tbuckley/cabot-search huggingface dataset:
Update in Cardiology
Authors: Elliot Rapaport
Journal: Annals of Internal Medicine (2004)

Updates from the Annual Session3 February 2004Update in CardiologyElliot Rapaport, MDElliot Rapaport, MDFrom San Francisco General Hospital and University of California, San Francisco, San Francisco, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-3-200402030-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This year's Update in Cardiology focuses on heart failure, acute coronary syndromes, hypertension, and low-density lipoprotein (LDL) cholesterol lowering. The newer clinical trials in these fields are changing approaches to cardiac care.Heart FailureSeveralrecent trials have confirmed the value of β-blockers and showed that internal defibrillation and ventricular resynchronization significantly reduce mortality in post–myocardial infarction (MI) patients. However, physicians should not allow these new developments to distract them from adhering to proven treatments for patients with heart failure. A recent study of 180 community hospitals nationwide showed that drugs of proven effectiveness in reducing heart failure mortality, such as ...References1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13-20. [PMID: 12517460] CrossrefMedlineGoogle Scholar2. Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, et al . A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-92. [PMID: 12584366] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From San Francisco General Hospital and University of California, San Francisco, San Francisco, California.Contributing Editor: Jennifer Fisher Wilson.Disclosures: None disclosed.Corresponding Author: Elliot Rapaport, MD, Cardiology Division, Room 5G1, San Francisco General Hospital, 1001 Potrero Street, San Francisco, CA 94110; e-mail, [email protected]ucsf.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 February 2004Volume 140, Issue 3Page: 203-210KeywordsACE inhibitorsAnginaBlood pressureHeart failureMagnesiumMortalityMyocardial infarctionPercutaneous coronary interventionRelative riskStroke ePublished: 3 February 2004 Issue Published: 3 February 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Pilot Study of Fecal Serine-Protease Activity: A Pathophysiologic Factor in Diarrhea-Predominant Irritable Bowel Syndrome
Authors: Richárd Róka, András Rosztóczy, Mathilde Leveque, Ferenc Izbéki, Ferenc Nagy, Tamás Molnár, János Lonovics, Rafael Garcia–Villar, Jean Fioramonti, Tibor Wittmann, Lionel Bueno
Journal: Clinical Gastroenterology and Hepatology (2007)
FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer
Authors: K. Tamura, C. Shimizu, T. Hojo, S. Akashi-Tanaka, T. Kinoshita, K. Yonemori, T. Kouno, N. Katsumata, M. Ando, K. Aogi, F. Koizumi, K. Nishio, Y. Fujiwara
Journal: Annals of Oncology (2010)
Prostate Cancer Risk and Serum Levels of Insulin and Leptin: a Population-Based Study
Authors: A. W. Hsing, S. Chua, Y.-T. Gao, E. Gentzschein, L. Chang, J. Deng, F. Z. Stanczyk
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: In a previous study of Chinese men, we found that men with a higher waist-to-hip ratio (WHR) have a higher prostate cancer risk. Because leptin and insulin are related to body fat distribution, we examined whether leptin and insulin were associated with prostate cancer risk. Methods: Blood samples were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects randomly selected from residents of Shanghai, China. Epidemiologic information and anthropometric measurements were collected in personal interviews. Serum leptin, insulin, and sex hormone levels were measured by radioimmunoassay, and insulin-like growth factor-I (IGF-I) was measured by enzyme-linked immunosorbent assay. Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels. All statistical tests were two-sided. Results: After adjustment for body mass index, WHR, IGF-I, and sex hormone levels, higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer (P<.001). Men in the highest tertile of insulin levels had a 2.56-fold (95% confidence interval [CI] = 1.38 to 4.75) risk of prostate cancer compared with men in the lowest tertile. Regardless of the tertile level of WHR, higher serum insulin levels were associated with an increased risk of prostate cancer: Men in the highest tertiles of WHR (>0.900) and insulin (>8.83 μU/mL) had 8.55 times (95% CI = 2.80 to 26.10) the prostate cancer risk of men in the lowest tertiles of both, and those in the lowest tertile of WHR (<0.873) and highest tertile of insulin had 4.30 times (95% CI = 1.17 to 15.70) the risk. By contrast, the association between leptin levels and prostate cancer risk was not statistically significant. Conclusion: Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men. Further research, especially prospective studies, is needed to confirm these findings in high-risk populations and to clarify the underlying mechanisms involved.
Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function
Authors: Anastasia M. Wengrowski, Xin Wang, Srinivas Tapa, Nikki Gillum Posnack, David Mendelowitz, Matthew W. Kay
Journal: Cardiovascular Research (2014)

