tbuckley/cabot-search huggingface dataset:
Tadalafil for Prevention of Erectile Dysfunction After Radiotherapy for Prostate Cancer
Authors: Thomas M. Pisansky, Stephanie L. Pugh, Richard E. Greenberg, Nadeem Pervez, Daniel R. Reed, Seth A. Rosenthal, Rex B. Mowat, Adam Raben, Mark K. Buyyounouski, Lisa A. Kachnic, Deborah W. Bruner
Journal: JAMA (2014)

Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined.To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected.Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013.One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year.Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events.Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P = .49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners.Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients.clinicaltrials.gov Identifier: NCT00931528.
Methadone Maintenance Programs in Sweden
Authors: Olof Blix
Journal: JAMA (1989)

To the Editor. —  I write this letter as the medical director of one of the two methadone maintenance treatment programs currently active and caring for former heroin addicts in Sweden. I was invited to give the keynote address at the opening session of the 5th Annual Northeastern Regional Methadone Maintenance Conference in New York on November 28, 1988. I was deeply concerned when my audience in New York showed me the article in the November 25 issue of JAMA stating that Sweden has effectively banned it, after closing the country's single program, referring to methadone maintenance treatment. 1   The facts are that our (then sole) methadone maintenance program in Uppsala, Sweden, was closed temporarily for admittance of new patients from 1979 to 1984, which was disastrous to the 98 heroin addicts on the waiting list: 39 (40%) died during that period (drug-related deaths). Conversely, the patients who had been
Intravascular Stents to Prevent Occlusion and Re-Stenosis after Transluminal Angioplasty
Authors: Ulrich Sigwart, Jacques Puel, Velimir Mirkovitch, Francis Joffre, Lukas Kappenberger
Journal: New England Journal of Medicine (1987)

Occlusion and re-Stenosis are the most common reasons that transluminal balloon angioplasty may fail to provide long-term benefit. An intravascular mechanical support was therefore developed with the aim of preventing re-Stenosis and sudden closure of diseased arteries after angioplasty. The endoprosthesis consists of a self-expandable stainless-steel mesh that can be implanted nonsurgically in the coronary or peripheral arteries. Experiments in animals showed complete intimal coverage within weeks and no late thrombosis during a follow-up period of up to one year. We performed 10 implantations in 6 patients for iliac or femoral arterial disease; 24 coronary-artery stents were implanted in 19 patients who presented with coronary-artery restenoses (n = 17) or abrupt closure (n = 4) after transluminal angioplasty or deterioration of coronarybypass grafts (n = 3). We observed three complications in the group with coronary disease. One thrombotic occlusion of a stent resulted in asymptomatic closure, a second acute thrombosis was managed successfully with thrombolysis, and one patient died after bypass surgery for a suspected but unfound occlusion. follow-up in the patients has continued for nine months without evidence of any further restenoses within the stented segments. Our preliminary experience suggests that this vascular endoprosthesis may offer a useful way to prevent occlusion and re-Stenosis after transluminal angioplasty. long-term follow-up will be required to validate the early success of this procedure. (N Engl J Med 1987; 316:701–6.)
Rat liver endothelial cells have a greater capacity than kupffer cells to endocytoseN-acetylglucosamine- and mannose-terminated glycoproteins
Authors: Danielle P. Praaning-Van Dalen, Margreet A. De Leeuw, A. Brouwer, Dick L. Knook
Journal: Hepatology (1987)

