tbuckley/cabot-search huggingface dataset:
Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Charles J. Ryan, Matthew Raymond Smith, Johann Sebastian De Bono, Arturo Molina, Christopher Logothetis, Paul L. De Souza, Karim Fizazi, Paul N. Mainwaring, Jose Maria Piulats Rodriguez, Siobhan Ng, Joan Carles, Peter Mulders, Thian San Kheoh, Thomas W. Griffin, Eric Jay Small, Howard I. Scher, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2012)

LBA4518 Background: AA is an androgen biosynthesis inhibitor that inhibits CYP17 and improves overall survival (OS) in post-docetaxel mCRPC. The primary objective of COU-AA-302 was to compare clinical benefit of AA + prednisone (P) vs placebo (PL) + P in chemo-naive, asymptomatic/mildly symptomatic mCRPC pts. Methods: 1088 pts (151 centers; 12 countries) were randomized 1:1 to AA (1 g) + P (5 mg BID) or PL + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median times estimated using K-M method including LR statistic for inference. The Lan-DeMets α-spending function was used for OS. Results:The Independent Data Monitoring Committee concluded that the OS, rPFS and secondary endpoints (Table) all favored the AA arm and unanimously recommended unblinding the study and crossing pts from PL to AA at IA (43% of total events). Median follow up = 22.2 mos. Grade 3/4 AEs (AA + P, PL + P) (%): hypertension 3.9 vs 3.0; hypokalemia 2.4 vs 1.9; ALT↑ 5.4 vs 0.7; AST↑ 3.0 vs 0.9. Conclusions:AA + P produced a statistically significant improvement in rPFS and a strong trend for increased OS at this IA. AA resulted in clinically and statistically significant effects on all secondary endpoints. IA results confirmed the acceptable tolerability/safety profile of AA. This is the first randomized trial to demonstrate both OS and rPFS benefits in chemo-naive mCRPC and that inhibition of persistent extragonadal androgen synthesis significantly delays initiation of cytotoxic chemo. While median OS (AA arm) has not been reached, median PL arm OS (27.2 mos) is the longest measured in any phase III mCRPC study. [Table: see text]
Amebic pericarditis
Authors: R. F. Heller
Journal: JAMA (1972)

Two patients with cardiac tamponade, later found to be due to amebic pericarditis, presented in the space of two months. Both patients survived the initial tamponade and were treated for amebiasis. The first patient progressed to a complete clinical cure but the second patient died, probably as a result of the development of constrictive pericarditis. Diagnosis was made in both patients on the basis of an abscess in the left lobe of the liver (confirmed by liver scan and surgery), the presence of brown, sterile pus in both the liver abscess and pericardium, and high titers of amebic hemagglutinating antibodies in the blood. One of the patients is a native American who had not left Chicago for 30 years. She is thought to represent the first case of amebic pericarditis arising in the United States.
The Role of Structure in the Disposition of Halogenated Aromatic Xenobiotics
Authors: Linda S. Birnbaum
Journal: Environmental Health Perspectives (1985)

Halogenated aromatic xenobiotics such as the chlorinated and brominated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans are widespread environmental contaminants. The number, position, and nature of the halogen atoms as well as the structure of the aromatic rings influence the disposition of these chemicals in living systems. Absorption is governed primarily by the physical properties of lipophilicity and solubility. Distribution through the blood occurs by nonspecific binding to plasma proteins and cellular components. Liver and adipose tissue are the major depots. Metabolism is a prerequisite for excretion. The highly substituted isomers tend to be resistant to metabolism. The route of excretion shifts from urine to feces with increasing size and number of halogen atoms. Although pharmacokinetic modeling has allowed some predictions to be made from one compound to another or across species, more information on metabolism is required in order to improve the ability to predict the disposition in humans of this class of toxic environmental pollutants.
Table of Contents
Authors: Norman Hollenberg, Erik Van Bommel, Yuliya Lytvyn, Bruce Perkins, Nima Soleymanlou, Nora Fagan, Audrey Koitka-Weber, Jaap Joles, David Cherney, Daniël Van Raalte, Volker Haase, Willi Jahnen-Dechent, Edward Smith, Yi Wen, Steven Crowley, Sebastiaan Heidt, Frans Claas, Kisha Sivanathan, P Coates, David Pinelli, Anat Tambur, Germaine Wong, Vimal Derebail, Michelle Rheault, Bryce Kerlin, Nicolas Garcelon, Anita Burgun, Rémi Salomon, Antoine Neuraz, Marie Ito, Tetsuhiro Tanaka, Taisuke Ishii, Takeshi Wakashima, Kenji Fukui, Masaomi Nangaku, Ken-Ichi Akiyama, Yutaka Miura, Hirosaka Hayashi, Asuka Sakata, Yoshitaka Matsumura, Masaki Kojima, Ken Tsuchiya, Kazuhiro Nitta, Hiroshi Shiizaki, Makoto Kurosu, Taisuke Furusho, Eisei Sohara, Shintaro Mandai, Hiroaki Kikuchi, Naohiro Takahashi, Takuya Fujimaru, Hiroko Hashimoto, Yohei Arai, Fumiaki Ando, Moko Zeniya, Takayasu Mori, Koichiro Susa, Kiyoshi Isobe, Naohiro Nomura, Kohei Yamamoto, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Hiroaki Motohashi, Yu Tahara, Daniel Whittaker, Huei-Bin Wang, Takahiro Yamaji, Hiromichi Wakui, Atsushi Haraguchi, Mayu Yamazaki, Hiroki Miyakawa, Koki Hama, Hiroyuki Sasaki, Tomoko Sakai, Rina Hirooka, Kengo Takahashi, Miku Takizawa, Saneyuki Makino, Shinya Aoyama, Christopher Colwell, Shigenobu Shibata, Daniela Hermert, Ina Martin, Lucy Reiss, Xiyang Liu, Daniel Breitkopf, Katharina Reimer, Christina Alidousty, Thomas Rauen, Jürgen Floege, Tammo Ostendorf, Ralf Weiskirchen, Ute Raffetseder
Journal: Kidney International (2020)
WISCONSIN'S MEDICAL LAW IN OPERATION.
Journal: JAMA (1907)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Preventive Medicine
Authors: Suzanne Dandoy
Journal: JAMA (1990)

