tbuckley/cabot-search huggingface dataset:
Cancer Stem Cells and Aneuploid Populations within Developing Tumors Are the Major Determinants of Tumor Dormancy
Authors: Anjali P. Kusumbe, Sharmila A. Bapat
Journal: Cancer Research (2009)

Tumor formation involves substantial cell division and genetic instability, but the relationship between quiescent cancer stem cells (CSC) and dividing progenitors in these events is poorly understood. Likewise, the implication of aneuploid cells in solid tumors is uncertain. CSCs are postulated to contribute to tumor dormancy and present a formidable obstacle in limiting treatment outcomes for a majority of cancers, whereas the genetic heterogeneity conjured by aneuploid cells may influence tumor drug resistance. However, direct confirmation of these events remains forthcoming. In the present study, we addressed the identification of tumor dormancy in terms of isolation of therapy-refractory residual tumor cells from tumors that persist in a state of quiescence as label-retaining cells. The choices of label were PKH67/PKH26 dyes that irreversibly bind to the lipid bilayer on cell membranes and get equally partitioned among daughter cells subsequent to each cell division. Consequent characterization revealed that label-retaining cells encompass two different populations capable of remaining in a state of quiescence, i.e., stem-like cells and aneuploid cells. The former express a reversibility of quiescence through retention of functionality and also exhibit therapeutic refractoriness; the latter seem to be either quiescent or proliferation-arrested at steady-state. Subsequent to exposure to selective pressure of chemotherapy, a fraction of these cells may acquire the potential to proliferate in a drug-refractory manner and acquire stem-like characteristics. Collectively, the findings of the present study reveal that tumor-derived CSCs and aneuploid populations contribute to drug resistance and tumor dormancy in cancer progression.
Low-Dose Computed Tomography Screening for Lung Cancer
Authors: Steven H. Woolf, Russell P. Harris, Doug Campos-Outcalt
Journal: JAMA Internal Medicine (2014)

In 2013, the US Preventive Services Task Force (USPSTF) recommended low-dose computed tomographic (CT) screening for high-risk current and former smokers with a B recommendation (indicating a level of certainty that it offered moderate to substantial net benefit). Under the Affordable Care Act, the USPSTF recommendation requires commercial insurers to fully cover low-dose CT. The Centers for Medicare &amp; Medicaid Services (CMS) is now considering whether to also offer coverage for Medicare beneficiaries. Although the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose CT, implementation of national screening may be premature. The magnitude of benefit from routine screening is uncertain; estimates are based on data from a single study and simulation models commissioned by the USPSTF. The potential harms—which could affect a large population—include false-positive results, anxiety, radiation exposure, diagnostic workups, and the resulting complications. It is unclear if routine screening would result in net benefit or net harm. The NLST may not be generalizable to a national screening program for the Medicare age group because 73% of NLST participants were younger than 65 years. Moreover, screening outside of trial conditions is less likely to be restricted to high-risk smokers and qualified imaging centers with responsible referral protocols. Until better data are available for older adults who are screened in ordinary (nontrial) community settings, CMS should postpone coverage of low-dose CT screening for Medicare beneficiaries.
More on Medical Malpractice
Authors: Janardan D. Khandekar
Journal: Annals of Internal Medicine (1993)

Letters1 June 1993More on Medical MalpracticeJanardan D. Khandekar, MD and Gershon Y. Locker, MDJanardan D. Khandekar, MDSearch for more papers by this author and Gershon Y. Locker, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-11-199306010-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with great interest and considerable apprehension the article [1] and accompanying editorial [2] on medical malpractice. Dividing the number of claims filed in New Jersey over a 15-year period (11934) by the number of physicians insured (12829) yields an average of 1 case per practicing physician. Further, payment was made in 43% of the cases. If New Jersey is representative of the whole country, then over a 15-year period, 40% of the physicians will have a liability claim against them. Over the professional life time of a physician, there is almost a 100% guarantee that ...References1. Taragin MI, Willett LR, Wilczek AP, Trout R, Carson JL. The influence of standard of care and severity of injury on the resolution of medical malpractice claims. Ann Intern Med. 1992; 117:780-4. Google Scholar2. Bovbjerg RR. Medical malpractice: folklore, facts, and the future. Ann Intern Med. 1992; 117:788-91. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1993Volume 118, Issue 11Page: 909-910KeywordsCrime Issue Published: 1 June 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Disinfection with Formaldehyd.
Authors: James A. Egan
Journal: JAMA (1906)

