tbuckley/cabot-search huggingface dataset:
Abstract 4509: Genetically encoded chimeric polypeptide nanoparticles for paclitaxel delivery to triple negative breast cancer.
Authors: Jayanta Bhattacharyya, Jonathan McDaniel, Ashutosh Chilkoti
Journal: Cancer Research (2013)

Abstract Triple negative breast cancer (TNBC) represents an important clinical challenge, because TNBC, like other breast cancer subtypes is highly metastatic, but TNBC displays a shorter median time to relapse and death. Chemotherapy remains the mainstay of treatment of TNBC, as it gives a markedly higher response rate than endocrine therapy or other available targeted agents. Current treatment strategies for TNBC include treatment with anthracyclines, taxanes, and platinates. Like other drugs, paclitaxel shows a lack of selectivity towards tumor cells, sub-optimal pharmacokinetics and bio-distribution, leading to limited efficacy and significant systemic toxicity. Although AbraxaneTM (albumin bound paclitaxel) an improved formulation of paclitaxel compared to the original chremophor formulation has been used to treat TNBC, it also suffers from systemic toxicity such as sensory neuropathy, neutropenia, nausea, and anemia. In an effort to overcome the limited efficacy and systemic toxicity of current paclitaxel formulations, we have designed a novel polypeptide drug delivery system where paclitaxel is covalently attached to a genetically engineered chimeric polypeptide (CP) through a pH sensitive linker such that covalent conjugation of multiple copies of Paclitaxel at one end of the CP spontaneously triggers the self-assembly of the drug-CP conjugate into sub 100 nm size nanoparticles that are ideal for targeting solid tumors through the enhanced permeability and retention (EPR) effect.We found that in a human triple negative breast cancer cell (MDA-MB-231), the CP-paclitaxel conjugate showed substantial cytotoxicity that was similar to free drug. CP-Paclitaxel nanoparticle treated mice with orthotopic MDA-MB-231 tumors showed significantly greater tumor regression as well as enhanced overall survival compared to free drug. These results are promising because they demonstrate the potential of rationally engineered nanoparticle drug carriers to greatly improve the efficacy of currently approved cytotoxic agents for the treatment of solid tumors. In future work, we will evaluate the efficacy of CP-Paclitaxel nanoparticles combined with a tyrosine kinase inhibitor that mimics current combination chemotherapy. Citation Format: Jayanta Bhattacharyya, Jonathan McDaniel, Ashutosh Chilkoti. Genetically encoded chimeric polypeptide nanoparticles for paclitaxel delivery to triple negative breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4509. doi:10.1158/1538-7445.AM2013-4509
Hormone treatment plus radiation delays growth of prostate cancer
Authors: Janice Hopkins Tanne
Journal: BMJ (2008)

Four months of androgen deprivation combined with external beam radiation slowed growth of prostate cancer—especially bone metastases—by up to eight years, according to a long term study from the University of California in San Francisco and collaborating sites ( Journal of Clinical Oncology 2008 Jan 2 doi: 10.1200/JCO.2007.13.9881).

The study, which began in 1987, evaluated 456 men at high risk, with a median age of 70. They had large prostate tumours (5 by 5 cm), and many had high Gleason scores (7-10) indicating that cells were higher grade and usually more aggressive, and high concentrations …
POSTCILIARY SCLERAL TREPHINING FOR ACUTE GLAUCOMA
Authors: A. E. EWING
Journal: JAMA (1918)

