tbuckley/cabot-search huggingface dataset:
Breast Cancer Stem Cells and the Epithelial-Mesenchymal Transition.
Authors: R. Weinberg
Journal: Cancer Research (2009)

Abstract The acquisition of highly malignant traits by carcinoma cells is often associated with the activation of a transdifferentiation program termed the epithelial-mesenchymal transition (EMT). The EMT program is deployed in a variety of steps of embryonic morphogenesis, enabling the interconversion of epithelial and mesenchymal cell types. When both normal and neoplastic epithelial cells undergo an EMT, they acquire addition changes in addition to expressing characteristic mesenchymal cell markers. In particular, they acquire motility, an increased resistance to apoptosis and, in the case of carcinoma cells, invasiveness. The motility and invasiveness components associated with the EMT would appear to empower many types of cancer cells to metastasize. An interesting question is how the resulting disseminated cancer cells are able to spawn a macroscopic tumor mass at distant anatomical sites, since this clonal expansion would appear to require an ability to self-renew. Recently, we have examined the cellular products of an EMT. Contrary to our expectations, the resulting cells acquired many of the attributes of stem cells, including the expression of stem cell-associated cell-surface markers. Conversely, mammary epithelial cells that naturally express these markers also express greatly elevated levels of at least four pleiotropically acting transcription factors that have been found able to induce an EMT. More recent studies have confirmed that the product of an EMT in mouse mammary epithelial cells is a cell that has a greatly increased ability to generate an entire mammary ductal epithelial tree. Moreover, we find that cells with the attributes of stem cells exist naturally as minor subpopulations in cultured human mammary epithelial cells. These cells can differentiate spontaneously into non-stem cells and, conversely, the non-stem cells appear capable of dedifferentiating spontaneously into cells with progenitor or stem-cell phenotypes. Hence, the study of certain aspects of mammary epithelial cell biology, including the biology of mammary carcinoma stem cells, may be feasible with cultured cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr A1-1.
BMA chairman has seven point plan for NHS
Authors: L Beecham
Journal: BMJ (1994)

The chairman of the BMA council, Dr Sandy Macara, has proposed a seven point plan to help repair some of the damage which he believes has been done to the NHS by the internal market and the development of a two tier service. “There is despair about the fragmentation of the NHS as competition vanquishes cooperation and privatisation looms large,” he told the BMA's Junior Members Forum at its meeting in Edinburgh last weekend.

All sections of the profession were concerned about the future, Dr Macara said. Students were uncertain about their future careers. Although junior doctors' hours were coming down they were faced with shorter, more intensive training and inadequate consultant expansion. Senior hospital doctors were facing ambitious managers and desperate purchasers strapped for cash. General practitioners have had to cope with a 10% increase in workload and face ever increasing out of hours demands fuelled by the patient's charter. Public health physicians had largely become prisoners of an ideological system which had been their historic duty to challenge, and clinical academic staff were being crippled by performance norms which distorted the balance between teaching, research, and service.

The BMA chairman proposes that the profession should resurrect and reinstate a consensus about its aims and objectives. As a general confession it should join with the government, managers, and the public in declaring its failings and shortcomings.

Secondly, there was a need to restore the objectives which underpinned the consensus, and the profession could use the aims in the Health of the Nation to achieve this.

Thirdly, the profession …
Experience with Mebendazole in Guatemala
Authors: FAITH HAUER
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 March 1981Experience with Mebendazole in GuatemalaFAITH HAUER, R.N.FAITH HAUER, R.N.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-3-415_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the review of mebendazole (1) because here in the Petén of Guatemala we have been using mebendazole in both our mobile clinic and paramedics' program for 3 years. Fortunately, we can purchase this medication at only 40 cents per treatment of six tablets, from a Guatemalan drug company.We agree completely that mebendazole is very effective in the treatment of ascariasis, trichuriasis, and hookworm infections abounding in this area of tropical jungle. However, although the authors mention the problem of "possible" migration ofAscarisduring treatment with mebendazole, they state that "researchers in...Reference1. KEYSTONEMURDOCH JJ. Mebendazole. Ann Intern Med. 1979;91:582-6. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1981Volume 94, Issue 3Page: 415-415KeywordsAllied health care professionalsDrugsHookworms Issue Published: 1 March 1981 PDF DownloadLoading ...
Assessing the Ecotoxicologic Hazards of a Pandemic Influenza Medical Response
Authors: Andrew C. Singer, Vittoria Colizza, Heike Schmitt, Johanna Andrews, Duygu Balcan, Wei E. Huang, Virginie D.J. Keller, Alessandro Vespignani, Richard J. Williams
Journal: Environmental Health Perspectives (2011)