Several significant developments during the past 18 months will enhance the ability of all physicians to offer preventive medical services in their practices. In early 1989, the work of the US Preventive Services Task Force was presented to the Department of Health and Human Services and then published as the<i>Guide to Clinical Preventive Services</i>.<sup>1</sup>For 4 years, a team of 20 experts from medicine and related fields evaluated 169 interventions to prevent 60 different illnesses and conditions. The task force used rigorous scientific criteria in reviewing the evidence (included in the guide) for and against each process. The resulting recommendations include screening for early detection, immunization, and chemoprophylaxis, as appropriate, for vascular diseases, cancer, metabolic disorders, infectious diseases, hematologic and ophthalmologic disorders, prenatal conditions, mental disorders, and substance abuse. In addition, the effectiveness of counseling to prevent tobacco use, improve exercise and nutrition practices, prevent injuries and dental
PERMANGANATE OF POTASSIUM AS AN ANTIDOTE TO MORPHIN.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NMR Spectroscopy of Brain Metabolism In Vivo
Authors: J. Prichard
Journal: Annual Review of Neuroscience (1986)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Laetrile for cancer
Authors: T. H. Jukes
Journal: JAMA (1976)

ANOTHER chapter is being written in the melancholy history of cancer quackery. This chapter, entitled "Laetrile," follows the outline of its predecessors. First, a remedy is introduced resulting from a novel "strange idea." Next, its promoters become so dedicated to advocating the remedy that they cannot retreat from a position which becomes untenable as a result of exposure of the worthlessness of the remedy. Third, the promoters are reinforced in their fraudulence by champions of the "underdog" against the "establishment," and by the surviving relatives of the deceased victims of cancer. These relatives, because of feelings of guilt, cling to their belief that treatment with the "remedy" was the best possible therapy. Finally, vast sums of money and amounts of time are wasted on elaborate tests of the "remedy" by qualified scientists who should be doing something useful. These tests are usually undertaken because of coercion by legislators and other
Foodborne disease outbreaks in nursing homes, 1975 through 1987
Authors: W. C. Levine
Journal: JAMA (1991)

<h3>Objective.</h3> —To describe the epidemiology of foodborne disease outbreaks in nursing homes and to identify where preventive efforts might be focused. <h3>Data Sources.</h3> —Reports by state and local health departments of foodborne disease outbreaks occurring from January 1,1975, through December 31, 1987. <h3>Study Selection.</h3> —Foodborne disease outbreaks reported to the Centers for Disease Control, Atlanta, Ga, on standard investigation forms. <h3>Data Extraction.</h3> —Each foodborne disease outbreak report was examined by an epidemiologist or statistician. Outbreaks were considered to have a known pathogen if confirmed by laboratory tests, and a known vehicle when an epidemiologic investigation implicated a specific food item. <h3>Data Synthesis.</h3> —From 1975 through 1987, 26 states reported 115 outbreaks of foodborne disease in nursing homes, causing illness in 4944 persons and death in 51. These outbreaks represented 2% of all reported foodborne disease outbreaks and 19% of outbreak-associated deaths in this period. Of 52 outbreaks with a known cause,<i>Salmonella</i>was the most frequently reported pathogen, accounting for 52% of outbreaks and 81% of deaths.<i>Salmonella enteritidis</i>outbreaks accounted for 56% of the<i>Salmonella</i>-associated deaths since 1981. The implicated food vehicles in<i>S enteritidis</i>outbreaks were made with eggs or prepared with equipment contaminated with eggs. Staphylococcal foodborne disease was the next most commonly identified cause, accounting for 23% of outbreaks. <h3>Conclusions.</h3> —Since the elderly are at high risk for serious morbidity from foodborne disease, nursing homes should practice careful food handling, preparation, and storage procedures; provide education for food handlers; and have active infection control programs to rapidly detect and control outbreaks of foodborne disease. (<i>JAMA</i>. 1991;266:2105-2109)
Corrections
Journal: Hepatology (2004)