AimsRelease of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function.
Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy
Authors: C. Twelves, W. Scheithauer, J. McKendrick, J.-F. Seitz, G. Van Hazel, A. Wong, E. Díaz-Rubio, F. Gilberg, J. Cassidy
Journal: Annals of Oncology (2011)

This multicenter randomized trial compared oral capecitabine with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer.
Factors Influencing Canine Mammary Cancer Development and Postsurgical Survival&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Schneider, C R Dorn, D O Taylor
Journal: JNCI Journal of the National Cancer Institute (1969)

A retrospective study was conducted involving canine mammary cancer cases and age- and breed-matched controls. Only histologically confirmed malignant mammary cases were used. Of these, 71 were diagnosed as adenocarcinomas and 22 as malignant mixed mammary tumors. There were 87 case-controlled matches. Factors studied were classified within the categories of neutering, estrus, pseudopregnancy, parity, fecundity, and postsurgical survival. Within the scope of these variables, there were no differences in effects on the occurrence of adenocarcinomas or malignant mixed mammary tumors. Among the variables, neutered bitches had 12% of the mammary cancer risk as compared to intact animals. Bitches spayed before any estrous cycles had approximately 0.5% of the mammary cancer risk; those that had only 1 estrous cycle had 8%, and animals that had 2 or more estrous cycles before neutering, 26%. Within the group having 2 or more estrous cycles before being spayed, those neutered before 2½ years of age exhibited a marked sparing effect on mammary cancer risk not shown for bitches neutered after 2½ years of age. Tests of various factors within the categories of pseudopregnancy, parity, and fecundity indicated no significant effects on mammary cancer risk. Survival data, based on observation for a minimum of 42 months after surgical removal of the cancer, indicated excess mortality due to mammary cancer was concentrated in the first year; 2½ times more dogs died, either naturally or by euthanasia, than expected. Apparently the younger an animal at the time of cancer surgery, the more apt it was to survive. Neutering after cancer diagnosis did not affect either survival or cause of death. The age distribution of mammary cancer in female dogs was compared to the age distribution of breast cancer in women. Mammary cancer in the bitch mimics that of human breast cancer, except that the dog, after maturity, ages at 4 times the rate of humans. This age similarity and the common sparing effect of neutering in the 2 species provide strong support for the use of canine mammary cancer as a research model for breast cancer in women.
Insulin-degrading enzyme is exported via an unconventional protein secretion pathway
Authors: Ji Zhao, Lilin Li, Malcolm A Leissring
Journal: Molecular Neurodegeneration (2009)

