tbuckley/cabot-search huggingface dataset:
Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial
Authors: Jean-Michel Molina, Pedro Cahn, Beatriz Grinsztejn, Adriano Lazzarin, Anthony Mills, Michael Saag, Khuanchai Supparatpinyo, Sharon Walmsley, Herta Crauwels, Laurence T Rimsky, Simon Vanveggel, Katia Boven
Journal: The Lancet (2011)
ON HÆMORRHAGIC CYSTS OF THE THYROID GLAND
Authors: W. I. Bradley
Journal: The Journal of Experimental Medicine (1896)

1. All the features peculiar to the gross cysts of the thyroid gland which possess fluid contents appear to indicate that they are essentially of haemorrhagic origin. 2. While these gross cysts would seem more especially to occur in glands which already present the features of parenchymatous goitre, the theory of Wölfler that they originate as a consequence of spontaneous rupture of the vesicles is unsatisfactory. 3. It would seem more probable that these large cysts are due to rupture, traumatic or otherwise, of some of the vessels of the organ. The frequent signs of small haemorrhages in cases of parenchymatous goitre without evidence of associated gross change in the surrounding vesicles, the structure of the organ and its exposed position, all appear to favour this view.
Progression of early structural lung disease in young children with cystic fibrosis assessed using CT
Authors: Lauren S Mott, Judy Park, Conor P Murray, Catherine L Gangell, Nicholas H de Klerk, Philip J Robinson, Colin F Robertson, Sarath C Ranganathan, Peter D Sly, Stephen M Stick
Journal: Thorax (2011)

<h3>Background</h3> Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated. <h3>Aim</h3> To determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression. <h3>Methods</h3> 143 children aged 0.2–6.5 years with CF from a newborn screened population contributed 444 limited slice annual chest CT scans for analysis that were scored for bronchiectasis and air trapping and analysed as paired scans 1 year apart. Logistic and linear regression models, using generalised estimating equations to account for multiple measures, determined associations between persistence and progression over 1 year and age, sex, severe cystic fibrosis transmembrane regulator (CFTR) genotype, pancreatic sufficiency, current respiratory symptoms, and neutrophilic inflammation and infection measured by bronchoalveolar lavage. <h3>Results</h3> Once detected, bronchiectasis persisted in 98/133 paired scans (74%) and air trapping in 178/220 (81%). The extent of bronchiectasis increased in 139/227 (63%) of paired scans and air trapping in 121/264 (47%). Radiological progression of bronchiectasis and air trapping was associated with severe CFTR genotype, worsening neutrophilic inflammation and pulmonary infection. <h3>Discussion</h3> CT-detected structural lung disease identified in infants and young children with CF persists and progresses over 1 year in most cases, with deteriorating structural lung disease associated with worsening inflammation and pulmonary infection. Early intervention is required to prevent or arrest the progression of structural lung disease in young children with CF.
Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study
Authors: Sudeep S Gill, Paula A Rochon, Nathan Herrmann, Philip E Lee, Kathy Sykora, Nadia Gunraj, Sharon-Lise T Normand, Jerry H Gurwitz, Connie Marras, Walter P Wodchis, Muhammad Mamdani
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. <b>Design</b> Population based retrospective cohort study. <b>Setting</b> Ontario, Canada. <b>Patients</b> 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an atypical antipsychotic and 14 865 dispensed a typical antipsychotic). <b>Main outcome measures</b> Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient9s admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. <b>Results</b> After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. <b>Conclusion</b> Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.
Multitarget Stool DNA Testing for Colorectal-Cancer Screening
Authors: Thomas F. Imperiale, David F. Ransohoff, Steven H. Itzkowitz, Theodore R. Levin, Philip Lavin, Graham P. Lidgard, David A. Ahlquist, Barry M. Berger
Journal: New England Journal of Medicine (2014)

An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
The evolution of the coronary care unit
Authors: D Julian
Journal: Cardiovascular Research (2001)

We can now see that the development of the coronary care unit, which Braunwald [1] has called ‘the single most important advance in the treatment of AMI’, was inevitable. But this was not obvious to most cardiologists of the day because so few of them considered the management of myocardial infarction to be a primary concern. They saw the diagnosis and treatment of congenital and rheumatic heart disease to be their main function. In 1956, when I was training under Paul Wood at the National Heart Hospital, I was advised by a Professor of Medicine in London not to become a cardiologist because ‘all the mitrals had been operated on’.

Insofar as there was an interest in myocardial infarction, this was concentrated on two modes of treatment — anticoagulants and inotropic drugs. Irving Wright of New York wrote a 1000-page book on myocardial infarction, mentioning cardiac arrest and ventricular fibrillation in a footnote only [2]. The main concern of the book was the use of anticoagulant drugs. There was also a lively interest in the use of noradrenaline in shock; it was claimed that this drug reduced the mortality of this complication from 80 to 50%.

