tbuckley/cabot-search huggingface dataset:
The Oslerian Tradition
Authors: William W. Quick
Journal: JAMA (1978)

To the Editor.—  It was distressing to see the commentary The Weakening of the Oslerian Tradition, with the subtitle The Changing Emphasis in Departments of Medicine (239:317, 1978) by William Regelson, MD. It clearly specifies a viewpoint that is not shared by many internists throughout the United States.  I am a physician who is in a private practice of internal medicine and who has deliberately opted to affiliate with a university medical school with teaching on a part-time basis for the department of medicine, as well as to share other responsibilities in both private practice and patient care at state health facilities.  In South Dakota, unlike Virginia, it has become a tradition that the attending physician is the physician presented as the role model for the medical student. In South Dakota, perhaps unlike Harvard, we are completely convinced that we must train physicians for primary care medicine, and certainly internists,
Oceans and Human Health: A New Era of Environmental Opportunities
Authors: Daniel G. Baden
Journal: Environmental Health Perspectives (2005)

The National Institute of Environmental Health Sciences (NIEHS) has supported environmental health sciences that overlap with ocean science questions and resources since its inception. The second NIEHS director, David Rall, and NIEHS’s third director, Dr. Kenneth Olden, exhibited active interest in the development and funding of oceans and human health-related research, education, and outreach. The institute has provided fiscal support for regular research grants, center grants, and program project grants; for individual and institutional training grants; and for conference and meeting support. During Dr. Olden’s tenure, the institute has also demonstrated leadership in working with other institutes within the National Institutes of Health to further ocean-based biomedical research and has reached out to other funding agencies and departments of the federal government. The Marine and Freshwater Biomedical Science Center program is the longest lasting, most productive, and high-profile aspect of NIEHS’s funding in the ocean environmental health sciences, and under Dr. Olden’s leadership that program has steadily increased in stature. Developed collaboratively with Rita Colwell, immediate past director of the National Science Foundation, the present Centers for Oceans and Human Health are a joint exercise of the two agencies. The Marine and Freshwater Biomedical Science Center program, the three research foci of the present Centers for Oceans and Human Health program, and increased collaborative oceans and human health research will all contribute to the health of the world’s oceans and, by co-dependence, the health of humans. 

doi:10.1289/ehp.7964 available via http://dx.doi.org/
Is After the Reviewer.
Authors: Jas. Hendrie Lloyd
Journal: JAMA (1895)

3910Walnut St., Philadelphia, Aug. 26, 1895.  To the Editor:  —In ourJournalfor the 17th inst., appears a notice of the third volume of the Twentieth Century Practice of Medicine, in which I am charged with looseness in the manner of  in my section on the Diseases of Occupations. The charge is based, so well as I can understand it, upon the alleged fact that in quoting a passage from Patissier I did not give credit to the real author and that I ascribed sentiments to Patissier which he did not express.  The exact facts are as follows:  Patissier, a French author, in his Traite des Maladies des Artisans (Paris, 1822) page 196, writing of pastry-cooks, says that Cadet-Gassicourt said that these workmen are less debauched than bakers and more gentle and more sociable. Patissier does not include this statement from Cadet-Gassicourt in quotation marks, nor give the
Editorial: The controlled drinking controversy
Authors: V. Fox
Journal: JAMA (1976)

Alcoholism is a complex set of disorders manifested by abusive drinking. It can be the result of cultural dependency, physical addiction, or psychological dependency on the drug. By the time most people suffer enough to overcome the stigma surrounding the illness and look for help, they have some of all three dependencies at work. Writers have been describing "the alcoholisms" as a complex set of disorders with multiple etiologies for years. Serious workers in the field frequently state this fact and then proceed to write and act as if there were a single illness called alcoholism. This inconsistency has had a new upsurge lately over two major issues: (1) research aimed at establishing the possibility of controlled drinking in selected patients, and (2) abstinence as a major criterion for success in treatment. Even though we state that the label "alcoholism" is given to several disabilities, some workers become quite upset
Progestogens Used in Postmenopausal Hormone Therapy: Differences in Their Pharmacological Properties, Intracellular Actions, and Clinical Effects
Authors: Frank Z. Stanczyk, Janet P. Hapgood, Sharon Winer, Daniel R. Mishell
Journal: Endocrine Reviews (2012)