Background: The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers.Objectives: We assessed the ecotoxicologic risks of a pandemic influenza medical response.Methods: To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers.Results: Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0–14% and 5–32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0–14% and 0–30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range).Conclusions: The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity.
Are Pay-for-Performance Programs a Threat to Medical Professionalism?
Authors: Paulette Metoyer
Journal: Annals of Internal Medicine (2008)

Letters15 April 2008Are Pay-for-Performance Programs a Threat to Medical Professionalism?Paulette Metoyer, MDPaulette Metoyer, MDFrom Ann Arbor, MI 48113.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-8-200804150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:It was gratifying to read Snyder and Neubauer's position paper (1) on pay-for-performance and to see that I am not alone in my concerns over these initiatives. I would like to comment on a few issues.First, health care providers are the only certain beneficiaries of pay-for-performance. Therefore, the implementation of pay-for-performance programs, without evidence of patient benefit, is inconsistent with the ethical imperative that “[c]linicians must ensure that … a medically appropriate level of care takes precedence over personal consideration” (1). In that regard, pay-for-performance seems inherently unethical.Second, the goal of reducing substandard care is ...Reference1. Snyder L, Neubauer RL. American College of Physicians Ethics, Professionalism and Human Rights Committee. Pay-for-performance principles that promote patient-centered care: an ethics manifesto. Ann Intern Med. 2007;147:792-4. [PMID: 18056664] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Paulette Metoyer, MDAffiliations: From Ann Arbor, MI 48113.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPay-for-Performance Principles That Promote Patient-Centered Care: An Ethics Manifesto Lois Snyder and Richard L. Neubauer , for the American College of Physicians Ethics, Professionalism and Human Rights Committee* Are Pay-for-Performance Programs a Threat to Medical Professionalism? Christopher M. Lowther Are Pay-for-Performance Programs a Threat to Medical Professionalism? Howard Brody Are Pay-for-Performance Programs a Threat to Medical Professionalism? Richard L. Neubauer and Lois Snyder Metrics Cited byQuality assessment by external bodies: intended and unintended impact on healthcare delivery 15 April 2008Volume 148, Issue 8Page: 629-630KeywordsHealth care qualityHemoglobinHypertensionOverweightPatientsPrevention, policy, and public healthResearch designResearch laboratoriesResidencySub-specialty care ePublished: 15 April 2008 Issue Published: 15 April 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Range of Medicine's Responsibility
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1972)

The London Post this week comments on a letter published on January 7, 1972, in both the Lancet and the British Medical Journal. The reasons for the simultaneous publication must have been weighty, for such distinction is not usually accorded to the urgent revelations, indignant protests, and wry conceits that arrive in the editor's mail. Perhaps the letter was featured by both of Britain's great medical weeklies because it dealt with overpopulation. Perhaps the impressive list of 55 medical signatories was influential. But perhaps most persuasive was the purpose of the letter: to urge and press for action to contain . . .
Florida wins huge award from tobacco firms
Authors: F. B Charatan
Journal: BMJ (1997)

The tobacco industry has agreed to pay the state of Florida $11.3bn (£7.1bn) to settle the legal battle over liability for smoking related illnesses.

After signing the agreement in Palm Beach, Governor Lawton Chiles said: “Our long and difficult four year journey down Tobacco Road has come to a victorious end. The tobacco industry has conceded defeat. We have a settlement of historic proportions.”

The money, to be paid …
Success of maximum likelihood phylogeny inference in the four-taxon case.
Authors: B. S. Gaut, P. O. Lewis
Journal: Molecular Biology and Evolution (1995)

We used simulated data to investigate a number of properties of maximum-likelihood (ML) phylogenetic tree estimation for the case of four taxa. Simulated data were generated under a broad range of conditions, including wide variation in branch lengths, differences in the ratio of transition and transversion substitutions, and the absence of presence of gamma-distributed site-to-site rate variation. Data were analyzed in the ML framework with two different substitution models, and we compared the ability of the two models to reconstruct the correct topology. Although both models were inconsistent for some branch-length combinations in the presence of site-to-site variation, the models were efficient predictors of topology under most simulation conditions. We also examined the performance of the likelihood ratio (LR) test for significant positive interior branch length. This test was found to be misleading under many simulation conditions, rejecting too often under some simulation conditions. Under the null hypothesis of zero length internal branch, LR statistics are assumed to be asymptotically distributed chi 2(1); with limited data, the distribution of LR statistics under the null hypothesis varies from chi 2(1).
Handguns and Homicide
Authors: Charles H. Browning
Journal: JAMA (1976)

