tbuckley/cabot-search huggingface dataset:
Androgen Deprivation in Prostate Cancer — Step by Step
Authors: Peter Albertsen
Journal: New England Journal of Medicine (2009)

Clinicians and researchers have debated the relative efficacy and timing of androgen deprivation since 1941, when Charles B. Huggins and Clarence V. Hodges reported that androgen deprivation reduced testosterone levels and produced dramatic positive therapeutic responses in patients with advanced prostate cancer.1 By 1966, when Huggins won the Nobel Prize in Physiology or Medicine for this work, many clinicians assumed that castration or treatment with diethylstilbestrol prolonged life and in some instances was curative.The Veterans Administration Cooperative Urological Research Group (VACURG) trials conducted in the 1960s tested this hypothesis.2 The group found that androgen deprivation dramatically relieved the obstructive . . .
Mechanisms of plaque rupture mechanical and biologic interactions
Authors: L Arroyo
Journal: Cardiovascular Research (1999)

Atherosclerotic vascular disease is the most common cause of morbidity and mortality in developed countries, and the world-wide importance of acute vascular syndromes is increasing. Acute events are usually triggered by the development of plaque disruption and subsequent thrombus formation. Histological studies have established specific structural features common among unstable plaques. The plaque has to bear remarkably increased mechanical stress at particular regions, and weakening of the extracellular matrix at these sites leads to fibrous cap rupture. The biologic factors that cause weakening of the plaque at these high stress locations are now emerging. Understanding the interplay of plaque architecture, mechanical properties and matrix biology is critical in the future development of therapies to stabilize lesions.
Thyroid Hormone Receptors: Multiple Forms, Multiple Possibilities*
Authors: MITCHELL A. LAZAR
Journal: Endocrine Reviews (1993)

THE biological importance of the thyroid gland has been recognized for centuries (1). The realization in the late 19th century that cretinism and myxedema result from loss of thyroid function led to the discovery of T4 (2) and T3 (3) as the predominant and most potent thyroid hormones, respectively. During the ensuing decades the plasma membrane (4), synapse (5), endoplasmic reticulum (6), and mitochondria (7) have all been considered as potential cellular sites of action of the thyroid hormones. In the 1960s, however, it was noted that many of the physiological actions of T3 were preceded by nuclear RNA transcription (8, 9), and high-affinity nuclear receptors for T3 were discovered soon thereafter (10,11). The specificity of the nuclear T3 receptors (TRs) for thyroid hormone analogs closely parallels the biological potency of the compounds (12, 13), and the levels of the nuclear TRs correlate well with the developmental and tissue-specific effects of T3 in most cases (14, 15). Thus, although thyroid hormones may have some important nonnuclear actions, the concept that the majority of the actions of T3 are mediated by nuclear TRs was generally accepted by the mid-1980s (16, 17). The discovery of multiple TR isoforms and the characterization of their structure, regulation, properties, and function are the subjects of this review.
Vegetable bezoar simulating a malignant mass in the colon
Authors: N. Akyurek Savas, U. Yilmaz, E. Ozaslan
Journal: Endoscopy (2006)

A bezoar is a tightly packed mass of undigested material that can be found anywhere within the gastrointestinal tract, from the esophagus to the rectum. Bezoars are most commonly found in the stomach but they occasionally form in the colon [1]. We report a 37-year-old man with what appeared to be a colonic mass but which was in fact a bezoar in the transverse colon that had been caused by watermelon.
Corrigendum to ‘Effects of <i>n</i> ‐3 polyunsaturated fatty acids and of rosuvastatin on left ventricular function in chronic heart failure: a substudy of GISSI‐HF trial’ [ <i>Eur J Heart Fail</i> 2010;12:1345‐1353]
Authors: Stefano Ghio, Laura Scelsi, Roberto Latini, Serge Masson, Ermanno Eleuteri, Michela Palvarini, Olga Vriz, Michele Pasotti, Marco Gorini, Roberto Marchioli, Aldo Maggioni, Luigi Tavazzi
Journal: European Journal of Heart Failure (2011)
Culture of synovial cells in vitro. Notes on isolation and propagation.
Authors: J R Fraser, J F McCall
Journal: Annals of the Rheumatic Diseases (1965)