The safety of progestogens as a class has come under increased scrutiny after the publication of data from the Women's Health Initiative trial, particularly with respect to breast cancer and cardiovascular disease risk, despite the fact that only one progestogen, medroxyprogesterone acetate, was used in this study. Inconsistency in nomenclature has also caused confusion between synthetic progestogens, defined here by the term progestin, and natural progesterone. Although all progestogens by definition have progestational activity, they also have a divergent range of other properties that can translate to very different clinical effects. Endometrial protection is the primary reason for prescribing a progestogen concomitantly with postmenopausal estrogen therapy in women with a uterus, but several progestogens are known to have a range of other potentially beneficial effects, for example on the nervous and cardiovascular systems. Because women remain suspicious of the progestogen component of postmenopausal hormone therapy in the light of the Women's Health Initiative trial, practitioners should not ignore the potential benefits to their patients of some progestogens by considering them to be a single pharmacological class. There is a lack of understanding of the differences between progestins and progesterone and between individual progestins differing in their effects on the cardiovascular and nervous systems, the breast, and bone. This review elucidates the differences between the substantial number of individual progestogens employed in postmenopausal hormone therapy, including both progestins and progesterone. We conclude that these differences in chemical structure, metabolism, pharmacokinetics, affinity, potency, and efficacy via steroid receptors, intracellular action, and biological and clinical effects confirm the absence of a class effect of progestogens.
The Cell Cycle Checkpoint Gene <i>Rad9</i> Is a Novel Oncogene Activated by 11q13 Amplification and DNA Methylation in Breast Cancer
Authors: Chi Keung Cheng, Louis W.C. Chow, Wings T.Y. Loo, Tai Kwong Chan, Vivian Chan
Journal: Cancer Research (2005)

Abstract Human Rad9 (hRad9), a structural homologue of yeast Schizosaccharomyces pombe rad9, is involved in cell cycle checkpoints and apoptosis. hRad9 can serve as a corepressor of androgen receptor in prostate cancer cells, but little is known about its role in the development of breast or other cancers. In the present study, semiquantitative reverse transcription-PCR showed that Rad9 mRNA levels were up-regulated in 52.1% (25 of 48) of breast tumors, and this up-regulation correlated with tumor size (P = 0.037) and local recurrence (P = 0.033). Overexpression of Rad9 mRNA was partly due to an increase in Rad9 gene number as measured by quantitative PCR. In other breast tumors with Rad9 mRNA overexpression but without increase in gene number, there was differential methylation of two putative Sp1/3 binding sites within the first and second introns of the Rad9 gene, which was similarly found in MCF-7 breast cancer cell line with increased Rad9 mRNA. Silencing Rad9 expression by RNA interference in MCF-7 cell line inhibited its proliferation in vitro. Promoter assays indicated that the Sp1/3 site in intron 2 may act as a silencer. In vivo binding of Sp3 to intron 2 was shown by chromatin immunoprecipitation assays. Treatment of MCF-7 cell line with 5′-aza-2′-deoxycytidine reduced Rad9 mRNA expression and also increased binding of Sp3 to the demethylated intron 2 region. Collectively, these findings suggest that Rad9 is a novel oncogene candidate activated by 11q13 amplification and DNA hypermethylation in breast cancer and may play a role in tumor proliferation and local invasion.
AN UNUSUAL CASE OF NONTUBERCULOUS LUNG CAVITY RESULTING FROM HEALED LUNG ABSCESS (WITH NECROPSY REPORT)
Authors: Joseph Boch
Journal: JAMA (1927)

