tbuckley/cabot-search huggingface dataset:
Low Platelet Counts in Cancer Patients: Should Heparin for Venous Thromboembolism Prophylaxis Be Instituted?
Authors: Nishith K. Singh, Gaurav Sangwan
Journal: Journal of Clinical Oncology (2008)

Society of Clinical Oncology Guideline Recommendations for Prophylaxis of Venous Thromboembolism do not comment on the indications for heparin in patients with thrombocytopenia, which is common among patients with malignancy. 1 We recently witnessed a hospitalized patient with acute leukemia and platelet levels of 18,000/mm 3 who developed an acute upper extremity deep vein thrombus.Although in her case, it was clearly related to a peripherally inserted central catheter in the affected limb, we wonder if it demonstrates her being at a considerably high risk for spontaneous thromboembolic events.The treating team could not gather sufficient evidence to institute prophylactic dosage of heparin in view of her high presumed risk of bleeding.Two out of the three major randomized, double-blind, placebo-controlled trials on thromboembolism prophylaxis in hospitalized patients (the Prophylaxis in Medical Patients with Enoxaparin trial and the Prevention of Recurrent Venous Thromboembolism study), have specifically excluded patients with platelet counts less than 100,000/mm 3 . 2,3 As such, evidence for thromboembolism prophylaxis in patients with platelet count less than 100,000/mm 3 is probably not clear.Should thrombocytopenia be a contraindication for heparin prophylaxis?At what level of the quantitative defect should prophylaxis be safely withheld?We seek authors' expert opinion on this matter of importance.
Abstract 3150: miR-100 in ovarian cancer cell lines
Authors: Viive M. Howell, Kristie-Ann Dickson, Casina W. S. Kan, Michael A. Hahn, Deborah J. Marsh
Journal: Cancer Research (2012)

Abstract MicroRNA (miRNA), small non-coding RNA sequences that regulate gene expression, have the potential to function as tumor suppressors or oncogenes. To determine the contribution of miRNA to ovarian oncogenesis this project sought to identify dysregulated miRNA and their targets in ovarian cancer cell lines. miRNA expression profiling was performed on 6 serous epithelial ovarian cancer (SEOC) cell lines and normal ovarian surface epithelial (OSE) cells. miRNAs differentially expressed between SEOC and OSEs were selected for further analyses and candidate target genes identified by prediction algorithms. miRNA expression was restored by transient transfection of miRNA mimics or stable transduction of lentiviral vectors expressing miRNA precursors. The effects on the expression of 2 predicted targets, SMARCA5 and FRAP1, were investigated using a luciferase reporter system, quantitative RT-PCR (qPCR) and immunoblotting. The effect of miRs on cellular proliferation was also explored. Expression profiling identified miR-100 as having &amp;gt;5-fold lower expression in SEOC vs OSE cells. Seed sequences or binding sites for miR-100 were identified in the 3′UTRs of SMARCA5 and FRAP1. Using a luciferase expression system in OVCAR-3 cells, a miR-100 mimic repressed expression of SMARCA5 3′UTR by 40 % (p&amp;lt;0.0001), and FRAP1 3′UTR by 30% (p&amp;lt;0.0005). No effect of the mimic was observed when the predicted miR-100 binding sites in each gene's 3′UTR were mutated. Stable transduction of OV202 cells with pre-miR-100 resulted in a 3-5 fold increase in miR-100 expression. This stably transduced SEOC cell line showed decreased cellular proliferation, and repressed transcript and protein levels of SMARCA5/SNF2H and FRAP1/mTOR compared with the cell line transduced with the empty lentiviral vector. We identified miR-100 as a modulator of cellular proliferation in OV202 cells, possibly through regulation of SNF2H, a chromatin remodelling factor, and mTOR a phosphatidylinositol kinase-related kinase. miR-100 is located in an area of frequent chromosomal loss in aggressive SEOC suggesting a mechanism for reduced expression in these cells. Future work will investigate the potential of miR-100 as a novel therapeutic target for the treatment of ovarian cancer. 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 3150. doi:1538-7445.AM2012-3150
Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac β-myosin gene mutations
Authors: O Havndrup
Journal: Cardiovascular Research (2003)