Homicide by handgun is a public health problem. No public health-oriented attempts at prevention have been made. A poll of physicians showed strong opinion (1) favoring more stringent controls on the availability of handguns and (2) supporting direct expression of opinion on this issue by physicians within the framework of organized medicine. Physicians can fulfill an obligation to their patients by formulating policy within organized medicine on the handgun issue. (<i>JAMA</i>236:2198-2200, 1976)
Consultation-Liaison Psychiatry 1990
Authors: Z.J. Lipowski
Journal: Psychotherapy and Psychosomatics (1991)

Consultation-liaison (C-L) psychiatry is a subspecialty concerned with clinical service, teaching, and research by psychiatrists in nonpsychiatric health care settings. These activities are focused on the physically ill and on the somatizing patients. The main objective of C-L psychiatry is to maintain a bridge between psychiatry and medicine for the sake of providing biopsychosocial health care. C-L psychiatry's functions include clinical work, teaching, and research at the interface of psychiatry and medicine. This field has grown substantially in the past two decades as is brought out in this article.
Fluticasone Furoate∗ (FF) Nasal Spray-Development of a Next-Generation Delivery System for Allergic Rhinitis [∗USAN approved name]
Authors: W. Berger, J.W. Godfrey, A.C. Grant, A.L. Slater, S.J. Broughton
Journal: Journal of Allergy and Clinical Immunology (2007)
Indicators of Poor Prognosis of Acute Pericarditis
Authors: Massimo Imazio, Enrico Cecchi, Brunella Demichelis, Salvatore Ierna, Daniela Demarie, Aldo Ghisio, Franco Pomari, Luisella Coda, Riccardo Belli, Rita Trinchero
Journal: Circulation (2007)

The clinical search for indicators of poor prognosis of acute pericarditis may be useful for clinical triage of patients at high risk of specific causal conditions or complications. The aim of the present article is to assess the relationship between clinical features at presentation and specific causes or complications.A total of 453 patients aged 17 to 90 years (mean age 52+/-18 years, 245 men) with acute pericarditis (post-myocardial infarction pericarditis was excluded) were prospectively evaluated from January 1996 to August 2004. A specific cause was found in 76 of 453 patients (16.8%): autoimmune in 33 patients (7.3%), neoplastic in 23 patients (5.1%), tuberculous in 17 patients (3.8%), and purulent in 3 patients (0.7%). In multivariable analysis, women (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; P=0.036) and patients with fever >38 degrees C (HR 3.56, 95% CI 1.82 to 6.95; P<0.001), subacute course (HR 3.97, 95% CI 1.66 to 9.50; P=0.002), large effusion or tamponade (HR 2.15, 95% CI 1.09 to 4.23; P=0.026), and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 2.50, 95% CI 1.28 to 4.91; P=0.008) were at increased risk of specific causal conditions. After a mean follow-up of 31 months, complications were detected in 95 patients (21.0%): recurrences in 83 patients (18.3%), tamponade in 14 patients (3.1%), and constriction in 7 patients (1.5%). In multivariable analysis, women (HR 1.65, 95% CI 1.08 to 2.52; P=0.020) and patients with large effusion or tamponade (HR 2.51, 95% CI 1.37 to 4.61; P=0.003) and failure of aspirin or of nonsteroidal anti-inflammatory drugs (HR 5.50, 95% CI 3.56 to 8.51; P<0.001) were at increased risk of complications.Specific clinical features (fever >38 degrees C, subacute course, large effusion or tamponade, and aspirin or NSAID failure) may be useful to identify higher risk of specific causal conditions and complications.
Nephrin loss in experimental diabetic nephropathy is prevented by deletion of protein kinase C alpha signaling in-vivo
Authors: J. Menne, M. Meier, J.-K. Park, M. Boehne, T. Kirsch, C. Lindschau, R. Ociepka, M. Leitges, J. Rinta-Valkama, H. Holthofer, H. Haller
Journal: Kidney International (2006)

