The median (interquartile range) 10-year estimated risk of a first CHD event decreased in the PC case subjects (25.1% [15.6–36.2] to 20.3 [14.6–30.2]; n = 42, P = 0.002) but not in the control subjects (26.1% [17.2–39.4] vs. 26.4 [16.7–38.0]; n = 52, P = 0.17). CONCLUSIONS—A 12-month PC program in type 2 diabetes reduced glycemia and blood pressure. Pharmacist involvement contributed to improvement in HbA1c independently of pharmacotherapeutic changes. PC could prove a valuable component of community-based multidisciplinary diabetes care.