Springfield, Aug. 13, 1906. <h3>To the Editor:</h3> —InThe Journal, July 28, page 288, under the above caption, Dr. Henry Albert refers to an article appearing inThe Journal, July 14, page 139, concerning experiments made by the Illinois Board of Health. Dr. Albert says of the potassium permanganate method of liberating gas: "It is impossible to evaporate a pint of the 40 per cent, solution of formaldehyd with 3½ oz. of potassium permanganate. To do this it will require from 6 to 6% oz., and with the use of any less the disinfection, I am sure, will not be satisfactory." I have not found this to be the case. In many experiments conducted by the Illinois State Board of Health during the past year with this method of disinfection it has been found that while 3½ oz. of the permanganate would not fully evaporate 16 oz. of the 40
Science, medicine, and the future : Hypertension
Authors: M. J Brown
Journal: BMJ (1997)

<h3>Abstract</h3> The abundance of drugs now available for treating hypertension, and evidence that small reductions in blood pressure reverse the associated risk of stroke have shifted clinical concerns away from hypertension. However, we do not understand the cause of hypertension in 95% of patients, fail to achieve a normal blood pressure in 50% of patients, and are unable fully to reverse the cardiac and vascular changes that predate the diagnosis and treatment of hypertension. Consequently, hypertension remains the commonest cause of strokes in Britain and of renal failure in the United States. Essential hypertension is a polygenic disease whose understanding can now be advanced through molecular genetic analyses. Several different syndromes are likely to be recognised; most will be due to interactions between genetic and environmental factors, but there are also likely to be further monogenic syndromes in families with multiple affected members. Recognition of these syndromes will permit accurate genetic prediction of prognosis and optimal treatment and perhaps lead to new and more powerful classes of antihypertensive treatment.
The Rise of Surgery: From Empiric Craft to Scientific Discipline
Authors: Lloyd M. Nyhus
Journal: JAMA (1979)

The Wangensteens have approached this broad subject from a new perspective, a look at the operations performed through the centuries, particularly operations developed for diseases or conditions of urgency. Thus, chapters include "Wound Management in Amputation," "Debridement," "Lithotomy and Lithotomists," "Tracheostomy and Respiratory Obstruction," "Ectopic Pregnancy," "Surgery of War," and 20 other fascinating presentations. The first presentation is entitled "Overview," and the last chapter is "Retrospect and Prospect." While the first chapter gives in capsule form highlights of the importance of anesthesia, antisepsis, and antibiotics, with detailed information to be found in separate chapters, the last chapter gives that special philosophy found only in a surgical educator and research scientist with decades of experience. A "picky" reviewer might fault the authors for being a bit colloquial in the choice of some 20th century historical highlights. But suffice it to say that the original contributions of the Minnesota group during Professor
Transverse myelitis unlikely to be due to measles, mumps, and rubella vaccine
Authors: R. Fescharek, H. Dass
Journal: BMJ (1995)

EDITOR,--K A Joyce and J E Rees report on a 20 year old man who developed subacute transverse myelitis two to three weeks after immunisation with measles, mumps, and rubella vaccine.1 Five days after vaccination he developed a feverish exanthematous disease, which fluctuated for two weeks and preceded the onset of the neurological symptoms. Postvaccination transverse myelitis was diagnosed when a significant rise in titres of rubella antibodies was …
Environmental Impact on Vascular Development Predicted by High-Throughput Screening
Authors: Nicole C. Kleinstreuer, Richard S. Judson, David M. Reif, Nisha S. Sipes, Amar V. Singh, Kelly J. Chandler, Rob DeWoskin, David J. Dix, Robert J. Kavlock, Thomas B. Knudsen
Journal: Environmental Health Perspectives (2011)