Objective: Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in genes encoding cardiac sarcomere proteins. Although available, genetic analyses are generally not used clinically. In the present study, we evaluated the outcome of clinical vs. genetic screening of family members with specific focus on mutations in the cardiac β-myosin heavy chain (MYH7) gene. Methods: A consecutive cohort of 68 FHC probands and their families (395 persons) of Danish origin was evaluated including patient- and family histories, physical examinations, electrocardiogram and echocardiography. Mutation screening was performed by a combination of single strand conformation/heteroduplex analysis and direct sequencing. Results: Eight different MYH7 gene mutations were identified in nine (13%) families (96 persons). In eight (89%) of the families, major cardiac events had occurred. Myectomy or percutaneous septal alcohol ablation had been performed in a higher number of MYH7 probands i.e. in five of nine (56%) as compared to 10 of 59 (17%) (P<0.05) non-MYH7 mutation probands. Neither echocardiographic nor ECG findings were useful to distinguish MYH7 from non-MYH7 probands. Between adult MYH7 mutation-carriers (n=38) and their non-carrier relatives (n=39), low sensitivity and specificity of the clinical diagnostic criteria tested were observed and minor clinical diagnostic criteria alone were not useful for identification of mutation carriers. By genetic screening of relatives with no or only minor hypertrophy on echocardiography, i.e. a priori possible mutation-carriers normally recommended clinical follow-up—the diagnosis was excluded in 52 (83%) persons. In addition, six relatives with secondary hypertrophy were identified as non-carriers. Conclusion: Neither echocardiographic nor ECG findings were useful to distinguish MYH7 from non-MYH7 probands. Extension of screening to include genetic analyses offered a marked diagnostic advantage as compared to clinical screening alone in FHC families.
Studies with Radioactive Endotoxin. II. Correlation of Physiologic Effects with Distribution of Radioactivity in Rabbits Injected with Lethal Doses of E. Coli Endotoxin Labelled with Radioactive Sodium Chromate1
Authors: A. I. Braude, F. J. Carey, Margaret Zalesky
Journal: Journal of Clinical Investigation (1955)

The development of a simple technique for la- belling E. coli endotoxin with radioactive chro- mium has presented the opportunity for tracer ex- periments (1).Such experiments have been conducted in different species of animals, using various doses of endotoxin tagged with either hex- avalent chromium as Na2Cr510, or trivalent chromium, as Cr1Cl,.One of the objectives was to observe the physiologic changes which un- fold as the endotoxin is removed from the blood and deposited in various organs.This paper presents the first of a series of studies describing these changes; it deals with the injection into rab- bits of lethal doses of endotoxin tagged with hexavalent radiochromium. METHODSEndotoxin, prepared from bacteria grown in syn- thetic medium, was labelled by direct incubation with Na.CrmO4 by the method described in the preceding paper (1).When injected into rabbits, there were 223.4 counts per second per mg.and the LD. for mice before and af- ter tagging was 0.2 mg.Three groups of adult rabbits weighing 2.5 to 3.0 kg. were injected intravenously with Cr' as follows:Group I-Endotoxin labelled with NaCrO4.Group II-NaCr'O4 in one vein followed by the in- jection of unlabelled endotoxin in another vein.Group III-Na2Cr'O4 only (no endotoxin).The dose of endotoxin and chromium is given for each group in Tables IA, IB, IC and Figures IA, 1B, 1C.The dose of radioactive endotoxin was selected after determin- ing from preliminary experiments: 1) that the pattern of distribution of radioactivity was the same over a wide range of lethal doses, and 2) that the amount of radio- active endotoxin injected in these experiments was enough to provide accurate counts in the tissues with- out killing the animals in too short a time to complete the experiment.
Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia
Authors: Nuria Oliva, Maria Carcole, Margarita Beckerman, Sivan Seliktar, Alison Hayward, James Stanley, Nicola Maria Anne Parry, Elazer R. Edelman, Natalie Artzi
Journal: Science Translational Medicine (2015)

A "one material fits all" mindset ignores profound differences in target tissues that affect their responses and reactivity. Yet little attention has been paid to the role of diseased tissue on material performance, biocompatibility, and healing capacity. We assessed material-tissue interactions with a prototypical adhesive material based on dendrimer/dextran and colon as a model tissue platform. Adhesive materials have high sensitivity to changes in their environment and can be exploited to probe and quantify the influence of even subtle modifications in tissue architecture and biology. We studied inflammatory colitis and colon cancer and found not only a difference in adhesion related to surface chemical interactions but also the existence of a complex interplay that determined the overall dendrimer/dextran biomaterial compatibility. Compatibility was contextual, not simply a constitutive property of the material, and was related to the extent and nature of immune cells in the diseased environment present before material implantation. We then showed how to use information about local alterations of the tissue microenvironment to assess disease severity. This in turn guided us to an optimal dendrimer/dextran formulation choice using a predictive model based on clinically relevant conditions.
Inappropriate Prescribing of Psychoactive Drugs
Authors: STUART L. NIGHTINGALE
Journal: Annals of Internal Medicine (1975)