Abstract Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc-metalloprotease that degrades several pathophysiologically significant extracellular substrates, including insulin and the amyloid β-protein (Aβ), and accumulating evidence suggests that IDE dysfunction may be operative in both type 2 diabetes mellitus and Alzheimer disease (AD). Although IDE is well known to be secreted by a variety of cell types, the underlying trafficking pathway(s) remain poorly understood. To address this topic, we investigated the effects of known inhibitors or stimulators of protein secretion on the secretion of IDE from murine hepatocytes and HeLa cells. IDE secretion was found to be unaffected by the classical secretion inhibitors brefeldin A (BFA), monensin, or nocodazole, treatments that readily inhibited the secretion of α1-antitrypsin (AAT) overexpressed in the same cells. Using a novel cell-based Aβ-degradation assay, we show further that IDE secretion was similarly unaffected by multiple stimulators of protein secretion, including glyburide and 3'-O-(4-benzoyl)benzoyl-ATP (Bz-ATP). The calcium ionophore, A23187, increased extracellular IDE activity, but only under conditions that also elicited cytotoxicity. Our results provide the first biochemical evidence that IDE export is not dependent upon the classical secretion pathway, thereby identifying IDE as a novel member of the select class of unconventionally secreted proteins. Further elucidation of the mechanisms underlying IDE secretion, which would be facilitated by the assays described herein, promises to uncover processes that might be defective in disease or manipulated for therapeutic benefit.
I<scp>mmunity to</scp>T<scp>uberculosis</scp>
Authors: Robert J. North, Yu-Jin Jung
Journal: Annual Review of Immunology (2004)

▪ Abstract Only 5 to 10% of immunocompetent humans are susceptible to tuberculosis, and over 85% of them develop the disease exclusively in the lungs. Human immunodeficiency virus (HIV)-infected humans, in contrast, can develop systemic disease that is more quickly lethal. This is in keeping with other evidence showing that susceptible humans generate some level of Th1 immunity to Mycobacterium tuberculosis (Mtb) infection. Tuberculosis in mice is also exclusively a lung disease that is progressive and lethal, in spite of the generation of Th1-mediated immunity. Thus mouse tuberculosis is a model of tuberculosis in susceptible humans, as is tuberculosis in guinea pigs and rabbits. Inability to resolve infection and prevent disease may not be a consequence of the generation of an inadequate number of Th1 cells but of an intrinsic deficiency in macrophage function that prevents these cells from expressing immunity. If this proves to be true, vaccinating susceptible humans against tuberculosis will be a difficult task.
Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma
Authors: M. Silvestri
Journal: Thorax (2000)

Bronchial hyperresponsiveness and airway inflammation are distinctive features of asthma. Evaluation of nitric oxide (NO) levels in expired air have been proposed as a reliable method for assessing the airway inflammatory events in asthmatic subjects. A study was undertaken to evaluate whether airway hyperresponsiveness is related to levels of exhaled NO.Thirty two steroid-naive atopic children with mild intermittent asthma of mean (SD) age 11.8 (2.3) years and 28 age matched healthy controls were studied to investigate whether baseline lung function or airway hyperresponsiveness is related to levels of exhaled NO. Airway responsiveness was assessed as the dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV(1)) from control (PD(20) methacholine) and exhaled NO levels were measured by chemiluminescence analysis of exhaled air.At baseline asthmatic children had significantly higher NO levels than controls (mean difference 25.87 ppb (95% CI 18.91 to 32.83); p<0.0001) but there were no significant differences in lung function parameters (forced vital capacity (FVC), FEV(1) (% pred), and forced expiratory flows at 25-75% of vital capacity (FEF(25-75%))). In the asthmatic group exhaled NO levels were not significantly correlated with baseline lung function values or PD(20) methacholine.These results suggest that levels of exhaled NO are not accurate predictors of the degree of airway responsiveness to inhaled methacholine in children with mild intermittent asthma.
A Comprehensive Nationwide Study of the Incidence Rate and Lifetime Risk for Treated Mental Disorders
Authors: Carsten Bøcker Pedersen, Ole Mors, Aksel Bertelsen, Berit Lindum Waltoft, Esben Agerbo, John J. McGrath, Preben Bo Mortensen, William W. Eaton
Journal: JAMA Psychiatry (2014)