Understanding health risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. High-throughput screening (HTS) in the U.S. Environmental Protection Agency (EPA) ToxCast™ project provides vast data on an expanding chemical library currently consisting of > 1,000 unique compounds across > 500 in vitro assays in phase I (complete) and Phase II (under way). This public data set can be used to evaluate concentration-dependent effects on many diverse biological targets and build predictive models of prototypical toxicity pathways that can aid decision making for assessments of human developmental health and disease.We mined the ToxCast phase I data set to identify signatures for potential chemical disruption of blood vessel formation and remodeling.ToxCast phase I screened 309 chemicals using 467 HTS assays across nine assay technology platforms. The assays measured direct interactions between chemicals and molecular targets (receptors, enzymes), as well as downstream effects on reporter gene activity or cellular consequences. We ranked the chemicals according to individual vascular bioactivity score and visualized the ranking using ToxPi (Toxicological Priority Index) profiles.Targets in inflammatory chemokine signaling, the vascular endothelial growth factor pathway, and the plasminogen-activating system were strongly perturbed by some chemicals, and we found positive correlations with developmental effects from the U.S. EPA ToxRefDB (Toxicological Reference Database) in vivo database containing prenatal rat and rabbit guideline studies. We observed distinctly different correlative patterns for chemicals with effects in rabbits versus rats, despite derivation of in vitro signatures based on human cells and cell-free biochemical targets, implying conservation but potentially differential contributions of developmental pathways among species. Follow-up analysis with antiangiogenic thalidomide analogs and additional in vitro vascular targets showed in vitro activity consistent with the most active environmental chemicals tested here.We predicted that blood vessel development is a target for environmental chemicals acting as putative vascular disruptor compounds (pVDCs) and identified potential species differences in sensitive vascular developmental pathways.
Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation
Authors: P. Sauer, F. Chahoud, D. Gotthardt, W. Stremmel, K.-H. Weiss, M. Büchler, P. Schemmer, J. Weitz, A. Schaible
Journal: Endoscopy (2012)

In the present study we prospectively evaluated the safety and efficacy of temporary fully covered, self-expandable metal stents (fcSEMS) to treat biliary strictures (n = 9), leaks (n = 9), and combined lesions (n = 1) occurring after liver transplantation, when standard endoscopic attempts had failed. Placement of fcSEMS and their removal in scheduled patients were successful and without complications. Resolution of the biliary lesion was confirmed in 15 of 19 patients (79 %). Treatment was not successful in two patients and not evaluable in 2 other patients. Complications occurred in 9 /19 patients (47 %): stent migration in 6, stent occlusion in 1, and de novo stricture after successful treatment of a biliary leak in 2. After a median follow-up of 12 months, one recurrent anastomotic stricture was noted. Temporary placement of fcSEMS in biliary strictures and leaks after liver transplantation provides satisfactory results even in patients who have undergone multiple previous conventional endoscopic attempts, and offers an alternative approach to surgical intervention.
False-Negative Bone Imaging Due to Etidronate Disodium Therapy
Authors: ARTHUR Z. KRASNOW, B DAVID COLLIER, ALI T. ISITMAN, ROBERT S. HELLMAN, DAVID EWEY
Journal: Clinical Nuclear Medicine (1988)

A 77-year-old man wilh prostate cancer was serially evaluated for bone metastases using Tc-99m methylene disphosphonate (Tc-99m MOP) both on and off treatment with etidronate disodium (EHDP). While the patient was receiving the medication only minimal bony uptake ot the tracer was seen with the majority remaining in the soft tissues. The similarly structured EHDP probably saturated the binding sites that the radioactive MDP usually adheres to. Physicians should be aware of this interaction and may have to wait until the EHDP has been discontinued for several months before performing bone imaging on these patients.
Coronary Artery Fistula
Authors: Meng-Ling Chen, Hung-Shun Lo, Hung-Yi Su, Ing-Ming Chao
Journal: Clinical Nuclear Medicine (2009)