Editorials1 December 1975Inappropriate Prescribing of Psychoactive DrugsSTUART L. NIGHTINGALE, M.D., ROBERT A. DORMER, J.D., ROBERT L. DUPONT, M.D.STUART L. NIGHTINGALE, M.D., ROBERT A. DORMER, J.D., ROBERT L. DUPONT, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-6-896 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMost of the current great concern about the inappropriate prescribing of psychoactive drugs is focused on the issue of overprescribing. A consensus is lacking, however, on the extent of overprescribing or on the relative responsibilities of physicians, patients, and drug manufacturers for the overprescribing that is done (1, 2). Some excess prescribing can be ascribed to physicians with impaired judgment from organic or psychiatric causes and some to physicians who unscrupulously prescribe psychoactive drugs for profit. This second group is probably responsible for only a small fraction of inappropriate prescriptions, but, in communities, these few individuals can initiate and maintain...References1. MARONDELEEMCCARRON RPM: A study of prescribing patterns. Med Care 9:383-395, 1971 CrossrefMedlineGoogle Scholar2. PARRYBALTERMELLINGER HMG: National patterns of psychotherapeutic drug use. Arch Gen Psychiatry 28:769-783, 1971 CrossrefGoogle Scholar3. EDISON G: Amphetamines: a dangerous illusion. Ann Intern Med 74:605-610, 1971 LinkGoogle Scholar4. : Barbiturates and barbiturate-like drugs. Considerations in their medical use. JAMA 230:1440-1441, 1974 CrossrefMedlineGoogle Scholar5. GREENBLATTSHADER DR: Benzodiazepines. N Engl J Med 291:1011-1015, 1239-1243, 1974 CrossrefMedlineGoogle Scholar6. CNS Depressants. Technical Papers, no. 1, National Clearing-house for Drug Abuse Information. Washington, D.C., Superintendent of Documents, U.S. Government Printing Office, 1974 Google Scholar7. Amphetamines. Report Series, series 28, no. 1, National Clearing-house for Drug Abuse Information. Washington, D.C., Superintendent of Documents, U.S. Government Printing Office, 1974 Google Scholar8. Compliance Investigations Division, Registrant Information, Drug Enforcement Administration, 1405 Eye St., N.W., Washington, D.C. 20537 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: National Institute on Drug Abuse Rockville, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byToo Tranquil: The Epidemiology of An IdeaPatientization of the PopulationChemical Dependency Education within Medical Schools: Supervised Clinical Experience 1 December 1975Volume 83, Issue 6Page: 896-897KeywordsDrugs Issue Published: 1 December 1975 PDF downloadLoading ...
T-cell Subsets in Peripheral Blood and Tumors of Patients Treated With Oncolytic Adenoviruses
Authors: Taipale Kristian, Liikanen Ilkka, Juhila Juuso, Karioja-Kallio Aila, Oksanen Minna, Turkki Riku, Linder Nina, Lundin Johan, Ristimäki Ari, Kanerva Anna, Koski Anniina, Joensuu Timo, Vähä-Koskela Markus, Hemminki Akseli
Journal: Molecular Therapy (2015)

