tbuckley/cabot-search huggingface dataset:
Endogenous Retroviral env Expression in Primary Murine Leukemias: Lack of Xenotropic Antigens but Presence of Distinct Mink Cell Focus-Forming env Subtypes Correlating With Ecotropic Virus Inoculated and Mouse Strain
Authors: Miles W. Cloyd, Leonard H. Evans
Journal: JNCI Journal of the National Cancer Institute (1987)

The expression of endogenous retroviral env products on primary leukemia cells of mice was studied with the use of a panel of monoclonal antibodies that discriminate between the various classes of murine leukemia viruses [MuLVs; ecotropic, xenotropic, and mink cell focus-forming (MCF)], as well as between various subtypes within each class. Most spontaneous AKR or Friend MuLV (F-MuLV)- or Moloney MuLV (M-MuLV)-induced AKR or NFS mouse leukemia cells expressed no xenotropic viral envelope antigens but always expressed MCF proteins. Spontaneous C58 lymphomas, on the other hand, often expressed xenotropic proteins in addition to MCF proteins. The subtype of MCF envelope antigens present on leukemia cells, as well as on isolated MCF viruses, varied in a reproducible manner, depending on the mouse strain inoculated and the ecotropic virus used (F-MuLV or M-MuLV). Specifically, F-MuLV consistently induced certain type(s) of MCF envelope antigens on leukemia cells of NFS mice, whereas M-MuLV induced different ones. Similar antigenic patterns were found on the MCF viruses isolated from these mice. Furthermore, MCF envelope antigens (on viruses or leukemia cells) induced in NFS mice by M-MuLV differed from those induced in AKR mice. This finding demonstrated a mouse strain influence on the endogenous MCF env sequences expressed following infection by a given ecotropic virus. The endogenous MCF env sequences in mice thus appear to be a set of genes highly expressed during leukemogenesis, with particular ones specifically expressed in a given mouse strain infected with a given ecotropic virus.
Routine X-Rays in Nasal Trauma: The Influence of Audit on Clinical Practice
Authors: J F Sharp, S Denholm
Journal: Journal of the Royal Society of Medicine (1994)

The introduction of treatment protocols require audited prospective data. The use of X-rays in patients with simple nasal trauma is common but of limited value. A prospective audit of this practice and the implications of introducing a 'no X-ray' policy for these patients into the local casualty department are presented. Patients are spared radiation exposure and there are savings in patient throughput time and departmental costs. Casualty departments which have not already adopted such a policy are urged to do so. Where such a protocol is in use, audit to ensure adherence is encouraged.
A detailed immunohistochemical analysis of PI3K/AKT/MTOR pathway in lung cancer: Correlation with PIK3CA, AKT1, K-RAS or PTEN mutational status and clinicopathological features
Authors: E. Trigka, G. Hardavella, A. Saetta, N. Kavantzas, P. Korkolopoulou, N. Anastasiou, E. Patsouris
Journal: European Respiratory Journal (2013)

Objectives :1)To search for any relation between the mutational status of tPIK3CA,K-RAS,AKT-1 and PTEN and expressions of p85a and p110γ subunits of PI3K, phosphorylated (-)AKT,p-mTOR,PTEN,PP79S6K and p-4E-BP1 in non small cell lung cancer(NSLC).2)To correlated them with clinicopathological parameters.   Methods: Retrospective study in 102 NSCLC patients.Expression of phosphorylated (p-)mTOR,p-AKT,p85a and p110γ subunits of PI3K,p-p70S6K, PTEN,p-4E-BP1 was studied by immunohistochemistry in 102 lung specimens. and correlation with clinicopathological features. Also 61 cases were tested for PIK3CA, AKT-1, PTEN and K-RAS mutations.   Results: Patients were 14 females and 88 males(mean age 71years).18.5% of cases had a K-RAS mutation at codon 12, 5 had PTEN mutation(exon 7,8) and 1 had AKT-1 mutation (p.E17K). PTEN mutations were correlated with nodal metastasis. p-mTOR and p110γPI3K expressions were higher in adenocarcinomas and p-4E-BP1 in squamous carcinomas. An inverse correlation was noted between p-4E-BP1 immunoexpressin and tumour status and and nuclear p-AKT expression regarding stage. p-4E-BP1 expression single or combined with cytoplasmic p-AKT expression had an adverse prognostic significance in adenocarcinomas (univariate survival analysis).   Conclusions: Alterations of PI3K/AKT/mTOR pathway are differentially implicated in the pathogenesis and aggressivess of NSCLC. Nuclear p-4E-BP1 immunoexpression seems to be a prognostic molecular marker in adenocarcinomas especially when combined with p-AKT. Careful evaluation of these parameters may predict tumours most sensitive to PI3K/AKT signalling inhibitors.
Phase I and Pharmacologic Study of Oral (PEG-1000) 9-Aminocamptothecin in Adult Patients With Solid Tumors
Authors: Maja J.A. de Jonge, Cornelis J.A. Punt, A. Hans Gelderblom, Walter J. Loos, Vera van Beurden, André S.Th. Planting, Maria E.L. van der Burg, Lydia W.G.M. van Maanen, Brian K. Dallaire, Jaap Verweij, D.J. Theo Wagener, Alex Sparreboom
Journal: Journal of Clinical Oncology (1999)