The capacity of rat liver Kupffer and endothelial cells to endocytose glycoproteins with N -acetylglucosamine-or mannose-terminated oligosaccharide chains was studied. For this purpose, agalactoorosomucoid, ahexo-saminoorosomucoid and horseradish peroxidase were used as ligands. A reliable determination of the amount of ligand endocytosed in vivo or in vitro was made possible by using the recently developed cold pronase method for the isolation and purification of Kupffer and endothelial cells. Both cell types participated in the uptake of the ligands in vivo as well as in vitro , but their endocytic capacity was several times greater in vivo than in vitro . Under both conditions, endothelial cells possessed a greater capacity to endocytose the ligands than did Kupffer cells. Since the total number of endothelial cells in the liver is at least twice the number of Kupffer cells, the contribution of endothelial cells to the liver uptake of N -acetylglucosamine-terminated glycoproteins in vivo was estimated to be 3 to 7 times higher than that of the Kupffer cells. In vitro experiments showed that the uptake of the glycoproteins followed saturation kinetics and was strongly inhibited at 4±C and in the presence of mannan. Ultrastructural investigations revealed that horseradish peroxidase was taken up by all Kupffer and endothelial cells. These results emphasize the important role liver endothelial cells play in the clearance of specific glycoproteins from the circulation.
THE EARLY REPOLARIZATION PATTERN: CLINICAL CORRELATES AND HERITABILITY
Authors: Peter Noseworthy, Kimmo Porthan, Jani Tikkanen, Gina Peloso, Faisal Merchant, Arto Pietila, Aki Havulinna, Lasse Oikarinen, Shi-Jen Hwang, Christopher O'Donnell, Veikko Salomaa, Christopher Newton-Cheh, Heikki Huikuri
Journal: Journal of the American College of Cardiology (2011)
Release of prostacyclin from the human aorta
Authors: V TSANG, J Y JEREMY, D P MIKHAILIDIS, R K WALESBY, J C WRIGHT, P DANDONA
Journal: Cardiovascular Research (1988)

Prostacyclin (PGI2) release by human aortic tissue obtained at surgery was assessed in patients (n = 23) with ischaemic heart disease undergoing coronary artery bypass grafting (group 1) patients (n = 14) undergoing surgery for aortic stenosis (group 2), patients (n = 4) undergoing surgery for aortic regurgitation (group 3), and patients (n = 8) with ischaemic heart disease taking aspirin (group 4). Although there was a highly significant correlation between (a) intimal and medial PGI2 production and (b) medial PGI2 production and aortic diameter, there was no correlation between intimal PGI2 production and aortic diameter. Aspirin intake (75-150 mg daily) was associated with a pronounced inhibition (95%) of aortic PGI2 production. This inhibition of aortic PGI2 secretion by aspirin may account for the variable efficiency of aspirin in altering the natural history of vascular disease.
Detection and estimation of the degree of mitral regurgitation by range-gated pulsed doppler echocardiography.
Authors: A S Abbasi, M W Allen, D DeCristofaro, I Ungar
Journal: Circulation (1980)

Sensitivity and specificity of detection of mitral regurgitation was assessed by range-gated Doppler echocardiography. The degree of mitral regurgitation was also estimated by the depth and width of the regurgitant jet detected with Doppler and compared with that assessed by left ventriculography. Of 47 patients with an adequate Doppler study, 24 had no mitral regurgitation by ventriculography. All but one were also negative for mitral regurgitation by Doppler, for a specificity of 96%. Of 23 cases with mitral regurgitation documented by ventriculography, Doppler detected mitral regurgitation in 21, for a sensitivity of 92%. Two cases with mitral regurgitation undiagnosed by Doppler had mild mitral regurgitation due to papillary muscle dysfunction. All cases with rheumatic mitral regurgitation were detected. The degree of mitral regurgitation estimated with Doppler had a high correlation with that determined by ventriculography (r = 0.88, p less than 0.01).
Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal Women
Authors: Henry G. Bone, David Hosking, Jean-Pierre Devogelaer, Joseph R. Tucci, Ronald D. Emkey, Richard P. Tonino, Jose Adolfo Rodriguez-Portales, Robert W. Downs, Jayanti Gupta, Arthur C. Santora, Uri A. Liberman
Journal: New England Journal of Medicine (2004)

Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years.The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study.Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit.The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.
PLZF, a Tumor Suppressor Genetically Lost in Metastatic Castration-Resistant Prostate Cancer, Is a Mediator of Resistance to Androgen Deprivation Therapy
Authors: Chen-Lin Hsieh, Ginevra Botta, Shuai Gao, Tiantian Li, Eliezer M. Van Allen, Daniel J. Treacy, Changmeng Cai, Housheng Hansen He, Christopher J. Sweeney, Myles Brown, Steven P. Balk, Peter S. Nelson, Levi A. Garraway, Philip W. Kantoff
Journal: Cancer Research (2015)