The medical literature abounds with reports of cases of spontaneously cured lung abscesses. The exact pathologic process in healing these abscesses is not known, as the patients recover completely and their lungs never come to inspection. A woman, aged 49, with a history of a healed lung abscess entered the National Jewish Hospital with a severe type of asthma and died ten weeks after admission. The necropsy revealed a cavity of nontuberculous character in the right upper lobe containing no inflammatory tissue. One year previous to admission, in November, 1924, she developed pneumonia, which was followed by an abscess in the right upper lung. This was drained by proper posture. After two months from the beginning of the pneumonia the drainage from the lung stopped and the abscess was pronounced, cured. Unfortunately, the asthmatic symptoms from which the patient had suffered for two and one-half years and from
Landmark perspective: Coronary atherosclerosis in soldiers. A clue to the natural history of atherosclerosis in the young
Authors: J. P. Strong
Journal: JAMA (1986)

IN THIS week's issue, the editors of<i>JAMA</i>have republished an article fromThe Journalof 33 years ago that is clearly a landmark in our understanding of the development of coronary atherosclerosis. This article, "Coronary Disease Among United States Soldiers Killed in Action in Korea," by MAJ William F. Enos, LTC Robert H. Holmes, MC, USA, and CPT James Beyer, MC, USA, documents the presence of significant coronary lesions in soldiers who were battle casualties in Korea. Those soldiers for whom age was recorded ranged from 18 to 48 years old, with an average age of 22.1 years. The article appeared at a time when mortality from coronary heart disease was reaching a zenith in the United States and being recognized worldwide as a modern epidemic. This widely cited publication dramatically showed that atherosclerotic changes appear in the coronary arteries years and decades before the age at which coronary
Abstract 1013: Angiopoietin 1/2 inhibition impairs tumor growth in an orthotopic model of renal cell carcinoma
Authors: Ashley Orillion, Kiersten Marie Miles, Li Shen, Remi Adelaiye, Eric Ciamporcero, Swathi Ramakrishnan, Sheng Yu Ku, May Elbanna, Sreenivasulu Chintala, Roberto Pili
Journal: Cancer Research (2014)

Abstract Background: Clear cell renal cell carcinoma (ccRCC), the most common form of renal cell carcinoma, is characterized VEGF driven tumor vascularization. However, in patients treated with anti-VEGF therapies inevitably tumor progression occurs, likely driven by up-regulation of alternative proangiogenic pathways including angiopoietins and c-MET. We hypothesized that angiopoietin inhibition has anti-tumor effect on RCC and may affect the development of resistance to anti-VEGF therapies. In the current study we utilized the dual angiopoietin inhibitor AMG 386 in murine models of RCC, and assessed the preclinical impact of this strategy. Methods: Seven week old female Balb/c mice were injected with 250,000 RENCA cells (luciferase expressing), one week later these mice were randomized, using bioluminescence imaging into two treatment groups: vehicle or Amgen 386 (5.6mg/kg/day, twice a week, subQ injection). Body weight measurements, tumor growth rate, and end point tumor weight measurements were used to evaluate possible side effects and the progression of RENCA tumors. Four weeks of treatment culminated in collection of tumor tissues for immunohistochemistry analysis of Ki67 and CD31. In addition we have ongoing studies utilizing patient derived xenografts (PDX) of ccRCC developed in our lab. Results: In the RENCA model AMG 386 induced a significant decrease of tumor weight by 44.0 percent (p = 0.0123). In addition, histological analysis of tumor sections revealed a high proportion of necrosis and decreased blood vessel density. Studies are ongoing with sunitinib sensitive PDXs and matched sunitinib resistant PDXs treated with AMG 386 in combination with a selective c-MET inhibitor. Results from these models will be available at the time of the meeting. Conclusions: Our preliminary results suggest that AMG 386 as a single agent is inhibiting both vascularization and tumor growth in an orthotopic renal cell carcinoma model. Ongoing studies with AMG 386 in combination with a selective c-MET inhibitor in sunitinib sensitive and resistant PDX models will provide guidance for the optimal clinical development of angiopoietin inhibitors in patients with ccRCC. Citation Format: Ashley Orillion, Kiersten Marie Miles, Li Shen, Remi Adelaiye, Eric Ciamporcero, Swathi Ramakrishnan, Sheng Yu Ku, May Elbanna, Sreenivasulu Chintala, Roberto Pili. Angiopoietin 1/2 inhibition impairs tumor growth in an orthotopic model of renal cell carcinoma. [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 1013. doi:10.1158/1538-7445.AM2014-1013
Health of the public. The academic response. Health of the Public Mission Statement Working Group
Authors: J. Showstack
Journal: JAMA (1992)