9-Amino-20(S)-camptothecin (9-AC) is a specific inhibitor of topoisomerase-I. Recently, a bioavailability of approximately 48% for the oral PEG-1000 formulation was reported. We conducted a phase I and pharmacokinetic study of the oral PEG-1000 formulation of 9-AC to define the maximum-tolerated dose, toxicity profiles, pharmacokinetic-dynamic relationships, and preliminary antitumor activity in patients with solid tumors.Patients were treated with oral (PEG-1000) 9-AC given once a day for 7 or 14 days at doses ranging from 0.25 to 1.1 mg/m(2)/d; cycles were repeated every 21 days. For pharmacokinetic analysis, plasma sampling was performed on days 1 and 6 or 8 of the first course using a validated high-performance liquid chromatographic assay.Thirty patients were entered onto the study; three patients were not assessable for toxicity and response. Twenty-seven patients received a total of 89 courses. The dose-limiting toxicities (DLTs) were myelosuppression and diarrhea at a dose of 1.1 mg/m(2)/d for 14 days. Pharmacokinetics showed a substantial interpatient variation of the area under the plasma concentration-time curve (AUC) of 9-AC. The intrapatient variability was extremely small. A significant correlation was observed between the percentage decrease in WBC count and the AUC of 9-AC lactone (r(2) = 0.86). One partial response was noted in a patient with metastatic colorectal cancer.DLTs in this phase I study of oral 9-AC daily for 14 days every 21 days were myelosuppression and diarrhea. The recommended dose for phase II studies is 0.84 mg/m(2)/d. In view of the substantial interpatient variability in AUC and the availability of a limited sampling model, a pharmacokinetic guided phase II study should be considered.
Relapsed hydatid disease of lungs
Authors: Bahrom Amanov, Davlathon Maksumov, Rustem Hayaliev
Journal: European Respiratory Journal (2013)

The surgical treatment of hydatid disease of lungs is unique and the most radical, however and after operations the development of relapses is possible. On the data of the literature the relapse of hydatid disease after surgical treatment does not tend to decrease and changes from 4% up to 48%.  In the department of surgery of lungs and mediastinum Republican Specialized Center of Surgery named after acad. V.Vahidov from 1975 to 2012yy there were on treatment 2762 patients with hydatid disease of lungs. From 2762 operated patients concerning the various forms of hydatid disease of lungs relapse of disease from 1 to 7 years we observed in 178 (6,44%) patients. From them: men - 103 (57,9%), women - 75 (42,1%). The age of the patients varied from 9 to 72 years. From 178 patients 147 (82,58%) undergone operations, not operated 31 (17,41%) - the reason was disseminated process, wide distribution of hydatid cysts. 140 (95,23%) patients were performed organsaving operation, 7 (4,77%) patients underwent resections.  In the postoperative period albendazole was administered in a doze 10-12 mg/kg/day, quantity of courses depended on the form of a defeat. Using preventive chemotherapy realistically reduces the risk of the development of the relapse of hydatid disease, hereunder, rescuing patient from the repeated operations and possible complications.
10-minute consultation: Removal of ear wax
Authors: T Aung
Journal: BMJ (2002)