Diagnosis, management, and treatment of hepatitis C" the following corrections should be noted:In Table 4, the upper dynamic range limit of the quantitative assay is incorrectly expressed in the third row.The table is correct as listed below:On page 1149 of the article under the heading Qualitative Assays, the paragraph should appear as follows:HCV RNA can be detected in blood using amplification techniques such as polymerase chain reaction (PCR) or transcription-mediated amplification (TMA). 28The Food and Drug Administration (FDA) has approved 2 PCRbased tests for qualitative detection of HCV RNA; (1) Amplicor Hepatitis C Virus Test, version 2.0, and (2) Cobas Amplicor Hepatitis C Virus Test, version 2.0 (Roche Molecular Systems, Branchburg, NJ), which have limits of detection of approximately 50 IU/mL.A third approved test is the VERSANT ® HCV RNA Qualitative Assay (Bayer Diagnostics, Tarrytown, NY) which employs the TMA technology and has a sensitivity limit of 9.6 IU/mL.Other commercially available non-approved assays are used by some diagnostic laboratories.In the June issue, Volume 39, Issue 6, pages 1623-1630, "Sustained rise of portal pressure after sclerotherapy, but not band ligation, in acute variceal bleeding in cirrhosis" by Avgerinos et al., in the Abstract the words 'rebleeding (p ϭ .05)and' were incorrect.The sentence should read as:Patients with an initial HVPG greater than 16 mm Hg had, despite endoscopic treatment, a significantly higher likelihood of death (P ϭ .024)and overall failure (P ϭ .037).
TARGETING THE 19S PROTEASOMAL SUBUNIT, RPT4, IN COLON CANCER CELLS INDUCES CELL DEATH AND REDUCES CELLULAR PROLIFERATION IN VITRO AND IN VIVO
Authors: K Boland, N McCawley, D Ryan, S Hector, E Kay, D McNamara, F Murray, C G Concannon, J H M Prehn
Journal: Gut (2013)

<h3>Introduction</h3> Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the US with half a million deaths worldwide. In recent years much research has centered on the ubiquitin-proteasome pathway (UPP), responsible for the degradation of the majority of intracellular proteins, as a therapeutic target for cancer treatment, with deregulation of the UPP frequently observed in a number of malignancies. Indeed, malignant cells have higher vulnerability to the cytotoxic effects of proteasomal inhibition through their greater dependence on proliferative and anti-apoptotic pathways. <h3>Aims/Background</h3> Here we investigated the expression of the 19S proteasome subunit, Rpt4, one of six ATPases of the 19S regulatory subunit involved in the recognition of proteasome substrates and their unfolding and entry into the catalytic core, in tumour samples derived from patients with CRC. <h3>Results</h3> Western blotting and immunohistochemical staining of tissue microarrays demonstrated increased expression of Rpt4 in tumour tissue compared to patient matched normal mucosa. Inhibition of Rpt4 expression using siRNA in HCT-116 colorectal cancer cells showed that inhibition of Rpt4 expression leads to reduced cellular proliferation, increased apoptosis and reduced clonogenic survivalin a p53 independent manner. CRL 1807 non-transformed colonocytes remained largely unaffected suggesting that tumour cells may be selectively sensitive to Rpt4 inhibition. Moreover, chemotherapy resistant cell lines were demonstrated to be sensitive to the effects of Rpt4 inhibition. In addition Rpt4 inhibition acted in concert with 5-FU based chemotherapeutic agents by enhancing levels of induced cell death. Interestingly, Rpt4 inhibition led to decreased proteolytic activity of the proteasome. Finally, we could demonstrate that decreased Rpt4 expression could inhibit tumour growth in vivo. HCT-116 luc2 ULTRA (Caliper LS) colorectal cancer cells transfected ex vivo with Rpt4 siRNA and subcutaneously implanted in Balb/c nu-nu immunodeficient mice had significantly increased survival compared to controls. In the same tumour model a cell penetrating peptide based microparticle delivery system administering Rpt4 siRNA via intratumoural injection, demonstrated that in vivo gene silencing of Rpt4 using 0.1 mg/kg siRNA led to reduced tumour volume growth and statistically significant improvement (Log-rank Mantel Cox Test) in survival in these mice. <h3>Conclusion</h3> Taken together our data suggest the specific inhibition of Rpt4 function may represent a novel therapeutic target for the treatment of CRC.
Donor-derived chimerism in recipients of organ transplants
Authors: R Steinman
Journal: Hepatology (1993)