As the several procedures in the case reported below have resulted in a blind eye, the material is offered only as a study in the intricate problem of glaucoma.  REPORT OF CASE  A healthy unmarried woman, aged 57, during the course of a stye two weeks before I saw her, noticed that her right pupil was large and that the vision was not so good as formerly. Since then she had been using physostigmin (eserin), prescribed by a physician, without relief.  July 18, 1917, in the left eye the tension as determined by the Schiotz tonometer was 20, and the vision 20/20 with correction 1.75 spheric. There was a large, old retinochoroidal atrophic spot in the lower nasal portion of the fundus. The field was normal. In the right eye the tension with the Schiotz tonometer was 57, and the vision 8/150. The cornea was steamy over the central portion.
Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus
Authors: Robert R Graham, Chris Cotsapas, Leela Davies, Rachel Hackett, Christopher J Lessard, Joanlise M Leon, Noel P Burtt, Candace Guiducci, Melissa Parkin, Casey Gates, Robert M Plenge, Timothy W Behrens, Joan E Wither, John D Rioux, Paul R Fortin, Deborah Cunninghame Graham, Andrew K Wong, Timothy J Vyse, Mark J Daly, David Altshuler, Kathy L Moser, Patrick M Gaffney
Journal: Nature Genetics (2008)
Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury
Authors: C. Roger White, Jonathan Shelton, Shi-Juan Chen, Victor Darley-Usmar, Leslie Allen, Cheryl Nabors, Paul W. Sanders, Yiu-Fai Chen, Suzanne Oparil
Journal: Circulation (1997)

Background It has been suggested that reendothelialization of damaged blood vessels protects against the vascular injury response. The goal of the present study was to determine whether estrogen restores endothelial cell function in balloon-injured rat carotid arteries. Methods and Results Ten-week-old male and female Sprague-Dawley rats with intact gonads underwent balloon injury to the right common carotid artery. Female rats were randomized to receive either daily subcutaneous injections of 17β-estradiol (17β-E 2 ; 20 μg · kg −1 · d −1 ) or vehicle over the course of the study. Vessel morphology was assessed 2 weeks after injury. Significant neointima formation was observed in vehicle-treated males. This response was blunted in vehicle-treated and 17β-E 2 –supplemented females. Intima-to-media ratios were 1.28±0.23 (males), 0.72±0.07 (vehicle-treated females), and 0.49±0.07 (17β-E 2 –supplemented females). To test whether reductions in neointimal lesion formation were related to the functional reendothelialization of the damaged vessel, endothelium-dependent relaxation was tested in isolated ring segments from the three experimental groups. Vessels were precontracted with phenylephrine followed by cumulative administration of acetylcholine, an endothelium-dependent vasodilator. Maximum relaxation to acetylcholine was 8.13±1.70% (males), 22.06±4.36% (vehicle-treated females), and 46.47±3.48% (17β-E 2 –supplemented females). The enhanced endothelium-dependent relaxation of rings from 17β-E 2 –supplemented females correlated with reduced neointimal proliferation in this group. The concentration of nitric oxide metabolites in plasma correlated positively with plasma 17β-E 2 concentration. Conclusions These results suggest that estrogen protects against neointimal injury in the balloon-injured rat, at least in part, by facilitating the reendothelialization of the damaged vessel.
Erlotinib Versus Gefitinib for Control of Leptomeningeal Carcinomatosis in Non–Small-Cell Lung Cancer
Authors: Eunyoung Lee, Bhumsuk Keam, Dong-Wan Kim, Tae Min Kim, Se-Hoon Lee, Doo Hyun Chung, Dae Seog Heo
Journal: Journal of Thoracic Oncology (2013)
Treadmill exercise promotes cyclic alterations in coronary blood flow in dogs with coronary artery stenoses and endothelial injury.
Authors: J F Eidt, J Ashton, P Golino, J McNatt, L M Buja, J T Willerson
Journal: Journal of Clinical Investigation (1989)