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both.
496. Stability of Oncolytic Measles Viruses during Storage and Clinical Preparation
Authors: Troy R. Wegman, Kirsten K. Langfield, Henry J. Walker, Guy E. Griesmann, Julie A. Sauer, Sharon A. Stephan, Mark J. Federspiel
Journal: Molecular Therapy (2005)

Recombinant measles viruses are being evaluated as oncolytic virotherapy agents in various pre-clinical models and a human phase I clinical trial for ovarian cancer. To support these studies, we have grown and purified measles viruses, including pre-clinical and clinical grade lots using various excipients. For clinical trials using viruses, maintenance of the agent's infectious titer is critical. Therefore, a detailed understanding of the effects of temperature and excipients on the stability of the virus during production, short-term storage, and long-term storage is required. We evaluated the biological activity of measles virus stocks by measuring the infectious titer of samples stored frozen (<-70|[deg]|C), refrigerated (1-6|[deg]|C), or diluted into normal saline at room temperature as necessary for administration to cancer patients.
Subclinical Left Ventricular Systolic Dysfunction in Patients with Severe Aortic Stenosis: A Speckle Tracking and Real Time Three Dimensional Echocardiographic Study
Authors: Betül Cengiz, Selen Yurdakul, Şükrü Taylan Şahin, Serkan Kahraman, Saide Aytekin
Journal: Journal of the American College of Cardiology (2013)
Abnormalities of Doppler Measures of Diastolic Function in the Healthy Elderly Are Not Related to Alterations of Left Atrial Pressure
Authors: Anand Prasad, Kazunobu Okazaki, Armin A. Zadeh, Erika Dijk, Qi Fu, James D. Thomas, Benjamin D. Levine
Journal: Circulation (2005)

Background— Normal healthy aging results in changes in Doppler indexes of diastolic function. One widely accepted explanation for these alterations that is based on animal data is an age-associated impairment of myocardial relaxation resulting from abnormal myocyte calcium handling. However, an alternative theory based on altered left atrial compliance with aging has been proposed in which early left atrial pressure could be low in the aged heart but rise rapidly during atrial diastole, resulting in a higher late atrial pressure and thus a normal mean pressure. We sought to explore this issue directly by performing a detailed analysis of the pulmonary capillary wedge pressure waveform obtained by right-heart catheterization during 5 different loading conditions. Methods and Results— Twelve healthy elderly sedentary subjects (mean age, 69.8±3 years) were recruited for the seniors group. An additional 12 young sedentary subjects (mean age, 35±8 years) made up the young group. All subjects were rigorously screened for comorbidities. All subjects underwent transthoracic echocardiography to determine Doppler variables of early and late transmitral filling (E and A velocities) and isovolumetric relaxation time. Each subject also underwent pulmonary artery catheterization with measurement of pulmonary capillary wedge pressure waveform during 5 different loading conditions: baseline, lower-body negative pressures of −15 and −30 mm Hg, and rapid saline infusions of 10 to 15 and 20 to 30 mL/kg. Pressure was measured at 6 points of the waveform: point 1, peak of the atrial contraction (a wave); point 2, the left atrial pressure during the start of ventricular systole; point 3, peak of atrial filling (v wave); point 4, earliest left atrial pressure during ventricular filling; and the line between points 5 and 6, pressure during diastasis. Aging resulted in a decrease in the E/A ratio ( P &lt;0.001) and a prolongation of the isovolumetric relaxation time ( P &lt;0.001) as assessed by echocardiography, but there was no effect of age on pulmonary capillary wedge pressure at any point throughout the cardiac cycle ( P =0.290). Specifically, at no measured point at any level of cardiac filling volume was the pulmonary capillary wedge pressure of the seniors lower than that of the young subjects. Conclusions— We conclude that the age-related echocardiographic change of decreasing E/A ratio is not the result of a lowering of early diastolic left atrial pressure.
Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans
Authors: Hao Wu, Isabelle Romieu, Min Shi, Dana B. Hancock, Huiling Li, Juan-Jose Sienra-Monge, Grace Y. Chiu, Hong Xu, Blanca Estela del Rio-Navarro, Stephanie J. London
Journal: Journal of Allergy and Clinical Immunology (2009)
Linkage and Microarray Analyses of Susceptibility Genes in ACI/Seg Rats: A Model for Prostate Cancers in the Aged
Authors: Satoshi Yamashita, Shugo Suzuki, Tomoko Nomoto, Yasushi Kondo, Kuniko Wakazono, Yoshimi Tsujino, Takashi Sugimura, Tomoyuki Shirai, Yukio Homma, Toshikazu Ushijima
Journal: Cancer Research (2005)