Theculture ofsynovial cells invitro provides a useful meansforthestudyofconnective tissue function. Vaubel (1933) first usedcultures ofsynoviumtoshowthatmucinwassecreted inthejoint itself, aconclusion since confirmed byothers (Kling, Levine, andWise,1955;Castor, 1957;Hedberg andMoritz, 1958; Fischer andTorgerson, 1960). Inrecent years, Castor hasstudied synovial culture extensively ina variety ofaspects (Castor, 1959, 1960,1962;Castor andFries, 1961; Castor and Prince, 1963). Inallthese studies synovial culture hasrelied onthegrowth ofcells frompieces of synovium, orexplants. Inapreliminary report (Fraser andCatt, 1961), wedescribed analternative method fortheharvest ofsynovial intima inamonocellular suspension suitable forculture. Thispaper records ourfurther experience withtheinitial isolationofsynovial cells, andtheir serial propagation beyond thestage ofprimary culture. Evidence is also presented toshowthat thenewmethodismore likely toyield cells derived solely fromthesynovial intima. Certain aspects concerned withspecific experimental applications will bereported indetail later.
Whiplash injury: Author's reply
Authors: P K Newman
Journal: BMJ (1990)

low plasma concentrations of free cyanide dicobalt edetate itself can be toxic.'A second approach is to use sodium nitrite, which converts haemoglobin to methaemoglobin, though in a patient whose oxygen delivery is already compromised by a high carboxyhaemoglobin concentration a further decrease in the haemoglobin available for oxygen transport can be dangerous.We therefore recommend use of the safer intravenous antidote sodium thiosulphate,3 whose distribution is enhanced by the vasodilator amyl nitrite.4
970 PRECLINICAL CHARACTERIZATION OF ABT-072: A NOVEL NON-NUCLEOSIDE HCV POLYMERASE INHIBITOR
Authors: R. Wagner, C. Maring, P. Donner, J. Randolph, A. Krueger, W. Kati, G. Koev, Y. Liu, D. Beno, J. Shen, Y. Gao, Y.Y. Lau, J. Fischer, S. Vaidyanathan, J. Beyer, B.H. Lim, R. Mondal, T. Rockway, J. Pratt, D. Liu, M. Tufano, A. Molla
Journal: Journal of Hepatology (2009)
Systolic direct ventricular interaction affects left ventricular contraction and relaxation in the intact dog circulation.
Authors: B K Slinker, Y Goto, M M LeWinter
Journal: Circulation Research (1989)

Changes in right ventricular systolic function directly influence left ventricular systolic function. Most of our knowledge of this systolic direct ventricular interaction comes from studies of isolated hearts, which suggest that changes in right ventricular size only affect left ventricular systolic function at low pressures and volumes. However, almost nothing is known about systolic direct ventricular interaction in a heart functioning in situ as a part of the intact circulation. We used sudden constriction of the pulmonary artery to assess the immediate effect of a change in right ventricular pressure and contraction pattern on left ventricular contraction and relaxation on the beat following the pulmonary artery constriction in anesthetized open-chest dogs. By focusing on this first beat, we were able to avoid the confounding effect of series ventricular interaction, which changes left ventricular filling and, thus, indirectly influences left ventricular function. At baseline left ventricular end-diastolic pressure of 9.6 +/- 2.1 mm Hg (mean +/- SD), sudden pulmonary artery constriction increased left ventricular peak systolic pressure by 3 +/- 2 mm Hg (2% change), left ventricular stroke volume by 2 +/- 2 ml (8% change), and monoexponential time constant of left ventricular pressure fall during relaxation by 9 +/- 6 msec (22% change). This increased left ventricular relaxation time constant was associated with altered regional segment length changes in the posterior and anterior left ventricular free walls during relaxation. We conclude that systolic direct ventricular interaction affects left ventricular systolic function and relaxation under normal conditions in the intact circulation.
Parkinson's Disease and Movement Disorders
Authors: Charles M. Poser
Journal: JAMA (1989)

