tbuckley/cabot-search huggingface dataset:
PC<sub>20</sub>Adenosine 5 ′ -Monophosphate Is More Closely Associated with Airway Inflammation in Asthma Than PC<sub>20</sub>Methacholine
Authors: MAARTEN Van Den BERGE, RONALD J. MEIJER, HUIB A. M. KERSTJENS, DOROTHEA M. de REUS, GERARD H. KOËTER, HENK F. KAUFFMAN, DIRKJE S. POSTMA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5 ′ -monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV1 to drop by 20% (PC20) is more closely associated with inflammatory parameters in asthma than PC20 methacholine. In 120 patients with atopic asthma (median FEV1 81% predicted [pred], median age 27 yr), PC20 methacholine and PC20 AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC20 methacholine was predominantly predicted by FEV1 %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC20 AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV1 %pred was only an additional independent predictor (total ev = 36%). PC20 AMP reflects more closely the extent of airway inflammation due to asthma than PC20 methacholine.
Cancer Cells Become Susceptible to Natural Killer Cell Killing after Exposure to Histone Deacetylase Inhibitors Due to Glycogen Synthase Kinase-3–Dependent Expression of MHC Class I–Related Chain A and B
Authors: Søren Skov, Marianne Terndrup Pedersen, Lars Andresen, Per Thor Straten, Anders Woetmann, Niels Ødum
Journal: Cancer Research (2005)

Abstract We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I–related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell–mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3 by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, γδ T cells, and CD8 T cells.
Great Books. My Adventures with Homer, Rousseau, Woolf, and Other Indestructible Writers of the Western World
Authors: David Danby
Journal: Annals of Internal Medicine (1997)

Updates1 December 1997Great Books. My Adventures with Homer, Rousseau, Woolf, and Other Indestructible Writers of the Western WorldDavid DanbyDavid DanbyNew York: Simon and Schuster; 1996Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-11-199712010-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I was almost ready to put my mother in a home, which would have been a defeat for all of us-almost the modern equivalent of Regan and Goneril's driving Lear out into the storm. But my wife Cathy was not. The neurologist's haughty manner so enraged her that she insisted my mother see another doctor-a young man, but one who knew something about geriatrics-and from the moment my mother entered the new doctor's office, the clouds began to lift. He quickly determined that she had an excess of calcium in her blood, a condition that her old doctor had wrongly ... Author, Article, and Disclosure InformationAuthors: David DanbyAffiliations: New York: Simon and Schuster; 1996 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHeterosexual Horror: Dracula, the Closet, and the Marriage-Plot 1 December 1997Volume 127, Issue 11Page: 1012KeywordsBenign tumorsBloodCalciumDementiaParathyroidStorms ePublished: 15 August 2000 Issue Published: 1 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nox2 NADPH Oxidase Promotes Pathologic Cardiac Remodeling Associated with Doxorubicin Chemotherapy
Authors: Youyou Zhao, Declan McLaughlin, Emma Robinson, Adam P. Harvey, Michelle B. Hookham, Ajay M. Shah, Barbara J. McDermott, David J. Grieve
Journal: Cancer Research (2010)

Doxorubicin is a highly effective cancer treatment whose use is severely limited by dose-dependent cardiotoxicity. It is well established that doxorubicin increases reactive oxygen species (ROS) production. In this study, we investigated contributions to doxorubicin cardiotoxicity from Nox2 NADPH oxidase, an important ROS source in cardiac cells, which is known to modulate several key processes underlying the myocardial response to injury. Nox2-deficient mice (Nox2-/-) and wild-type (WT) controls were injected with doxorubicin (12 mg/kg) or vehicle and studied 8 weeks later. Echocardiography indicated that doxorubicin-induced contractile dysfunction was attenuated in Nox2-/- versus WT mice (fractional shortening: 29.5±1.4 versus 25.7±1.0%; P<0.05). Similarly, in vivo pressure-volume analysis revealed that systolic and diastolic function was preserved in doxorubicin-treated Nox2-/- versus WT mice (ejection fraction: 52.6±2.5 versus 28.5±2.3%, LVdP/dtmin: -8,379±416 versus -5,198±527 mmHg s(-1); end-diastolic pressure-volume relation: 0.051±0.009 versus 0.114±0.012; P<0.001). Furthermore, in response to doxorubicin, Nox2-/- mice exhibited less myocardial atrophy, cardiomyocyte apoptosis, and interstitial fibrosis, together with reduced increases in profibrotic gene expression (procollagen IIIαI, transforming growth factor-β3, and connective tissue growth factor) and matrix metalloproteinase-9 activity, versus WT controls. These alterations were associated with beneficial changes in NADPH oxidase activity, oxidative/nitrosative stress, and inflammatory cell infiltration. We found that adverse effects of doxorubicin were attenuated by acute or chronic treatment with the AT1 receptor antagonist losartan, which is commonly used to reduce blood pressure. Our findings suggest that ROS specifically derived from Nox2 NADPH oxidase make a substantial contribution to several key processes underlying development of cardiac contractile dysfunction and remodeling associated with doxorubicin chemotherapy.
Cilostazol
Authors: Thomas Zeller, Dietmar Trenk
Journal: Circulation (2013)