Abstract ACI/Seg (ACI) rats develop prostate cancers spontaneously with aging, similar to humans. Here, to identify genes involved in prostate cancer susceptibility, we did linkage analysis and oligonucleotide microarray analysis. Linkage analysis was done using 118 effective rats, and prostate cancer susceptibility 1 (Pcs1), whose ACI allele dominantly induced prostate cancers, was mapped on chromosome 19 [logarithm of odds (LOD) score of 5.0]. PC resistance 1 (Pcr1), whose ACI allele dominantly and paradoxically suppressed the size of prostate cancers, was mapped on chromosome 2 (LOD score of 5.0). When linkage analysis was done in 51 rats with single or no macroscopic testicular tumors, which had larger prostates and higher testosterone levels than those with bilateral testicular tumors, Pcs2 and Pcr2 were mapped on chromosomes 20 and 1, respectively. By oligonucleotide microarray analysis with 8,800 probe sets and confirmation by quantitative reverse transcription-PCR, only two genes within these four loci were found to be differentially expressed &amp;gt;1.8-fold. Membrane metalloendopeptidase (Mme), known to inhibit androgen-independent growth of prostate cancers, on Pcr1 was expressed 2.0- to 5.5-fold higher in the ACI prostate, in accordance with its paradoxical effect. Cdkn1a on Pcs2 was expressed 1.5- to 4.5-fold lower in the ACI prostate. Additionally, genes responsible for testicular tumors and unilateral renal agenesis were mapped on chromosomes 11 and 14, respectively. These results showed that prostate cancer susceptibility of ACI rats involves at least four loci, and suggested Mme and Cdkn1a as candidates for Pcr1 and Pcs2.
Prevention and Control of Hypertension by Nutritional-Hygienic Means
Authors: Jeremiah Stamler, Eduardo Farinaro, Louise M. Mojonnier, Yolanda Hall, Dorothy Moss, Rose Stamler
Journal: JAMA (1980)

In the Chicago Coronary Prevention Evaluation Program (CPEP), 115 men had definite mild hypertension at entry; another 101 men had high-normal diastolic blood pressure (BP). The nutritional-hygienic nonpharmacologic CPEP regimen achieved years-long moderate weight loss, slowing of pulse rate, and reduction in serum cholesterol levels. Sustained falls in BP were recorded—about 10/13 mm Hg for hypertensive men, resulting in long-term normalization of BP, and about 7/4 mm Hg for men with high-normal BP at entry. Change in weight and change in BP were significantly correlated. Long-term improvements in eating and exercise habits yielding moderate sustained weight loss are apparently useful in preventing high BP in hypertension-prone persons and in controlling established "mild" hypertension. (<i>JAMA</i>243:1819-1823, 1980)
Health Information on the Internet: A Study of Providers, Quality, and Users
Authors: Birte Twisselmann
Journal: BMJ (2006)

T his book—painstakingly researched and compiled over four years by an assistant professor in information management in Victoria, New Zealand—is a laudable attempt to capture thoroughly the bewildering array of global health information available on the internet and to elucidate how the internet has changed the way in which healthcare consumers and providers communicate. Inevitably, given the time it took to write, some of the information is not up to date—access to bmj.com is not universally free any more, for example.

The author argues that a paradigm shift has taken place as the …