This multiauthored volume consisting of 33 different chapters written by 47 authors, including highly respected experts in this field, is a judicious and well-balanced mixture of basic neuroscience regarding the anatomy, physiology, and pharmacology of the basal ganglia and the clinical diagnostic and therapeutic approaches to the various movement disorders. The latter includes discussions of surgical intervention as well as the quite recent neurotransplant approach in the treatment of Parkinson's disease and other neurodegenerative disorders. The largest portion of the book is quite understandably devoted to discussions of parkinsonism. In addition, there are several chapters dealing with topics that are rarely given the consideration they deserve. These include excellent and thorough discussions of tics, akathisia and the restless leg syndrome, cramps, and myalgia, the cognitive impairments associated with Parkinson's disease and other movement disorders, and the different types of myoclonus. There is an informative chapter on magnetic resonance imaging of
"EXCISION OF A V-SHAPED PIECE OF THE LOWER LIP VERSUS ROENTGEN-RAY OR RADIUM TREATMENT"
Authors: Albert Soiland
Journal: JAMA (1923)

<h3>To the Editor:</h3> —The communication appearing inThe Journal, November 24, by Dr. J. C. Bloodgood, with this title is of more than ordinary interest. Dr. Bloodgood divides his cases of lower lip lesions into five classes. For brevity's sake permit me to divide them into three: Lesions primarily and continuously benign. Borderline lesions. Lesions primarily and continuously malignant. It is, of course, recognized that time and conditions may, in a certain proportion of individuals, transform Class 2 into Class 3. Dr. Bloodgood cites one specific instance in which a patient presented a submental metastatic node following successful healing of the primary lesion on the lower lip by radium seven months previously. He makes no mention of such a possibility after a surgical removal, but broadly states that the proper treatment in such cases is a sectional removal by the V-shaped incision, and then makes the astonishing assertion that there
Evaluation of Diabur-Test 5000: A Cooperative Study Carried Out at 12 Diabetes Centers
Authors: D Banauch, P U Koller, W Bablok
Journal: Diabetes Care (1983)

Diabur-Test 5000, a new test strip for urinary glucose, permits the accurate measurement of up to 5% glucose concentrations in urine. In a survey carried out at 12 diabetes centers in Europe, the new test strip was tested in laboratory trials and routine self-monitoring. There was good agreement between the test strip and the quantitative glucose determination on 4105 urine samples in the laboratory trials. A total of 185 patients used Diabur-Test 5000 for self-monitoring; nearly all reported favorably on the new test strip. Both the laboratory tests (on 1677 urine samples) and self-monitoring (on 4309 urine samples) showed Diabur-Test 5000 to be more sensitive compared with other rapid diagnostic tests. The new test strip is highly suitable for the determination of urinary glucose, particularly in routine self-monitoring.
Incoming RNA Virus Nucleocapsids Containing a 5′-Triphosphorylated Genome Activate RIG-I and Antiviral Signaling
Authors: Michaela Weber, Ali Gawanbacht, Matthias Habjan, Andreas Rang, Christoph Borner, Anna Mareike Schmidt, Sophie Veitinger, Ralf Jacob, Stéphanie Devignot, Georg Kochs, Adolfo García-Sastre, Friedemann Weber
Journal: Cell Host & Microbe (2013)
Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis
Authors: Alain Monnereau, Sally L. Glaser, Clayton W. Schupp, Karin Ekström Smedby, Silvia de Sanjosé, Eleanor Kane, Mads Melbye, Lenka Forétova, Marc Maynadié, Anthony Staines, Nikolaus Becker, Alexandra Nieters, Paul Brennan, Paolo Boffetta, Pierluigi Cocco, Ingrid Glimelius, Jacqueline Clavel, Henrik Hjalgrim, Ellen T. Chang
Journal: Blood (2013)
Validation of Diabetic Retinopathy and Maculopathy Diagnoses Recorded in a U.K. Primary Care Database
Authors: Elisa Martín-Merino, Joan Fortuny, Elena Rivero, Luis Alberto García-Rodríguez
Journal: Diabetes Care (2012)