The current issue of HEPATOLOGY features an article on "Cell Migration and Chimerism After Whole-organ Transplants" by Starzl et al. (1) at the University of Pittsburgh Health Science Center.This article, while overwhelming in its length and number of figures, brings together and adds to a flurry of recent reports in which this group has uncovered a new and potentially significant form of cell migration from organ grafts.Cells of donor (graft) origin widely populate the tissues of the recipient, resulting in a state of chimerism.This phenomenon was first noted after liver transplantation but also is apparent with grafts of intestine, lung, kidney and heart.Cell migration and chimerism of the reverse sort (i.e., a movement from recipient to the graft) is not new.Recipient bone marrow-derived WBCs, particularly macrophages and dendritic cells, can repopulate the corresponding cellular compartments in any donor organ.What Starzl et al. have uncovered is a flux from donor to recipient.As they put it, all donor organs are to some extent "mini-marrows" and able to seed many recipient organs with donor-derived cells.The donorderived cells likely are white cells and may include specialized antigen-presenting dendritic cells (2).We will summarize briefly the findings of Starzl et al., relating these to other instances of cell migration from donor to recipient.We will consider a possible mechanism for the phenomenon of long-term, donor-based chimerism and discuss the important consequences of chimerism that are proposed by the authors.There are three, which are as follows: (a) donor-derived cells influence the host's immune system and allow grafts to be accepted long term with reduced immunosuppression; (b) donor-derived cells can alleviate certain metabolic deficiencies such as type IV glycogen storage and Gaucher's diseases; and (c) implicitly, improved methods for treating transplant recipients and certain genetic deficiencies may be obtained by defining and enhancing donor-derived chimerism.We suspect that most readers of HEPATOLOGY will agree that these three consequences of chimerism still lie in the realm of hypothesis.Yet the data are new and provocative.Interestingly,
Reply
Authors: M. Eric Gershwin, Ian R. Mackay
Journal: Hepatology (2008)

2-octynoic acid-coupled bovine serum albumin in complete Freund's adjuvant (CFA) containing a high concentration (10 mg/mL) of Mycobacterium tuberculosis.In several earlier reports, our group has described the use of a similar route and "boosted" CFA formulation to sensitize a range of mouse strains (including C57BL/6 and SJL/J) with components of PDC. 1,[5]6][7] This universally results in the formation of autoantibodies.However, inflammatory portal tract lesions are only observed reproducibly in SJL/J mice, with a smaller response observed in the portal tract of some C57BL/6 animals.In our experience, the capacity to break T cell tolerance to self-PDC, critical for the induction of liver histological change, is similarly restricted to SJL/J 6 and C57BL/6 mice (Fig. 1).Importantly, our group's established observation that control sensitization fails to induce significant portal tract inflammation in any of the mouse strains we tested is entirely consistent with the data presented by Wakabayashi et al. 4 In 2002, Gershwin's group published two similar reports which were wholly critical of the animal model developed and used by our group. 8,9 Specifically, these reports claimed that intraperitoneal sensitization with boosted CFA (or even incomplete Freund's adjuvant) led to antigen nonspecific portal tract inflammation, with the inference that mouse sensitization approaches of this type are invalid for modeling primary biliary cirrhosis.Our group disagreed strongly with these findings and has successfully continued to use the intraperitoneal route with boosted CFA 6,10 or specific toll-like receptor ligands 7 to break self-tolerance of PDC in SJL/J mice, leading to the development of specific portal tract inflammatory changes. 1,6,7,10 We are now pleased to note that Gershwin's group has successfully extended our intraperitoneal sensitization procedure, and thereby validated our broad approach, by using intraperitoneal antigen in boosted CFA to produce mild but specific portal tract inflammation in C57/BL6 mice. 4 Their finding of no significant portal tract inflammation in control animals sensitized with boosted CFA and unmodified bovine serum albumin supports our view that the portal tract changes seen in animals induced to break immune tolerance to self-PDC using this sensitization approach are indeed a disease-specific phenomenon, supporting the validity of both our and their postulated murine models.Our experience using this system to sensitize with biotin-modified proteins 10 and our studies comparing responses in different mouse strains lead us to suggest that sensitization of SJL/J mice with octynoic acid-modified proteins in boosted CFA might induce an even greater specific inflammatory response within the portal tract.