Abstract Whole-exome sequencing of metastatic castration-resistant prostate cancer (mCRPC) reveals that 5% to 7% of tumors harbor promyelocytic leukemia zinc finger (PLZF) protein homozygous deletions. PLZF is a canonical androgen-regulated putative tumor suppressor gene whose expression is inhibited by androgen deprivation therapy (ADT). Here, we demonstrate that knockdown of PLZF expression promotes a CRPC and enzalutamide-resistant phenotype in prostate cancer cells. Reintroduction of PLZF expression is sufficient to reverse androgen-independent growth mediated by PLZF depletion. PLZF loss enhances CRPC tumor growth in a xenograft model. Bioinformatic analysis of the PLZF cistrome shows that PLZF negatively regulates multiple pathways, including the MAPK pathway. Accordingly, our data support an oncogenic program activated by ADT. This acquired mechanism together with the finding of genetic loss in CRPC implicates PLZF inactivation as a mechanism promoting ADT resistance and the CRPC phenotype. Cancer Res; 75(10); 1944–8. ©2015 AACR.
Preliminary observations of the effect of inhalation of PVC in man and experimental animals.
Authors: J C Wagner, N F Johnson
Journal: Environmental Health Perspectives (1981)

Attention has been focussed, both in man and experimental animals, on the effects of inhalation of the gas monomer, vinyl chloride. Recently, note is being taken of the possible effects of the inhalation of the polymer in man. The particles in question are those produced commercially as paste polymer or dispersion polymer or having an average diameter of 0.15 micrometers, and accounting for more than 10% of the production in Britain. There are now strict regulations for the control of the monomer gas, but the particles are regarded as nuisance dust and their emission is not covered by specific legislation. Our studies on rats, where both inhalation and implantation methods of exposure have been used, and examination of tissue from human cases exposed to paste polymers, indicate that these small particles can only be regarded as evidence of exposure, and on present evidence there is no indication of causation of significant pulmonary disease. Techniques have been developed by which these particles can be demonstrated in ordinary histological preparations and by transmission electron microscopy.
Was the Atrial Septal Defect Closed?-Reply
Authors: Lawrence A. Gould
Journal: JAMA (1988)

<h3>In Reply.</h3> —The physical examination of the patient revealed a normal physiological split of the second heart sound. The second heart sound did not have a fixed split. A two-dimensional echocardiogram was performed with injection of saline into a peripheral vein. There was no evidence of a right-to-left shunt from the right atrium to the left atrium. Hydrogen was not introduced during the right-sided catheterization and blood samples were not obtained to evaluate a possible step-up in the oxygen saturation.
Diet and Colorectal Adenomatous Polyps
Authors: Alfred I. Neugut
Journal: Annals of Internal Medicine (1993)

Letters15 August 1993Diet and Colorectal Adenomatous PolypsAlfred I. Neugut and Gail C. GarbowskiAlfred I. NeugutSearch for more papers by this author and Gail C. GarbowskiSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-4-199308150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Anand's comments. The time lag between the preparation of a manuscript and its publication can lead to missing a recent publication. Indeed, a new review article by our group [1] now documents seven published studies on diet and adenomatous polyps; more are undoubtedly on the way.Overall, we agree that dietary variables play a role in the incidence of adenomatous polyps, similar to that shown for colorectal cancer. We did not find an association of alcohol with adenomatous polyps after adjusting for cigarette smoking, which is related to adenoma incidence [2]. To date, however, our ...References1. Neugut AI, Jacobson JS, DeVivo I. Epidemiology of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev. 1993; 2:159-76. Google Scholar2. Lee WC, Neugut AI, Garbowski GC, et al. Cigarettes, alcohol, coffee and caffeine as risk factors for colorectal adenomatous polyps. Ann Epidemiol; (In press). Google Scholar3. Neugut AI, Garbowski GC, Lee WC, Murray T, Nieves JW, Forde KA, et al. Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps: a case–control study. Ann Intern Med. 1993; 118:91-5. Google Scholar4. Weinstein IB. Cancer prevention: recent progress and future opportunities. Cancer Res. 1991; 51(Suppl):5080s-5s. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1993Volume 119, Issue 4Page: 343KeywordsAdenomasAlcoholsCarcinogenesisColonColorectal cancerDietGenetic predispositionMedical risk factorsObservational studiesRisk management Issue Published: 15 August 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation
Authors: Yukimasa Shiotsu, Hitoshi Kiyoi, Yuichi Ishikawa, Ryohei Tanizaki, Makiko Shimizu, Hiroshi Umehara, Kenichi Ishii, Yumiko Mori, Kazutaka Ozeki, Yosuke Minami, Akihiro Abe, Hiroshi Maeda, Tadakazu Akiyama, Yutaka Kanda, Yuko Sato, Shiro Akinaga, Tomoki Naoe
Journal: Blood (2009)
Misclassification of smoking status among Southeast Asian adult immigrants.
Authors: M E Wewers, R K Dhatt, M L Moeschberger, R M Guthrie, P Kuun, M S Chen
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