To describe the validity of recorded diabetic retinopathy (DR) and diabetic maculopathy (DMP) diagnoses, including edema (DMO) in The Health Improvement Network (THIN) database.In two independent computer searches, we detected 20,838 patients with diabetes aged 1-84 years with a first DR computer Read entry in 2000-2008 and 4,064 with a first DMP entry. A two-step strategy was used to validate both outcomes as follows: 1) review of patient profiles including free-text comments from primary care practitioners (PCPs) (containing referral information and test results) of a random sample of 500 DR and all DMP computer-detected patients. We classified them in probable, possible, and noncase according to the diagnosis plausibility based on the manual review of the computerized information; and 2) review of questionnaires sent by PCPs and medical records in a random sample (N = 200 for each outcome including 36 diabetic macular edema [DMO]). Gold standard was PCPs' confirmation.After profiles review, we categorized 418 as probable/possible DR. In addition, 3,676 DMP were categorized as probable/possible (including 711 DMO). After review of information sent by PCPs, confirmation rates were 87.3 and 87.2%, respectively (90.3% for DMO). When we applied them to the whole sample of computer-detected patients, the weighted confirmation rate was 78.0% for DR and 78.8% for DMP (86.2% for DMO).Read codes for DR, DM, and DMO are moderately accurate in identifying incident case subjects of these ophthalmologic complications. The validity improved when incorporating PCPs' text comments to the patient's profile. THIN database proved to be a valuable resource to study ophthalmological diabetes complications.
Phasing Out the Freestanding Internship
Authors: Max Michael
Journal: JAMA (1971)

Change of any type—be it in the weather, in politics, in organizational structures or, in our instance, in educational patterns, calls for readjustments and realignments. Changes are accompanied by resistance and hostility on the one hand and by drive and enthusiasm on the other. Those changes that are evolutionary rather than revolutionary are usually more readily accepted. We are concerned with changing patterns in medical education and, germane to this discussion, with changes in the internship. As I will attempt to show, these changes have been evolutionary and, hence, should be more palatable than they seem to be.  In June, 1970, the AMA House of Delegates adopted two recommendations of the Council on Medical Education; to wit: (1) After July 1, 1971, a new internship program shall be approved only after the application contains convincing evidence that the internship and the related residency years will be organized and conducted as
Presence of Children in the Household as a Factor in the Incidence of Paralytic Poliomyelitis in Adults
Authors: Morris Siegel, Morris Greenberg, Jerome Bodian
Journal: New England Journal of Medicine (1957)

IN a recent study on poliomyelitis and pregnancy, a relation was observed between the occurrence of poliomyelitis during gestation and parity.1 Regardless of maternal age, clinical infection was more frequent in multiparous than in primiparous women. The association between parity and poliomyelitis appeared to be dependent, in part, on the number of children in the household. However, the relation could not be explored further because no data on the distribution of the general population by family size were available. They have become available since then.Studies of poliomyelitis in households have been conducted by a number of investigators. Some of . . .
Letter: Lactose intolerance in San populations.
Authors: J M Pettifor, J D Hansen
Journal: BMJ (1974)

a dosage of up to 400 mg daily.This drug is used for its muscle-relaxing properties in tetanus, but it was first introduced into medical practice as a vermifuge.The worm absorbs the drug but, unlike its host, is unable to m,etabolize or excrete it.The anthelmintic property may be related to an anticholinesterase action which upsets the neuromuscular apparatus of the worm or alternatively to an effect on redox systems.These mechanisms might be expected to paralyse the worm, but our experience is that they retain their motility on expulsion in cases of tetanus.It would be helpful if further light could be thrown on this problem.-Weare, etc.,
Abstract 1037: Agents that target the PI3K/mTOR pathway decrease oxygen consumption, reduce tumor hypoxia and improve radiation response in solid tumors.
Authors: George J. Cerniglia, Natalie Daurio, Shannon M. Gallagher-Colombo, Theresa M. Busch, Stephen W. Tuttle, Cameron J. Koch, Alexander Lin, Constantinos Koumenis, Amit Maity
Journal: Cancer Research (2013)