The quality of the antitumor immune response is decisive when developing new immunotherapies for cancer. Oncolytic adenoviruses cause a potent immunogenic stimulus and arming them with costimulatory molecules reshapes the immune response further. We evaluated peripheral blood T-cell subsets of 50 patients with refractory solid tumors undergoing treatment with oncolytic adenovirus. These data were compared to changes in antiviral and antitumor T cells, treatment efficacy, overall survival, and T-cell subsets in pre- and post-treatment tumor biopsies. Treatment caused a significant (P < 0.0001) shift in T-cell subsets in blood, characterized by a proportional increase of CD8(+) cells, and decrease of CD4(+) cells. Concomitant treatment with cyclophosphamide and temozolomide resulted in less CD4(+) decrease (P = 0.041) than cyclophosphamide only. Interestingly, we saw a correlation between T-cell changes in peripheral blood and the tumor site. This correlation was positive for CD8(+) and inverse for CD4(+) cells. These findings give insight to the interconnections between peripheral blood and tumor-infiltrating lymphocyte (TIL) populations regarding oncolytic virotherapy. In particular, our data suggest that induction of T-cell response is not sufficient for clinical response in the context of immunosuppressive tumors, and that peripheral blood T cells have a complicated and potentially misleading relationship with TILs.
Dock8 mutations cripple B cell immunological synapses, germinal centers and long-lived antibody production
Authors: Katrina L Randall, Teresa Lambe, Andy L Johnson, Bebhinn Treanor, Edyta Kucharska, Heather Domaschenz, Belinda Whittle, Lina E Tze, Anselm Enders, Tanya L Crockford, Tiphaine Bouriez-Jones, Duncan Alston, Jason G Cyster, Michael J Lenardo, Fabienne Mackay, Elissa K Deenick, Stuart G Tangye, Tyani D Chan, Tahra Camidge, Robert Brink, Carola G Vinuesa, Facundo D Batista, Richard J Cornall, Christopher C Goodnow
Journal: Nature Immunology (2009)
Platelet-activating factor: mediator of the third pathway of platelet aggregation? A study in three patients with deficient platelet-activating factor synthesis.
Authors: A Sturk, M C Schaap, J W ten Cate, H S Heymans, R B Schutgens, H Przyrembel, P Borst
Journal: Journal of Clinical Investigation (1987)

Thrombin, collagen, and Ca2+-ionophore A23187 aggregate platelets in the presence of inhibitors of the first (ADP-mediated) and second (cyclooxygenase-dependent) pathway of platelet activation. This aggregation, via a third pathway, was hypothesized to be mediated by the alkoxyether lipid platelet-activating factor (PAF). We recently demonstrated virtual absence of plasmalogen-type alkoxyether lipids and deficiency in key enzymes of their biosynthesis in Zellweger patients. We hypothesized that PAF synthesis might also be impaired. We report two Zellweger patients with an undetectable A23187-induced PAF synthesis of leukocytes (patients, less than 3 pmol PAF/10(8) granulocytes (PMN); four age-matched controls, 249-2,757 pmol PAF/10(8) PMN; five adult controls, 291-5,433 pmol PAF/10(8) PMN). In a third patient, residual PAF synthesis was detected. However in all patients the thrombin-induced third mechanism of platelet aggregation was present. We therefore conclude that PAF may not be the mediator of the third pathway.
Characterization of hepatitis C virus structural proteins with a recombinant baculovirus expression system
Authors: Henry H. Hsu, Mikhail Donets, Harry B. Greenberg, Stephen M. Feinstone
Journal: Hepatology (1993)

We cloned and expressed the sequences encoding the structural proteins of the hepatitis C virus in a baculovirus eukaryotic expression system. Four recombinant constructs expressed sufficient hepatitis C virus-specific proteins in insect cell culture to allow analysis of protein cleavage, glycosylation and immunoreactivity. Using immunoblot analysis, we detected a 22-kD protein corresponding to the hepatitis C virus capsid protein cleaved from a larger precursor. Recombinant constructs encoding the presumptive envelope (E1) protein produced products ranging from 30 to 35 kD, whereas constructs encoding the presumptive E2/NS1 protein expressed products ranging in size from 68 to 73 kD. The recombinant envelope proteins were glycosylated, as shown by sensitivity to endoglycosidase F digestion, whereas the capsid was not. We examined the immunoreactivity of these recombinant proteins using sera from 50 patients chronically infected with HCV. Forty-seven of 50 of these sera contained antibodies against the capsid, 14 (28%) also had antibodies against E1 and at least 5 (10%) had antibody against E2/NS1. Forty-seven of 50 sera (94%) were viremic, as determined on hepatitis C virus polymerase chain reaction. The three sera that were hepatitis C virus polymerase chain reaction negative did not have envelope antibodies, whereas all sera that had envelope antibodies were also hepatitis C virus polymerase chain reaction positive. Thus antibodies to baculovirus-expressed hepatitis C virus structural proteins, including E1 and E2/NS1, are found in the presence of viremia.
INCREASED CONTROL OF INSULIN COMA BY PRIOR ADMINISTRATION OF GLUCAGON : A PRELIMINARY COMMUNICATION
Authors: KARL T. DUSSIK, DONALD B. GIDDON, PETER D. WATSON, JOEL J. WHITE
Journal: American Journal of Psychiatry (1961)