We have previously shown in anesthetized, open-chest dogs with coronary stenosis and endothelial injury that serotonin and/or thromboxane A2 (TXA2) receptor activation play a major role in the mediation of platelet-dependent, intermittent coronary occlusion. Using a similar model in awake, closed-chest dogs, we tested the following hypotheses: (a) treadmill exercise promotes the development of cyclic flow variations in dogs with coronary stenoses and endothelial injury; (b) ventricular pacing does not induce cyclic flow variations in the same dogs; and (c) TXA2 and/or serotonin are important mediators of exercise-induced cyclic flow variations in this model. The surgical preparation consisted of the application of a hard, flow-limiting constrictor and a Doppler ultrasonic flow probe around the left coronary artery of 11 dogs. Treadmill exercise resulted in the prompt development of cyclic flow variations in all 11 dogs. Ventricular pacing at rates as high as 170 beats/min induced cyclic flow variations in only one of five dogs. Exercise-induced cyclic flow variations were abolished by TXA2 and/or serotonin receptor antagonists in all but one dog. Thus, (a) treadmill exercise promotes the development of cyclic flow variations in dogs with coronary stenoses and endothelial injury; (b) ventricular pacing does not induce cyclic flow variations in most dogs in the same model; and (c) TXA2 and/or serotonin are important mediators of cyclic flow variations in this model.
Request for Complementary Medicine After Brain Death
Authors: Erwin J. O. Kompanje
Journal: JAMA (2008)

2008;247(3):597-601. 2. Habbema JD, Tan SY, Cronin KA. Impact of mammography on US breast cancer mortality, 1975-2000: are intermediate outcome measures informative? J Natl Cancer Inst Monogr. 2006;(36):105-111. 3. Duffy SW, Agbaje O, Tabar L, et al. Overdiagnosis and overtreatment of breast cancer: estimates of overdiagnosis from two trials of mammographic screening for breast cancer. Breast Cancer Res. 2005;7(6):258-265. 4. Ganott MA, Sumkin JH, King JL, et al. Screening mammography: do women prefer a higher recall rate given the possibility of earlier detection of cancer? Radiology. 2006;238(3):793-800. 5. Berry DA, Cronin KA, Plevritis SK, et al; Cancer Intervention and Surveillance Modeling Network (CISNET) Collaborators. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353(17):1784-1792.
Leopold's Principles and Methods of Physical Diagnosis
Authors: Alvan R. Feinstein
Journal: JAMA (1965)

Clinical Examination: A Textbook for Students and Doctors.  By Teachers of the Edinburgh Medical School. Edited by John Macleod. 513 pp, 70 illus. $7. Williams & Wilkins Co., 428 E Preston St, Baltimore 21202, 1964  Two more textbooks indicate the persisting importance of the clinician's role as an observer of sick people. Leopold's book is the more conventional. After the customary obeisance to history-taking, its chapters present the techniques of physical examination for each region of the body, followed by accounts of normal findings, abnormalities, and interpretations. The text is handsomely published, wellillustrated, and—in Dr. Hopkins' thorough revision—has a distinctly contemporary flavor sometimes lacking in comparable books that have gone through multiple editions.  A drawback common to many other books on physical diagnosis is the frequent use of inverse clinical logic. Instead of cataloging the pathologic entities that produce such manifestations as thoracic dullness or diastolic murmurs, the book describes
Foregoing Life-Sustaining Treatment
Authors: ELI J. KLEINMAN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 August 1986Foregoing Life-Sustaining TreatmentELI J. KLEINMAN, M.D.ELI J. KLEINMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-2-307_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The patient described as "hopelessly injured" by Braithwaite and Thomasma in their proposed anti-cruelty policy (1) does not, I believe, meet even their own stated criteria for the designation. Although the authors approached the task of establishing a new set of guidelines by attempting to avoid past pitfalls, they have stumbled and substituted their own set of quality-of-life judgments for the generalizations and assumed truisms that have made previous efforts fall short of their noble purpose. I submit that the initial definition of "hopeless injury" is flawed and that the premise that "life and health should be...Reference1. BRAITHWAITETHOMASMA SC. New guidelines on foregoing life-sustaining treatment in incompetent patients: an anti-cruelty policy. Ann Intern Med. 1986;104:711-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 3671 Hudson Manor Terrace; Riverdale, NY 10463 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1986Volume 105, Issue 2Page: 307-307KeywordsFalls Issue Published: 1 August 1986 PDF DownloadLoading ...
Epidemiologic Basis of Tuberculosis Eradication
Authors: WILLIAM W. STEAD
Journal: Annals of Internal Medicine (1970)