I n the present multicenter, randomized, controlled Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) trial, Iida and colleagues 1 investigate the effect of cilostazol, which is chemically a quinolinone derivative, on the procedural and clinical outcome of femoropopliteal interventions.The major finding of the study is a significant 59% relative reduction of the 1-year restenosis rate as determined by angiography (20% in the cilostazol group versus 49% in the placebo group).It must be considered, however, that angiographic follow-up data were available in 80% of the cohort at 12 months.In addition, despite comparable hemodynamic improvement in both study cohorts at 1 year-secondary patency rates and ankle-brachial indexes were almost identical as a result of a significantly higher reintervention (target lesion revascularization) rate in the control cohort-patients had significantly improved clinical symptoms in the cilostazol cohort.
Associations between fluctuations in lung function and asthma control in two populations with differing asthma severity
Authors: C. Thamrin, R. Nydegger, G. Stern, P. Chanez, S. E. Wenzel, R. A. Watt, S. FitzPatrick, D. R. Taylor, U. Frey
Journal: Thorax (2011)

<h3>Background</h3> Lung function is a major criterion used to assess asthma control. Fluctuation analyses can account for lung function history over time, and may provide an additional dimension to characterise control. The relationships between mean and fluctuations in lung function with asthma control, exacerbation and quality of life were studied in two independent data sets. <h3>Methods</h3> Data from 132 adults with mild to moderate asthma and 159 adults with severe asthma were analysed separately. Fluctuations in twice-daily peak expiratory flow (PEF) over 6 months were measured by α, representing the strength of correlation with past lung function and potentially asthma stability. α and mean percentage predicted PEF (%predPEF) were plotted with and compared between patients grouped by asthma control defined by recent GINA (Global Initiative for Asthma) guidelines, the Asthma Control Questionnaire score, exacerbations and Asthma Quality of Life Questionnaire score. Associations of α and %predPEF with these outcomes were examined using multiple regression analyses. <h3>Results</h3> Both α and %predPEF differed with and were significantly associated with GINA-defined asthma control in both the mild to moderate and severe asthma groups. Only α was related to whether or not exacerbations occurred in mild to moderate asthma, while %predPEF was more significantly related than α in severe asthma. In those with severe asthma, only %predPEF was significantly related to Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. <h3>Conclusion</h3> Lung function history quantified by fluctuation analysis provides additional information to mean lung function, and may help characterise the current state of asthma control. It may also potentially aid in phenotyping clinical asthma.
Breathing pattern and carbon dioxide retention in severe chronic obstructive pulmonary disease.
Authors: M. Gorini, G. Misuri, A. Corrado, R. Duranti, I. Iandelli, E. De Paola, G. Scano
Journal: Thorax (1996)