IMPORTANCEUnderstanding the epidemiologic profile of the life course of mental disorders is fundamental for research and planning for health care.Although previous studies have used population surveys, informative and complementary estimates can be derived from population-based registers.OBJECTIVE To derive comprehensive and precise estimates of the incidence rate of and lifetime risk for any mental disorder and a range of specific mental disorders. DESIGN, SETTING, AND PARTICIPANTSWe conducted a follow-up study of all Danish residents (5.6 million persons), to whom all treatment is provided by the government health care system without charge to the patient, from January 1, 2000, through December 31, 2012 (total follow-up, 59.5 million person-years).During the study period, 320 543 persons received first lifetime treatment in a psychiatric setting for any mental disorder; 489 006 persons were censored owing to death; and 69 987 persons were censored owing to emigration.Specific categories of mental disorders investigated included organic mental disorders, substance abuse disorders, schizophrenia, mood disorders,
Accuracy of endoscopic ultrasonography in diagnosing ascites and predicting peritoneal metastases in gastric cancer patients
Authors: Y T Lee
Journal: Gut (2005)

Preoperative diagnosis of peritoneal metastases (PM) is difficult in patients with gastric cancer (GC).To assess the accuracy of endoscopic ultrasonography (EUS) in diagnosing ascites and its predictability for the presence of PM in GC patients.Consecutive patients with newly diagnosed GC from 1998 to 2004 were studied.All patients underwent EUS, ultrasound (US), and computed tomography (CT) scan for preoperative staging and the presence of ascites. The results were compared with operative findings. The diagnosis of PM was confirmed by histopathology or peritoneal fluid cytology.A total of 301 patients were recruited and in 250 patients the presence of ascites (n = 93) and PM (n = 71) were confirmed. EUS was more sensitive (87.1%) than combined US and CT scan examinations (16.1%) and operative findings (laparoscopy or laparotomy) (40.9%) in diagnosing ascites. Sensitivity, specificity, positive and negative predictive values, and accuracy for predicting the presence of PM were 73%, 84%, 64%, 89%, and 81% by EUS; 18%, 99%, 87%, 75%, and 76% by combining US and CT scan; and 77%, 94%, 83%, 91%, and 89% by operative findings, respectively. In multivariate logistic regression analysis, EUS detected ascites was the only significant independent predictor for the presence of PM (p<0.001; odds ratio 4.7 (95% confidence interval 2.0-11.2)).EUS is a sensitive method for diagnosing ascites which is an important predictive factor for the presence of PM in GC patients.
Cetuximab in Combination With Chemoradiotherapy Before Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma: A Prospective, Multicenter Phase IB/II Trial (SAKK 75/06)
Authors: Thomas Ruhstaller, Miklos Pless, Daniel Dietrich, Helmut Kranzbuehler, Roger von Moos, Peter Moosmann, Michael Montemurro, Paul M. Schneider, Daniel Rauch, Oliver Gautschi, Walter Mingrone, Lucas Widmer, Roman Inauen, Peter Brauchli, Viviane Hess
Journal: Journal of Clinical Oncology (2011)

This multicenter phase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer.Patients with resectable, locally advanced esophageal cancer received two 3-week cycles of induction chemoimmunotherapy (cisplatin 75 mg/m(2) day 1, docetaxel 75 mg/m(2) day 1, cetuximab 250 mg/m(2) days 1, 8,15 [400 mg/m(2) loading dose]) followed by chemoimmunoradiation therapy (CIRT) and surgery. CIRT consisted of 45 Gy radiotherapy (RT) plus concurrent cisplatin 25 mg/m(2) and cetuximab 250 mg/m(2) weekly for 5 weeks in cohort 1. If fewer than three of seven patients experienced limiting toxicity (LT), the next seven patients also received docetaxel (20 mg/m(2) weekly × 5). If fewer than three patients experienced LTs, 13 additional patients were treated at this dose.In total, 28 patients (median age, 64 years) with predominantly node-positive (82%) esophageal adenocarcinoma (15 patients) or squamous cell carcinoma (13 patients) were enrolled and 24 (86%) completed the entire trimodal therapy. During CIRT, no LT occurred, rash was not exacerbated within the RT field, and the main grade 3 toxicities were esophagitis (seven patients), anorexia (three), fatigue (three), and thrombosis (two). Surgery (R0 resection) was performed in 25 patients. Anastomotic leakage occurred in three patients: two recovered spontaneously and one successfully underwent re-operation. There were no deaths at 30 days and no treatment-related mortality after 12 months. Nineteen patients (68%) showed complete or near complete pathologic regression.Adding cetuximab to preoperative chemoradiotherapy is feasible without increasing postoperative mortality. Phase III investigation has begun based on the high histopathologic response and R0 resection rate.
Essential Evidence-Based Medicine
Authors: Kristina Fister
Journal: BMJ (2005)