Abstract Hypoxia/anoxia is a well-characterized component of the solid tumor microenvironment and has profound consequences for patient outcome. In particular, clinical data indicate that patients with certain types of tumors treated with radiotherapy have a significantly better outcome if the tumors are less hypoxic. Therefore, we are interested in finding agents that can improve tumor oxygenation. In this study, we investigated the effects of two drugs on tumor oxygenation, NVP-BEZ235 (Novartis), a dual PI3K/mTOR inhibitor, and nelfinavir, an HIV protease inhibitor that inhibits PI3K signaling. Treatment of mice bearing SQ20B head and neck squamous cell carcinoma xenografts with either drug led to a decrease in tumor hypoxia as measured by binding of the 2-nitroimidazole EF3. In vitro O2 consumption measurements of cells grown in tissue culture using a Clark electrode showed that both drugs led to decreased O2 consumption. This result was confirmed using a XF Extracellular Flux Analyzer (Seahorse Bioscience). Using this technique, we found that incubation with NVP-BEZ235 caused a 30- 50% decrease in the oxygen consumption rate (OCR). O2 consumption was stimulated by addition of the uncoupling agent CCCP in both controls and NVP-BEZ235-treated cells, which indicates that they were not killed by NVP-BEZ235 treatment. Similar results were obtained with nelfinavir. In order to identify whether components of the PI3K/mTOR pathway could contribute to the decrease in O2 consumption, we used siRNA directed against either mTOR or the p110alpha subunit of PI3K. Knockdown of either protein led to a decrease in O2 consumption. Studies are ongoing to determine whether the mitochondria are a direct target of NVP-BEZ235 or nelfinavir and if so, which mitochondrial respiratory complex might be affected. In summary, we show that NVP-BEZ235 and nelfinavir, both of which inhibit PI3K signaling, decrease O2 consumption and ameliorate tumor hypoxia. We have found both of these agents to increase radiation response in vivo in animal models, and nelfinavir is currently being used in combination with radiotherapy in clinical trials. These findings offer insight as to how these agents act as radiation response modifiers. Citation Format: George J. Cerniglia, Natalie Daurio, Shannon M. Gallagher-Colombo, Theresa M. Busch, Stephen W. Tuttle, Cameron J. Koch, Alexander Lin, Constantinos Koumenis, Amit Maity. Agents that target the PI3K/mTOR pathway decrease oxygen consumption, reduce tumor hypoxia and improve radiation response in solid tumors. [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 1037. doi:10.1158/1538-7445.AM2013-1037
Acute Kidney Injury After Coronary Artery Bypass Grafting and Long-Term Risk of End-Stage Renal Disease
Authors: Linda Rydén, Ulrik Sartipy, Marie Evans, Martin J. Holzmann
Journal: Circulation (2014)

Background— Acute kidney injury (AKI) is a common complication after coronary artery bypass grafting (CABG) and is associated with adverse outcomes. However, the relationship between AKI after CABG and the long-term risk of end-stage renal disease (ESRD) is unknown. Methods and Results— This study included 29 330 patients who underwent primary isolated CABG in Sweden between 2000 and 2008. AKI was classified according to the Acute Kidney Injury Network (AKIN) classification: stage 1, &gt;0.3 mg/dL (&gt;26 μmol/L) or 50% to 100% increase; stage 2, 100% to 200% increase; and stage 3, &gt;200% increase from the preoperative to postoperative serum creatinine level. Cox proportional hazards regression analysis was used to calculate hazard ratios with 95% confidence intervals for ESRD in AKIN stage 1 and stage 2 to 3. Postoperative AKI occurred in 13% of patients. During a mean follow-up of 4.3±2.4 years, 123 patients (0.4%) developed ESRD, including 50 (1.6%) in AKIN stage 1, 29 (5.2%) in AKIN stage 2 to 3, and 44 (0.2%) without AKI after CABG. After multivariable adjustment, the hazard ratio for ESRD was 2.92 (95% confidence interval, 1.87–4.55) for AKIN stage 1 and 3.81 (95% confidence interval, 2.14–6.79) for AKIN stage 2 to 3. Conclusions— This nationwide study of patients who underwent CABG found that a small increase in the postoperative serum creatinine level was associated with an almost 3-fold increase in the long-term risk of ESRD after adjustment for a number of confounders, including preoperative renal function.
Alefacept for psoriasis and psoriatic arthritis
Authors: A B Gottlieb
Journal: Annals of the Rheumatic Diseases (2005)

Alefacept is a bioengineered fusion protein of soluble lymphocyte function antigen (LFA-3) with Fc fragments of IgG1. It is marketed in many countries for the treatment of moderate to severe psoriasis. This paper reviews the data supporting the use of alefacept in psoriasis and psoriatic arthritis.