BACKGROUND: The factors leading to chronic hypercapnia and rapid shallow breathing in patients with severe chronic obstructive pulmonary disease (COPD) are not completely understood. In this study the interrelations between chronic carbon dioxide retention, breathing pattern, dyspnoea, and the pressure required for breathing relative to inspiratory muscle strength in stable COPD patients with severe airflow obstruction were studied. METHODS: Thirty patients with COPD in a clinically stable condition with forced expiratory volume in one second (FEV1) of &lt; 1 litre were studied. In each patient the following parameters were assessed: (1) dyspnoea scale rating, (2) inspiratory muscle strength by measuring minimal pleural pressure (PPLmin), and (3) tidal volume (VT), flow, pleural pressure swing (PPLsw), total lung resistance (RL), dynamic lung elastance (ELdyn), and positive end expiratory alveolar pressure (PEEPi) during resting breathing. RESULTS: Arterial carbon dioxide tension (PaCO2) related directly to RL/PPLmin, and ELdyn/PPLmin, and inversely to VT and PPLmin. There was no relationship between PaCO2 and functional residual capacity (FRC), total lung capacity (TLC), or minute ventilation. PEEPi was similar in eucapnic and hypercapnic patients. Expressing PaCO2 as a combined function of VT and PPLmin (stepwise multiple regression analysis) explained 71% of the variance in PaCO2. Tidal volume was directly related to inspiratory time (TI), and TI was inversely related to the pressure required for breathing relative to inspiratory muscle strength (PPLsw, %PPLmin). There was an association between the severity of dyspnoea and both the increase in PPLsw (%PPLmin) and the shortening in TI. CONCLUSIONS: The results indicate that, in stable patients with COPD with severe airflow obstruction, hypercapnia is associated with shallow breathing and inspiratory muscle weakness, and rapid and shallow breathing appears to be linked to both a marked increase in the pressure required for breathing relative to inspiratory muscle strength and to the severity of the breathlessness.
Long-Term Benefits with Sirolimus-Based Therapy after Early Cyclosporine Withdrawal
Authors: Henri Kreis, Rainer Oberbauer, Josep M. Campistol, Timothy Mathew, Pierre Daloze, Francesco P. Schena, James T. Burke, Yves Brault, Martine Gioud-Paquet, Joseph A. Scarola, John F. Neylan
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Graft function at 6 or 12 mo is positively correlated with renal transplant survival. The 36-mo results of a study that tested whether withdrawing cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would affect renal graft survival are reported. Eligible patients (<i>n</i> = 430) who were receiving SRL-CsA-ST were randomly assigned at 3 mo to remain on SRL-CsA-ST or to have CsA withdrawn (SRL-ST group). At 36 mo, the calculated GFR was significantly better with SRL-ST (47.3 <i>versus</i> 59.4 ml/min; <i>P</i> &lt; 0.001) as was the slope of the GFR (−3.6 <i>versus</i> 0.8 ml/min; <i>P</i> &lt; 0.001). This was accompanied by growing trend for improved graft survival in the SRL-ST group (85.1% <i>versus</i> 91.2%, <i>P</i> = 0.052 at 36 mo; 81.4% <i>versus</i> 91.2%, <i>P</i> = 0.015 in a cumulative data analysis up to 54 mo), despite numerically more biopsy-proven acute rejections after randomization (5.6% <i>versus</i> 10.2%; <i>P</i> = 0.107). Lipid parameters were similar between groups, whereas both systolic and diastolic BP were significantly lower in the SRL-ST group. Investigator-reported hypertension, abnormal kidney function, edema, hyperuricemia, hyperkalemia, gingival hyperplasia, and <i>Herpes zoster</i> occurred significantly more often in SRL-CsA-ST patients. Abnormal liver function test results, hypokalemia, thrombocytopenia, and abnormal healing were reported significantly more often with SRL-ST. The discontinuation rate was significantly higher for SRL-CsA-ST (48% <i>versus</i> 38%; <i>P</i> = 0.041). In conclusion, withdrawing CsA from a SRL-CsA-ST regimen at 3 mo after transplantation resulted in long-term benefits for renal transplant recipients.
Morning Handover of On-Call Issues
Authors: Megan K. Devlin, Natalie K. Kozij, Alex Kiss, Lisa Richardson, Brian M. Wong
Journal: JAMA Internal Medicine (2014)

Handover is the process of transferring pertinent patient information and clinical responsibility between health care practitioners. Few studies have examined morning handover from the overnight trainee to the daytime team.To characterize current morning handover practices in 2 academic medical centers by assessing the frequency of omissions of clinically important overnight issues during morning handover and identifying factors that influence the occurrence of such omissions.A prospective, point-prevalence study was conducted in the general internal medicine wards of 2 tertiary care academic medical centers in Toronto, Ontario, Canada, in 2012 and 2013. Participants included on-call third-year medical students and first- and second-year residents.Completeness of morning handover of clinically important overnight issues identified using a targeted medical records review and processes of morning handover characterized by direct observation.We identified 141 clinically important overnight issues during 26 days of observation. The on-call trainee omitted 40.4% (95% CI, 32.3%-48.5%) of clinically important issues during morning handover and did not document any information in the patient's medical record for 85.8% (95% CI 80.1%-91.6%) of these issues. By univariate analysis, running the list patient-by-patient (ie, the entire team discusses each patient) (OR, 4.32; 95% CI, 1.94-9.60; P < .001) and using a dedicated handover location (OR, 2.61; 95% CI, 1.30-5.22; P = .007) positively correlated with handover of an issue taking place, whereas distractions in the meeting area inversely correlated with the likelihood of handover of an issue taking place (OR, 0.96 for every increase in 1 distraction; 95% CI, 0.93-0.98; P = .002). Using a multivariate mixed-effects model, only running the list remained as an independent predictor of the handover of an issue (OR, 3.80; 95% CI, 1.25-11.49; P = .02).On-call trainees omit numerous clinically important issues when handing over to the daytime team. Training programs should introduce educational activities and workflow changes, and provide dedicated time and a distraction-free environment, to improve handover of on-call issues.
Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats
Authors: Jennifer Altomonte, Rickmer Braren, Stephan Schulz, Sabrina Marozin, Ernst J. Rummeny, Roland M. Schmid, Oliver Ebert
Journal: Hepatology (2008)