We believe that the use of Glucagon for the arousal of patients from insulin coma and as a facilitating agent in the induction of insulin coma constitutes an important development in the modern treatment of schizophrenic psychoses, since it seems to render Sakel's treatment much easier to administer and contributes to its safety and economy.
Manipulation in Treatment of Low Back Pain
Authors: A. G. Boag
Journal: BMJ (1975)

associated with a rising haemoglobin level due to loss of plasma into the tissues or stimulation of erythropoiesis from renal caemia.Future investigations on the geographical distribution of edlampsia should therefore test the effects of a-ltitude and secondary polycythaemia.FinaUly, there is another aspect of low temperature and high humidity in the tropics -namely, tat such conditions may be associated with thunderstorms.The paper you quote from Colombia mentions that there are "no reports of electrically charged mountain winds" but does not give a quantitative record of thunder or lightning.Itt may not be entirely fortuitous that the first of nine eclamptic fits in a Germ-n woman on 21 June 1902 was -at the height of such a storm ("erster Anfall im Augenblick eines in der Ndhe niedergehenden schweren Blitzes").5Wihether from the cooling of an abnormal plasmna or the intense visual or auditory stimulation of an ischaemic cerebrum by a newby thunderbolt, the weather may stll give clues to the pathogenesis of eciampsia.-Iam, etc.,
Drinking Water Salinity and Maternal Health in Coastal Bangladesh: Implications of Climate Change
Authors: Aneire Ehmar Khan, Andrew Ireson, Sari Kovats, Sontosh Kumar Mojumder, Amirul Khusru, Atiq Rahman, Paolo Vineis
Journal: Environmental Health Perspectives (2011)

Background: Drinking water from natural sources in coastal Bangladesh has become contaminated by varying degrees of salinity due to saltwater intrusion from rising sea levels, cyclone and storm surges, and upstream withdrawal of freshwater.Objective: Our objective was to estimate salt intake from drinking water sources and examine environmental factors that may explain a seasonal excess of hypertension in pregnancy.Methods: Water salinity data (1998–2000) for Dacope, in rural coastal Bangladesh, were obtained from the Centre for Environment and Geographic Information System in Bangladesh. Information on drinking water sources, 24-hr urine samples, and blood pressure was obtained from 343 pregnant Dacope women during the dry season (October 2009 through March 2010). The hospital-based prevalence of hypertension in pregnancy was determined for 969 pregnant women (July 2008 through March 2010).Results: Average estimated sodium intakes from drinking water ranged from 5 to 16 g/day in the dry season, compared with 0.6–1.2 g/day in the rainy season. Average daily sodium excretion in urine was 3.4 g/day (range, 0.4–7.7 g/day). Women who drank shallow tube-well water were more likely to have urine sodium &gt; 100 mmol/day than women who drank rainwater [odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.11–3.80]. The annual hospital prevalence of hypertension in pregnancy was higher in the dry season (OR = 12.2%; 95% CI, 9.5–14.8) than in the rainy season (OR = 5.1%; 95% CI, 2.91–7.26).Conclusions: The estimated salt intake from drinking water in this population exceeded recommended limits. The problem of saline intrusion into drinking water has multiple causes and is likely to be exacerbated by climate change–induced sea-level rise.
Marital state, alcohol consumption, and liability to myocardial infarction, stroke, diabetes mellitus, or hypertension in men from Gothenburg.
Authors: B Lindegard, M J Langman
Journal: BMJ (1985)

Data from the Swedish personal number system were used to examine rates of admissions to hospital, particularly with myocardial infarction, stroke, diabetes mellitus, or hypertension, in relation to marital state and histories of admission with alcoholism in 77843 men from Gothenburg born in 1911-40. The number of admissions to hospital with the four diseases varied with marital state and history of admission with alcoholism, but by considering each subset from the total group it was possible to show that among alcoholic men no material variation in the number of admissions was evident. By contrast, among the non-alcoholic men those who were married were particularly prone to myocardial infarction but less likely to be admitted with stroke or diabetes mellitus than the unmarried or divorced men. The data show the value of common personal and health statistical numbering systems in generating epidemiological information beyond that obtainable from aggregated data without a record linkage technique.