A lmost every textbook about evidence based medicine (EBM) starts with its definition, and that is usually when I roll my eyes and quickly turn the page. Of course, I always go back and read the piece, because I love EBM. But why is it that we still need to define it? It is now about 20 years old and by most relevant medical professionals acknowledged as the way to practise and advance in today's …
Meta-Analysis of Genome-Wide Association Studies in &gt;80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
Authors: Abbas Dehghan, Josée Dupuis, Maja Barbalic, Joshua C. Bis, Gudny Eiriksdottir, Chen Lu, Niina Pellikka, Henri Wallaschofski, Johannes Kettunen, Peter Henneman, Jens Baumert, David P. Strachan, Christian Fuchsberger, Veronique Vitart, James F. Wilson, Guillaume Paré, Silvia Naitza, Megan E. Rudock, Ida Surakka, Eco J.C. de Geus, Behrooz Z. Alizadeh, Jack Guralnik, Alan Shuldiner, Toshiko Tanaka, Robert Y.L. Zee, Renate B. Schnabel, Vijay Nambi, Maryam Kavousi, Samuli Ripatti, Matthias Nauck, Nicholas L. Smith, Albert V. Smith, Jouko Sundvall, Paul Scheet, Yongmei Liu, Aimo Ruokonen, Lynda M. Rose, Martin G. Larson, Ron C. Hoogeveen, Nelson B. Freimer, Alexander Teumer, Russell P. Tracy, Lenore J. Launer, Julie E. Buring, Jennifer F. Yamamoto, Aaron R. Folsom, Eric J.G. Sijbrands, James Pankow, Paul Elliott, John F. Keaney, Wei Sun, Antti-Pekka Sarin, João D. Fontes, Sunita Badola, Brad C. Astor, Albert Hofman, Anneli Pouta, Karl Werdan, Karin H. Greiser, Oliver Kuss, Henriette E. Meyer zu Schwabedissen, Joachim Thiery, Yalda Jamshidi, Ilja M. Nolte, Nicole Soranzo, Timothy D. Spector, Henry Völzke, Alexander N. Parker, Thor Aspelund, David Bates, Lauren Young, Kim Tsui, David S. Siscovick, Xiuqing Guo, Jerome I. Rotter, Manuela Uda, David Schlessinger, Igor Rudan, Andrew A. Hicks, Brenda W. Penninx, Barbara Thorand, Christian Gieger, Joe Coresh, Gonneke Willemsen, Tamara B. Harris, Andre G. Uitterlinden, Marjo-Riitta Järvelin, Kenneth Rice, Dörte Radke, Veikko Salomaa, Ko Willems van Dijk, Eric Boerwinkle, Ramachandran S. Vasan, Luigi Ferrucci, Quince D. Gibson, Stefania Bandinelli, Harold Snieder, Dorret I. Boomsma, Xiangjun Xiao, Harry Campbell, Caroline Hayward, Peter P. Pramstaller, Cornelia M. van Duijn, Leena Peltonen, Bruce M. Psaty, Vilmundur Gudnason, Paul M. Ridker, Georg Homuth, Wolfgang Koenig, Christie M. Ballantyne, Jacqueline C.M. Witteman, Emelia J. Benjamin, Markus Perola, Daniel I. Chasman
Journal: Circulation (2011)

C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.