Editorial Notes1 July 1970Epidemiologic Basis of Tuberculosis EradicationWILLIAM W. STEAD, M.D., F.A.C.P.WILLIAM W. STEAD, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-73-1-135 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThat tuberculosis is on the wane in industrialized countries is well known to all. But like any self-respecting enemy, tuberculosis does not capitulate abruptly but retreats into enclaves in which it is able to persist. Tubercle bacilli remain alive but dormant in apparently healthy persons and may erupt into clinical disease at any time that defenses fail. In order to press the enemy further at this stage of the battle it is necessary to understand its behavior as completely as possible. Foremost among studies clarifying the behavior of tuberculosis in retreat has been the Danish Tuberculosis Index; a recent report,...References1. HORWITZWILBEKERICKSON OEP: Epidemiological basis of tuberculosis eradication. 10. Longitudinal studies of the risk of tuberculosis in the general population of a low-prevalence area. Bull WHO 41:95-113, 1969 MedlineGoogle Scholar2. STEAD W: Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: recrudescence of residuals of the primary infection or exogenous reinfection? Amer Rev Resp Dis 95:729-745, 1967 MedlineGoogle Scholar3. STEAD W: Pathogenesis of the sporadic case of tuberculosis. New Eng J Med 277:1008-1012, 1967 CrossrefMedlineGoogle Scholar4. STEADKERBYSCHLUETER WGD: The clinical spectrum of primary tuberculosis in adults. Ann Intern Med 68:731-745, 1968 LinkGoogle Scholar5. STEAD W: The new face of tuberculosis. Hospital Practice 4:62-68, 1969 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Marquette School of Medicine Milwaukee County General Hospital Milwaukee, Wis. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrug Delivery in Respiratory Diseases: Current Opportunities, Molecular and Cellular Mechanism, and Future ChallengesChasing END TB 2025: Arithmetic needed for logistics! 1 July 1970Volume 73, Issue 1Page: 135-136KeywordsBehaviorEpidemiology Issue Published: 1 July 1970 PDF downloadLoading ...
Presence and formation of cobalamin analogues in multivitamin-mineral pills.
Authors: H Kondo, M J Binder, J F Kolhouse, W R Smythe, E R Podell, R H Allen
Journal: Journal of Clinical Investigation (1982)

Because the origin of cobalamin (vitamin B12) analogues in animal chows and animal and human blood and tissues is unknown, we investigated the possibility that multivitamin interactions might convert cobalamin to cobalamin analogues. We homogenized three popular multivitamin-mineral pills in water, incubated them at 37 degrees C for 2 h, and isolated the cobalamin. Using paper chromatography we observed that 20-90% of the cobalamin was present as cobalamin analogues. Studies using CN-[57Co]cobalamin showed that these analogues were formed due to the concerted action of vitamin C, thiamine, and copper on CN-cobalamin. These cobalamin analogues are absorbed from the gastrointestinal tract of mice and either fail to stimulate or actually inhibit cobalamin-dependent enzymes when injected parenterally. We conclude that CN-cobalamin can be converted to potentially harmful cobalamin analogues by multivitamin-mineral interactions and that these interactions may be responsible for the presence of cobalamin analogues in animal chows and animal and human blood and tissues.
RESPONSE TO THE TOAST, "EPHRAIM McDOWELL."
Authors: JOSEPH EASTMAN
Journal: JAMA (1895)

In a hallowed spot, a typical American home, in Rockbridge Co., Va., Nov. 11, 1771, a male child was born. It has been said that  men, like great mountains, stand alone, with the valley of ancestry on the one side and the gulf of posterity on the other. This towering character, however, did not stand alone, for the foot-hills of his ancestry were of decided magnitude, prophetic of a genius destined to become one of the greatest benefactors of the human race. His ancestry for three generations commingled the best Scotch and Irish blood, coursing the arteries of men and women of strong bodies and strong characters—characters emphasized, energized and vitalized on historic battle-fields with red-skins, red-coats, wild beasts and hardships of the primitive Virginia forests.  Figuratively speaking, this child was number nine in a family of eleven children. When 13 years of age his parents moved to Danville,
Reliability of Stress Thallium-201 Scanning in the Clinical Evaluation of Coronary Artery Disease
Authors: JERRY STOLZENBERG, ROSE LONDON
Journal: Clinical Nuclear Medicine (1979)