There were, however, other developments taking place in the 1950s that led to the explosion of interest in coronary disease that took place in the 1960s. Beck had pioneered open-chest defibrillation and reported the successful resuscitation of a physician with myocardial infarction in 1953 [3]. He wrote, with remarkable foresight, ‘This one experience indicates that resuscitation from a fatal heart attack is not impossible and might be applied to those who die in hospital and perhaps to those who die outside hospital’. A few more cases were described in the succeeding years and it became fashionable for the more enthusiastic surgeons to …
Alternate-day prednisone therapy and human lymphocyte subpopulations.
Authors: A S Fauci, D C Dale
Journal: Journal of Clinical Investigation (1975)

The mechanisms and kinetics of the immunosuppressive effects of alternate-day prednisone were investigated in a group of patients with a variety of inflammatory diseases receiving a range of alternate-day prednisone doses from 5 to 120 mg. Total circulating lymphocyte and monocyte counts, as well as proportions of lymphocyte subpopulations defined both by surface markers and by in vitro functional capacities, were studied. At 8 a. m. of the day on prednisone, just before drug administration, lymphocyte and monocyte counts, proportions of lymphocyte subpopulations, as well as in vitro lymphocyte blastogenic responses to various mitogenic and antigenic stimuli were normal. 4 h after the administration of prednisone, there was a profound lymphocytopenia and monocytopenia, with a differential depletion of thymus-derived lymphocytes as well as various functionally defined lymphocyte subpopulations. Lymphocyte kinetic studies using a radioactive chromium-labeled autologous lymphocytes showed that the lymphocytopenia was due predominantly to a transient depletion of the recirculating portion of the intravascular lymphocytepool. All these parameters returned to normal by 8 a.m. of the following day (off prednisone) and remained normal throughout the day. This very transient lymphocytopenia and monocytopenia after prednisone, with normal cell numbers, proportions, and functions throughout the remainder of the 2-day cycle, was associated with suppression of disease activity, yet did not affect cutaneous delayed hypersensitivity in these patients nor increase the likelihood of infectious complications. This drug-associated cyclic and transient monocytopenia and selective lymphocytopenia is best explained by a redistribution of recirculating lymphocytes to other body compartments, particularly the bone marrow.
Intervention at the Level of the Neuroendocrine–Immune Axis and Postoperative Pneumonia Rate in Long-term Alcoholics
Authors: Claudia Spies, Verena Eggers, Gyongyi Szabo, Alexandra Lau, Vera von Dossow, Helge Schoenfeld, Hilke Althoff, Katrin Hegenscheid, Birgit Bohm, Torsten Schroeder, Sebastian Pfeiffer, Sabine Ziemer, Christian Paschen, Martin Klein, Christian Marks, Peter Miller, Michael Sander, Klaus-D. Wernecke, Evelin Achterberg, Udo Kaisers, Hans-Dieter Volk
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus–pituitary–adrenal (HPA) axis and immunity.Objectives: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine–immune axis and development of postoperative pneumonia in long-term alcoholic patients.Methods: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 μg/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine–immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery.Measurements and Main Results: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients.Conclusions: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.
Intravenous Plus Oral Amiodarone, Atrial Septal Pacing, or Both Strategies to Prevent Post-Cardiothoracic Surgery Atrial Fibrillation: The Atrial Fibrillation Suppression Trial II (AFIST II)
Authors: C. Michael White, Michael F. Caron, James S. Kalus, Heidi Rose, Jessica Song, Prabashni Reddy, Robert Gallagher, Jeffrey Kluger
Journal: Circulation (2003)

Background— The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. Methods and Results— Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2×2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% ( P =0.037 and P =0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P =0.047 and P =0.040, respectively). Conclusions— Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.
Effect of Fish Oil on Ventricular Tachyarrhythmia and Death in Patients With Implantable Cardioverter Defibrillators
Authors: Ingeborg A. Brouwer, Peter L. Zock, A. John Camm, Dirk Böcker, Richard N. W. Hauer, Eric F. D. Wever, Carla Dullemeijer, Jacintha E. Ronden, Martijn B. Katan, Andrzej Lubinski, Helga Buschler, Evert G. Schouten, for the SOFA Study Group
Journal: JAMA (2006)