Albuminuria in diabetic nephropathy is due to endothelial dysfunction, a loss of negative charges in the basement membrane, and changes a of the slit-membrane diaphragm composition. We have recently shown that protein kinase C alpha (PKCalpha)-deficient mice are protected against the development of albuminuria under diabetic conditions. We here tested the hypothesis that PKCalpha mediates the hyperglycemia-induced downregulation of the slit-diaphragm protein nephrin. After 8 weeks of streptozotocin (STZ)-induced hyperglycemia the expression of glomerular nephrin was significantly reduced. In contrast, other slit-diaphragm proteins such as podocin and CD2AP were unaltered in diabetic state. In PKCalpha-/- mice, hyperglycemia-induced downregulation of nephrin was prevented. Podocin and CD2AP remained unchanged. In addition, the nephrin messenger RNA expression was also reduced in hyperglycemic wild-type mice but remained unaltered in PKCalpha-/- mice. We postulate that the underlying mechanism of the hyperglycemia-induced regulation of various proteins of the glomerular filtration barrier is a PKCalpha-dependent regulation of the Wilms' Tumor Suppressor (WT1) which previously has been shown to act as a direct transcription factor on the nephrin promoter. Our data suggest that PKCalpha activation may be an important intracellular signaling pathway in the regulation of nephrin expression and glomerular albumin permeability in the diabetic state.
Abstract 2247: Torin2 targets mTOR activity and induces apoptosis in DLBCL cells
Authors: Shahab Uddin, Rong Bu, Saravanan Thangavel, Azhar R. Hussain, Khawla S. Al-Kuraya
Journal: Cancer Research (2012)

Abstract The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts as a master switch for cellular anabolic and catabolic processes, regulating the rate of cell growth and proliferation. Dysregulation of the mTOR signaling has been found in many human cancers, including epithelial ovarian cancer, breast cancer, prostate cancer and lung cancer. mTOR has been shown to activate the PI3-kinase/AKT survival pathway and understanding the interplay among signaling molecules in the PI3K/Akt/mTOR pathway is of utmost importance. Two distinct mTOR complexes; mTORC1 and mTORC2, have been identified. mTORC1 is downstream of Akt, sensitive to rapamycin inhibition, and controls cap-dependent protein translation. In contrast, mTORC2 is directly upstream of Akt and is resistant to rapamycin. In order to successfully inhibit mTOR activity, mTORC1 and 2 have to be simultaneously inhibited at the same time to effectively induce apoptosis. The role of mTOR in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. Therefore, we examined the effect of a new generation mTOR inhibitor (Torin2) on a panel of DLBCL cell lines. We found that Torin2 treatment inhibited cell viability and induced apoptosis in DLBCL cell lines in a dose dependent manner with an IC50 of 53nM. In addition, Torin2 also activated the mitochondrial apoptotic pathway by causing changes in the mitochondrial membrane potential, activation of caspase-9 and -3 and cleavage of PARP. Finally, Torin2 treatment of DLBCL cell lines also down-regulated the expression of inhibitor of apoptosis proteins (IAPs); XIAP and Survivin in a dose dependent manner. As mTOR has been shown to activate down stream targets such as p70S6 as well as up-stream targets such AKT, we will further investigate the effect of Torin2 treatment on these targets. In addition, we will also determine whether Torin2 treatment causes disruption of cross talk between mTOR and PI3-kinase/AKT pathways. These studies will give us an insight on the molecular relationship between these survival pathways and may detect newer survival molecules that can be targeted for efficient treatment of these cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2247. doi:1538-7445.AM2012-2247
Meta-analysis of Empirical Long-term Antiarrhythmic Therapy After Myocardial Infarction
Authors: Louis K. Hine
Journal: JAMA (1989)

SUDDEN cardiac death remains a major cause of mortality and a significant public health concern. At least 40% of sudden deaths occur in people with clinically overt heart disease, and among patients with coronary heart disease, the risk of sudden death is relatively greater for those patients who have had a myocardial infarction (MI) than for those who have not. 1 Approximately 50% of MI-related deaths are sudden and usually caused by ventricular arrhythmias. 2,3 Although the majority of these deaths occur in the earliest phases of MI, 4 the risk of mortality beyond 1 year after MI remains four to eight times greater than that for comparable patients who did not have an MI. 5,6 Approximately 35% to 40% of deaths that occur late after MI will be caused by sudden death. 7   The presence of premature ventricular contractions (PVCs) after MI has been shown to be a risk
Radionuclide Bone Imaging in Erdheim-Chester Disease
Authors: Rodolfo N????ez, Gene G. Tronco, Josephine N. Rini, Joshua Hofman, Michel Amoashiy, Tawfiqul Bhuiya, Christopher J. Palestro
Journal: Clinical Nuclear Medicine (2004)

Erdheim-Chester disease is a rare sporadic systemic histiocytic disease of unknown etiology that routinely involves the diametaphyseal region of the long bones of the appendicular skeleton. In addition, there is frequent involvement of multiple internal organs producing protean manifestations. Although definitive diagnosis requires histopathologic confirmation, its appearance on bone scintigraphy is virtually pathognomonic of this entity. We report the case of a 53-year-old man with Erdheim-Chester disease who presented with lower extremity bone pain and was found to have the characteristic lesions of this condition on bone scintigraphy.