Stress thallium-201 scanning proved to be a highly sensitive and specific screening procedure for myocardial ischemia in 52 consecutive cases with coronary arteriograms. Stress thallium-201 scanning was considerably more accurate and more specific than the exercise electrocardiogram (ECG) as evidenced by a sensitivity of 83% compared to 55%, and a specificity of 94% compared to 82%. When submaximal stress tests were excluded, improved sensitivity of thallium scan to exercise ECG was 95% to 64% with no change in specificity. Factors producing negative thallium scans in the presence of coronary artery disease were: delay in obtaining the first post-exercise scan, positioning and observing variability, severe three-vessel disease uniformly affecting all myocardial segments, and failure to achieve maximal stress testing due to attenuation of the heart-rate response by propranolol or somatic complaints.
Regional Distribution of Pulmonary Arterial Blood Flow in Acute Asthma
Authors: Fred S. Mishkin
Journal: JAMA (1968)

In 19 adult patients, during an acute asthmatic attack, the regional distribution of pulmonary arterial blood flow was measured by means of radioisotope lung scanning after the intravenous injection of iodinated I 131 serum albumin aggregated. All but one patient had focal perfusion abnormalities. In two of six patients examined during a repeat attack, the abnormalities appeared to be localized in the same regions, while in three other patients, different areas of the pulmonary circulation were affected. In the remaining patient, scans were normal during the two consecutive acute asthmatic attacks. In all six patients studied during remission, the scan pattern returned towards normal. These findings are of importance in the differential diagnosis of acute bronchial asthma, chronic obstructive emphysema, and pulmonary embolism.
Acceptability of human risk.
Authors: R E Kasperson
Journal: Environmental Health Perspectives (1983)

This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility.
Silent Victims — An Epidemic of Childhood Exposure to Domestic Violence
Authors: Megan Bair-Merritt, Barry Zuckerman, Marilyn Augustyn, Peter F. Cronholm
Journal: New England Journal of Medicine (2013)

More than 15 million U.S. children live in families affected by intimate partner violence; about 7 million witness severe violence, such as the assault of one parent by another. Exposure to such violence has been linked to higher rates of physical health problems.
The prospective role of abnormal methyl metabolism in cadmium toxicity.
Authors: Lionel A Poirier, Tatyana I Vlasova
Journal: Environmental Health Perspectives (2002)

Several lines of evidence point to the probable role of abnormal methylation processes in the toxicology of metals and other xenobiotics. The spectrum of toxic effects exhibited by such metals as Ni, As, and Cd, as well as by Zn deficiency, often resemble those seen in animals chronically fed methyl-deficient diets. These metal-associated pathologies include cancer, atherosclerosis, birth defects, neurological disturbances, and pancreatic lesions. In addition, each of the above agents has been shown to alter normal methyl group metabolism in vivo or in vitro. In the present studies, we compared the effects on the enzyme DNA methyltransferase (MTase) of two metal ions: the essential metal Zn and the carcinogen Cd. MTase extracts were obtained from the hepatic nuclei of rats fed a methyl-deficient diet (lacking choline and folate) for 7 and 24 weeks. Control animals were fed the same diet supplemented with each of these vitamins. Zn and Cd both inhibited MTase in the nuclear extracts from both the control and the methyl-deficient rats. The inhibitory activity of Cd was greater than that of Zn regardless of whether the nuclear extracts were from the control or the deficient animals. In addition, the kinetics of Cd inhibition of MTase activity were different in the nuclear extracts from the control and methyl-deficient rats. The results provide evidence that the carcinogenic effects of Cd may be mediated in part through abnormal DNA methylation.