A total of 1,403 Southeast Asian adult immigrant males (n = 783) and females (n = 620) from Cambodia, Laos, and Vietnam who currently resided in Central Ohio were interviewed to determine the self-reported smoking prevalence among them, and underwent biochemical confirmation of their smoking status. Variables having to do with the subjects' sociodemography, acculturation, and smoking history that were related to the misclassification of smoking status were also investigated. Self-reported current smoking rates were 40.9% and 5.6% for males and females, respectively. After verification of the subjects' smoking status by saliva cotinine assay (smoker status > or = 14 ng/ml), the rates of smoking were found to be greater, at 43.7% for males and 14.8% for females. Years of education, self-reported smoking status, country of origin, and method of healthcare payment were significant predictors of misclassification. These findings suggest that the prevalence of smoking is higher among Southeast Asian adult females than has been previously reported. Variables that predict misclassification with regard to smoking status are presented, and their implications for clinicians and researchers are discussed.
Abstract LB-16: Discovery of novel SGK1 inhibitors by a fragment-based approach: Generating patentable, chemically tractable and ligand efficient leads
Authors: Gordon Alton, Warren Wade, Laura Lingardo, Ayse Batova, Tom Smart, Chris Buhr, James W. Zapf, Peter Pallai
Journal: Cancer Research (2014)

Abstract Triple negative (ER, PR and HER2/neu negative) breast cancer (TNBC) can have an unfavorable prognosis compared to other breast cancers. TNBC is more difficult to treat since most targeted breast cancer therapies are directed at one of the three receptors. Aggressive combinatorial therapies are usually required and the cytotoxic agents used in these regimens frequently loose effectiveness with time. Serum and glucocorticoid-regulated kinase 1 (SGK1) (a serine/threonine protein kinase), promotes the growth and invasiveness of breast cancer cells. SGK1 is a key protein regulated by the glucocorticoid receptor (GR). In TNBC tumors, high expression/activity in the GR/SGK axis correlates with shorter survival times and resistance to chemotherapy. The small numbers of SGK1 inhibitors reported in the literature have resulted from screening against other kinases (such as CHK1/azaindoles) and thus are not selective and lack patentable chemical diversity. We describe the identification of novel SGK1 inhibitors using a fragment-based library screening approach. The BioBlocks Leap-To-Lead platform contains a library of novel fragment-like compounds that span a range of polarities and sizes without compromising on flexibility. For example, this 275 compound library has an average molecule weight of 160 Da; AlogP, 1.1; hydrogen bond donors, 1.1; hydrogen bond acceptors, 2.2, and rotatable bonds, 0.7 yet still contains 114 unique rings. The library was screened against fully activated human SGK1 in an ADP-Glo assay using physiologically relevant peptide substrate and an optimal ATP concentration to also identify non-classical kinase inhibitor mode binders. The fragment library was screened at 2 mM and hits were profiled in IC50 dose response. From these, several novel chemical matter hit compounds were selected that had ligand efficiency values greater than 0.3 and spanned IC50 values from 75 µM to 2000 µM. In summary, a fragment-based screening approach was used to identify several novel scaffolds that represent both classical and non-classical kinase inhibitor binding modes as hit-to-lead starting points for the optimization of novel, potent and selective SGK1 inhibitors. Citation Format: Gordon Alton, Warren Wade, Laura Lingardo, Ayse Batova, Tom Smart, Chris Buhr, James W. Zapf, Peter Pallai. Discovery of novel SGK1 inhibitors by a fragment-based approach: Generating patentable, chemically tractable and ligand efficient leads. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-16. doi:10.1158/1538-7445.AM2014-LB-16