Coronary artery fistula is an unusual coronary artery anomaly. Cardiac catheterization with coronary angiography remains the gold standard for the diagnosis of coronary artery fistula, but the physiologic significance and the relationship of coronary artery fistulas to other structures may not be apparent when it is investigated with this technique. Cardiac multidetector computed tomography and stress myocardial perfusion SPECT can be used as adjuncts to coronary angiography for anatofunctional evaluation of this anomaly. We report the case of a 25-year-old male patient with effort angina in whom cardiac multidetector computed tomography and dipyridamole Tl-201 myocardial SPECT were shown to play an important role in the noninvasive evaluation of coronary artery fistula and provide a physiology-based decision-making assessment for determining the need for intervention of such an anomaly.
Antidiabetic effects of dipeptidyl peptidase–IV inhibitors and sulfonylureas in streptozotocin-nicotinamide–induced mildly diabetic mice
Authors: Akiko Matsuyama-Yokono, Atsuo Tahara, Ryosuke Nakano, Yuka Someya, Katsuhisa Shiraki, Masahiko Hayakawa, Masayuki Shibasaki
Journal: Metabolism (2009)
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Authors: Joseph L. Evans, Ira D. Goldfine, Betty A. Maddux, Gerold M. Grodsky
Journal: Endocrine Reviews (2002)

Abstract In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA). Recent evidence suggests that common stress-activated signaling pathways such as nuclear factor-κB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases underlie the development of these late diabetic complications. In addition, in type 2 diabetes, there is evidence that the activation of these same stress pathways by glucose and possibly FFA leads to both insulin resistance and impaired insulin secretion. Thus, we propose a unifying hypothesis whereby hyperglycemia and FFA-induced activation of the nuclear factor-κB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways, along with the activation of the advanced glycosylation end-products/receptor for advanced glycosylation end-products, protein kinase C, and sorbitol stress pathways, plays a key role in causing late complications in type 1 and type 2 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes. Studies with antioxidants such as vitamin E, α-lipoic acid, and N-acetylcysteine suggest that new strategies may become available to treat these conditions.
Oxygen Activates the Rho/Rho-Kinase Pathway and Induces RhoB and ROCK-1 Expression in Human and Rabbit Ductus Arteriosus by Increasing Mitochondria-Derived Reactive Oxygen Species
Authors: Hidemi Kajimoto, Kyoko Hashimoto, Sandra N. Bonnet, Alois Haromy, Gwyneth Harry, Rohit Moudgil, Toshio Nakanishi, Ivan Rebeyka, Bernard Thébaud, Evangelos D. Michelakis, Stephen L. Archer
Journal: Circulation (2007)

Constriction of the ductus arteriosus (DA) is initiated at birth by inhibition of O2-sensitive K+ channels in DA smooth muscle cells. Subsequent membrane depolarization and calcium influx through L-type calcium channels initiates functional closure. We hypothesize that Rho-kinase activation is an additional mechanism that sustains DA constriction.The effect of increased PO2 on the activity and expression of Rho-kinase was assessed in DAs from neonates with hypoplastic left-heart syndrome (n=15) and rabbits (339 term and 99 preterm rabbits). Rho-kinase inhibitors (Y-27632 and fasudil) prevent and reverse O2 constriction. Heterogeneity exists in the sensitivity of constrictors (PO2=endothelin=phenylephrine>KCl) and of fetal vessels (DA=pulmonary artery>aorta) to Rho-kinase inhibition. Inhibition of L-type calcium channels (nifedipine) or removal of extracellular calcium inhibits approximately two thirds of O2 constriction. Residual DA constriction reflects calcium sensitization, which persists after removal of extracellular calcium and blocking of sarcoplasmic reticulum Ca2+-ATPase. In term DA, an increase in PO2 activates Rho-kinase and thereby increases RhoB and ROCK-1 expression. Activation of Rho-kinase in DA smooth muscle cells is initiated by a PO2-dependent, rotenone-sensitive increase in mitochondrion-derived reactive O2 species. O2 effects on Rho-kinase are mimicked by exogenous H2O2. In preterm DAs, immaturity of mitochondrial reactive oxygen species generation is associated with reduced and delayed O2 constriction and lack of PO2-dependent upregulation of Rho-kinase expression.O2 activates Rho-kinase and increases Rho-kinase expression in term DA smooth muscle cells by a redox-regulated, positive-feedback mechanism that promotes sustained vasoconstriction. Conversely, Rho-kinase inhibitors may be useful in maintaining DA patency, as a bridge to congenital heart surgery.
Profibrinolysin, Antifibrinolysin, Fibrinogen and Urine Fibrinolytic Factors in the Human Subject1
Authors: M. Mason Guest
Journal: Journal of Clinical Investigation (1954)