Abstract Oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. We have reported previously that recombinant vesicular stomatitis virus (VSV) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat multifocal hepatocellular carcinoma (HCC), resulting in tumor necrosis and prolonged survival. Though the results were encouraging, complete tumor regression was not observed, which led us to explore alternative approaches to further enhance the efficacy of VSV treatment. Transarterial embolization techniques have been shown to improve the efficiency and tumor selectivity of anticancer treatments. Degradable starch microspheres (DSM) are one such embolic agent that provides transient embolization of the therapeautic agent before being degraded by serum amylases. Here we demonstrate via dynamic contrast-enhanced magnetic resonance imaging that in our rat model of multifocal HCC, DSM injection into the hepatic artery results in a substantial reduction in tumor perfusion of systemically applied contrast agent. VSV, when administered in combination with DSM, results in enhanced tumor necrosis and synergistically prolongs survival when compared with VSV or DSM monotherapy. Conclusion: This regimen of viroembolization represents an innovative therapeutic modality that can augment the future development of transarterial oncolytic virus therapy for patients with advanced HCC. (Hepatology 2008;48:1864-1873.)
The vasculature of the carotid body
Authors: D. HEATH, R. JAGO, P. SMITH
Journal: Cardiovascular Research (1983)

A histological and electron microscopical study was carried out on the vasculature of the carotid bodies in seven subjects coming to necropsy. None of these had suffered from chronic hypoxaemia or systemic hypertension during life and none had hypertrophy of the right or left ventricle. The vasculature of the carotid bodies showed three distinct components. There was a proximal portion, comprising elastic interlobular arteries, which had a wall in which elastic tissue predominated and in which many nerve fibrils could be demonstrated. This is considered to be baroreceptor in nature. There was an intermediate portion comprising muscular intralobular arterioles which are believed to be capable of controlling the level of blood supply to the parenchyma of the carotid bodies. Finally there are glomic capillaries surrounded by elongated pericytes and sustentacular cells. One or other of these elongated cells is thought to be responsible for the carotid body hyperplasia which is associated with systemic hypertension and states of chronic hypoxaemia.
Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy
Authors: David M. Nathan, John B. Buse, Mayer B. Davidson, Ele Ferrannini, Rury R. Holman, Robert Sherwin, Bernard Zinman
Journal: Diabetes Care (2007)

The consensus algorithm for the management of type 2 diabetes was developed on behalf of the American Diabetes Association and the European Association for the Study of Diabetes approximately 1 year ago (1,2). This evidence-based algorithm was developed to help guide health care providers to choose the most appropriate treatment regimens from an ever-expanding list of approved medications. The authors continue to endorse the major features of the algorithm, including the need to achieve and maintain glycemia within or as close to the nondiabetic range as is safely possible, the initiation of lifestyle interventions and treatment with metformin at the time of diagnosis, the rapid addition of medications and transition to new regimens when target glycemia is not achieved, and the early addition of insulin therapy in patients who do not meet target A1C levels.

The availability of newly approved medications and the accrual of new clinical trial and other data should inform the algorithm. In this update, we primarily address one important issue that has received much recent attention: our current understanding of the advantages and disadvantages of the thiazolidinediones. In addition, we have revised the original Table 1 to include the dipeptidylpeptidase-4 inhibitor sitagliptin, which was not approved by the U.S. Food and Drug Administration at the time of our original publication (Table 1).

We are mindful of the importance of not changing this consensus guideline in …
Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study
Authors: Ronac Mamtani, Kevin Haynes, Warren B. Bilker, David J. Vaughn, Brian L. Strom, Karen Glanz, James D. Lewis
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD.
2013 ACCF/AHA Key Data Elements and Definitions for Measuring the Clinical Management and Outcomes of Patients With Acute Coronary Syndromes and Coronary Artery Disease
Authors: Christopher P. Cannon, Ralph G. Brindis, Bernard R. Chaitman, David J. Cohen, J. Thomas Cross, Joseph P. Drozda, Francis M. Fesmire, Dan J. Fintel, Gregg C. Fonarow, Keith A. Fox, Darryl T. Gray, Robert A. Harrington, Karen A. Hicks, Judd E. Hollander, Harlan Krumholz, Darwin R. Labarthe, Janet B. Long, Alice M. Mascette, Connie Meyer, Eric D. Peterson, Martha J. Radford, Matthew T. Roe, James B. Richmann, Harry P. Selker, David M. Shahian, Richard E. Shaw, Sharon Sprenger, Robert Swor, James A. Underberg, Frans Van de Werf, Bonnie H. Weiner, William S. Weintraub
Journal: Journal of the American College of Cardiology (2013)