Very-long-chain n-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish are thought to reduce risk of sudden death, possibly by reducing susceptibility to cardiac arrhythmia.To study the effect of supplemental fish oil vs placebo on ventricular tachyarrhythmia or death.The Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) was a randomized, parallel, placebo-controlled, double-blind trial conducted at 26 cardiology clinics across Europe. A total of 546 patients with implantable cardioverter-defibrillators (ICDs) and prior documented malignant ventricular tachycardia (VT) or ventricular fibrillation (VF) were enrolled between October 2001 and August 2004. Patients were randomly assigned to receive 2 g/d of fish oil (n = 273) or placebo (n = 273) for a median period of 356 days (range, 14-379 days).Appropriate ICD intervention for VT or VF, or all-cause death.The primary end point occurred in 81 (30%) patients taking fish oil vs 90 (33%) patients taking placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.64-1.16; P = .33). In prespecified subgroup analyses, the HR was 0.91 (95% CI, 0.66-1.26) for fish oil vs placebo in the 411 patients who had experienced VT in the year before the study, and 0.76 (95% CI, 0.52-1.11) for 332 patients with prior myocardial infarctions.Our findings do not indicate evidence of a strong protective effect of intake of omega-3 PUFAs from fish oil against ventricular arrhythmia in patients with ICDs.clinicaltrials.gov Identifier: NCT00110838.
Quantitative and qualitative analysis of real-time myocardial contrast echocardiography in the detection of coronary artery stenosis
Authors: So-Joong Rim, Hyun-Joo Kim, Jeong-ah Ahn, Deok-Kyu Cho, Seok-Min Kang, Donghoon Choi, Yangsoo Jang, Seung-Yun Cho, Namsik Chung
Journal: Journal of the American College of Cardiology (2002)
Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling
Authors: Emilie Bourdonnay, Zbigniew Zasłona, Loka Raghu Kumar Penke, Jennifer M. Speth, Daniel J. Schneider, Sally Przybranowski, Joel A. Swanson, Peter Mancuso, Christine M. Freeman, Jeffrey L. Curtis, Marc Peters-Golden
Journal: The Journal of Experimental Medicine (2015)

JAK-STAT signaling mediates the actions of numerous cytokines and growth factors, and its endogenous brake is the family of SOCS proteins. Consistent with their intracellular roles, SOCS proteins have never been identified in the extracellular space. Here we report that alveolar macrophages can secrete SOCS1 and -3 in exosomes and microparticles, respectively, for uptake by alveolar epithelial cells and subsequent inhibition of STAT activation. Secretion is tunable and occurs both in vitro and in vivo. SOCS secretion into lung lining fluid was diminished by cigarette smoking in humans and mice. Secretion and transcellular delivery of vesicular SOCS proteins thus represent a new model for the control of inflammatory signaling, which is subject to dysregulation during states of inflammation.
Clinical management of drug–drug interactions in HCV therapy: Challenges and solutions
Authors: David Burger, David Back, Peter Buggisch, Maria Buti, Antonio Craxí, Graham Foster, Hartwig Klinker, Dominique Larrey, Igor Nikitin, Stanislas Pol, Massimo Puoti, Manuel Romero-Gómez, Heiner Wedemeyer, Stefan Zeuzem
Journal: Journal of Hepatology (2012)

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug-drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug-drug interactions. Knowledge of pharmacokinetic profiles and concentration-effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.
Reply from Authors re: Ching-Shwun Lin, Tom F. Lue. Adipose-derived Stem Cells for the Treatment of Peyronie's Disease? Eur Urol 2013;63:561–2
Authors: Fabio Castiglione, Petter Hedlund, Frank Van der Aa, Trinity J. Bivalacqua, Patrizio Rigatti, Hein Van Poppel, Francesco Montorsi, Dirk De Ridder, Maarten Albersen
Journal: European Urology (2012)
Observed Benefit of Aflibercept in MCRC Patients ≥65 Years Old: Results of a Prespecified Age-Based Analysis of the Velour Study
Authors: Paul Ruff, David Ferry, Demetris Papamichael, Radek Lakomy, Jana Prausova, Guy van Hazel, Vladimir Moisyenko, Karen Soussan-Lazard, Pankaj Bhargava, Eric Van Cutsem, Teresa Macarulla
Journal: Annals of Oncology (2013)
Demonstration of structural polymorphism among HLA-DR light chains by two-dimensional gel electrophoresis.
Authors: D A Shackelford, J L Strominger
Journal: The Journal of Experimental Medicine (1980)

Human HLA-DR antigens were immunoprecipitated from Nonidet P-40 extracts of [35S]methionine-labeled B lymphoblastoid cell lines and compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF). Two-dimensional (2-D) gel analyses, combining SDS-PAGE in the first dimension and IEF in the second dimension, revealed that the heavy (alpha) and light (beta) chains of each DRw specificity displays microheterogeneity of charge. However, the pattern of the heavy chain did not vary among different DRw specificities. In contrast, the light chains of different DRw types varied both in apparent size and charge distribution. Removal of sialic acids with neuraminidase or inhibition of glycosylation with tunicamycin reduced the microheterogeneity of both DR subunits. However, the heavy and light chains each still focused as two major bands, suggesting that other post-translational modifications contribute to the microheterogeneity or that there are two nonallelic DR-like molecules. After treatment with either neuraminidase or tunicamycin, the DR light chains, but not the heavy chains, were still structurally polymorphic. The DR light chains of serologically cross-reactive specificities displayed similar 2-D gel patterns suggesting that the structural polymorphism of the DR light chains is the basis for the serologically detected polymorphism of the HLA-DR antigens. Two additional polypeptides were observed in immunoprecipitates of DR antigens. These proteins, designated M1 and M2, both had a basic isoelectric point and were invariant among different cell lines. The protein M1 may be intracellular because it can not be immunoprecipitated from the cell surface.