This report describes methods for the quantitative assay of human plasma profibrinolysin (plasminogen) and for the semi-quantitation of fibrinolytic factors in urine. The concentrations of plasma profibrinolysin, antifibrinolysin, fibrinogen and lytic factors in urine of patients with an active neoplasm and in pregnant women are compared with their concentrations in normal individuals.
Functional, angiographic and intracoronary doppler flow characteristics in symptomatic patients with myocardial bridging: Effect of short-term intravenous beta-blocker medication
Authors: Ernst R. Schwarz, Heinrich G. Klues, Jürgen vom Dahl, Ilona Klein, Winfried Krebs, Peter Hanrath
Journal: Journal of the American College of Cardiology (1996)
Determinants and Prognostic Impact of Heart Failure Complicating Acute Coronary Syndromes
Authors: Philippe Gabriel Steg, Omar H. Dabbous, Laurent J. Feldman, Alain Cohen-Solal, Marie-Claude Aumont, José López-Sendón, Andrzej Budaj, Robert J. Goldberg, Werner Klein, Frederick A. Anderson
Journal: Circulation (2004)

Background— Few data are available on the impact of heart failure (HF) across all types of acute coronary syndromes (ACS). Methods and Results— The Global Registry of Acute Coronary Events (GRACE) is a prospective study of patients hospitalized with ACS. Data from 16 166 patients were analyzed: 13 707 patients without prior HF or cardiogenic shock at presentation were identified. Of these, 1778 (13%) had an admission diagnosis of HF (Killip class II or III). HF on admission was associated with a marked increase in mortality rates during hospitalization (12.0% versus 2.9% [with versus without HF], P &lt;0.0001) and at 6 months after discharge (8.5% versus 2.8%, P &lt;0.0001). Of note, HF increased mortality rates in patients with unstable angina (defined as ACS with normal biochemical markers of necrosis; mortality rates: 6.7% with versus 1.6% without HF at admission, P &lt;0.0001). By logistic regression analysis, admission HF was an independent predictor of hospital death (odds ratio, 2.2; P &lt;0.0001). Admission HF was associated with longer hospital stay and higher readmission rates. Patients with HF had lower rates of catheterization and percutaneous cardiac intervention, and fewer received β-blockers and statins. Hospital development of HF (versus HF on presentation) was associated with an even higher in-hospital mortality rate (17.8% versus 12.0%, P &lt;0.0001). In patients with HF, in-hospital revascularization was associated with lower 6-month death rates (14.0% versus 23.7%, P &lt;0.0001; adjusted hazard ratio, 0.5; 95% CI, 0.37 to 0.68, P &lt;0.0001). Conclusions— In this observational registry, heart failure was associated with reduced hospital and 6-month survival across all ACS subsets, including patients with normal markers of necrosis. More aggressive treatment of these patients may be warranted to improve prognosis.
The anticancer immune response: indispensable for therapeutic success?
Authors: Laurence Zitvogel, Lionel Apetoh, François Ghiringhelli, Fabrice André, Antoine Tesniere, Guido Kroemer
Journal: Journal of Clinical Investigation (2008)

Although the impact of tumor immunology on the clinical management of most cancers is still negligible, there is increasing evidence that anticancer immune responses may contribute to the control of cancer after conventional chemotherapy. Thus, radiotherapy and some chemotherapeutic agents, in particular anthracyclines, can induce specific immune responses that result either in immunogenic cancer cell death or in immunostimulatory side effects. This anticancer immune response then helps to eliminate residual cancer cells (those that fail to be killed by chemotherapy) or maintains micrometastases in a stage of dormancy. Based on these premises, in this Review we address the question, How may it be possible to ameliorate conventional therapies by stimulating the anticancer immune response? Moreover, we discuss the rationale of clinical trials to evaluate and eventually increase the contribution of antitumor immune responses to the therapeutic management of neoplasia.