This is part of a series of occasional articles on common problems in primary care An elderly man says he cannot hear properly and the problem has been worsening for a few months. He now has difficulty conversing and watches television at high volume. Normally, he is a sociable man, so he is frustrated and depressed. You find that both external ear canals are occluded with hard wax, which you offer to remove. Prevalence— Explain that impacted ear wax is common; just under a third of older people experience the problem. In the United Kingdom thousands of people every week have ear wax removed. The chances of wax accumulating are increased by use of hearing aids and cotton buds. ### Evidence of complications
The Effects of Coffee on Serum Lipids and Blood Pressure in a UK Population
Authors: Tim Lancaster, John Muir, Christopher Silagy
Journal: Journal of the Royal Society of Medicine (1994)

Data on coffee consumption were collected for 1074 adults attending for health checks in the OXCHECK study, to assess associations with serum lipids and blood pressure. Of the sample, 70.5% drank coffee, largely instant. Coffee had no significant effects on total or high-density lipoprotein (HDL) cholesterol or blood pressure, and was negatively correlated with serum triglycerides. The type of coffee drunk in the UK does not adversely effect these cardiovascular risk factors.
Final results of a pharmacokinetic (PK) and pharmacodynamic (PD) phase I trial of ARQ 197 incorporating dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) studies investigating the antiangiogenic activity of selective c-Met inhibition
Authors: T. A. Yap, S. Frentzas, N. Tunariu, J. Barriuso, D. Harris, M. Germuska, C. Waghorne, J. Li, N. deSouza, J. S. de Bono
Journal: Journal of Clinical Oncology (2009)

3523 Background: ARQ 197 (ARQ) is a selective non-ATP competitive inhibitor of c-Met, a receptor tyrosine kinase implicated in tumor cell proliferation, invasion and angiogenesis. Preclinical data and declines in circulating endothelial cell (CEC) levels in patients (pts) receiving ARQ suggest antiangiogenic potential of c-Met inhibition. Methods: ARQ was administered orally twice daily (bid) to pts with advanced solid tumors. Pre and post-therapy tumor biopsies were mandated for c-Met and FAK immunohistochemical studies during dose escalation (n = 16). CEC enumeration was evaluated. 12 pts are being investigated in the maximum tolerated dose (MTD) expansion cohort with DCE and Diffusion Weighted (DW) MRI. Results: 29 pts (14 F/15 M; mean 54.4 yrs) received ARQ at doses of 100 (n = 3), 200 (n = 6), 300 (n = 16), and 400 (n = 4) mg bid. 3 pts experienced dose limiting toxicities of CTCAEv3 grade (G)3 fatigue (200 mg bid); G3 hand-foot syndrome, G3 mucositis and G3 febrile neutropenia (400 mg bid). This established the ARQ MTD/recommended phase II dose (RP2D) at 300 mg bid. Other toxicities were G1–2, such as fatigue (n = 5); diarrhea, nausea and vomiting (n = 3). Mean AUC 0–12h and C max increased linearly through the MTD. Statistically significant post-ARQ inhibition of high baseline phosphorylated c-Met and FAK expression in tumor tissue was seen in all dose cohorts confirming target inhibition. Disease stabilization (SD) was seen in 11 pts for up to 23 weeks with tumor regressions up to 12.4%. 13 of 20 pts had post-ARQ CEC declines of up to 100%. In the DCE-MRI cohort to date, preliminary analyses of k trans histograms from pelvic lesions were consistent with antiangiogenic effects, with a k trans median reduction of 20.1% on day 7 of ARQ (intrapatient baseline variability: 2.8%). This effect was still present (k trans median decline: 8.3%) on day 56 of ARQ. Conclusions: ARQ is well tolerated with MTD/RP2D of 300mg bid, linear PK and evidence of phosphorylated c-Met and FAK inhibition. CEC and preliminary DCE-MRI data support the antiangiogenic effects of c-Met inhibition with ARQ. Correlation with other DCE parameters and DW changes will be presented. [Table: see text]
Acute heart failure in patients with acute aortic syndrome: pathophysiology and clinical–prognostic implications
Authors: Fabio Vagnarelli, Anna Corsini, Massimiliano Lorenzini, Davide Pacini, Marinella Ferlito, Letizia Bacchi Reggiani, Simone Longhi, Samuele Nanni, Giulia Norscini, Laura Cinti, Giulia Bugani, Ferdinando Pasquale, Elena Biagini, Francesco Grigioni, Roberto Di Bartolomeo, Marco Marini, Gian Piero Perna, Giovanni Melandri, Claudio Rapezzi
Journal: European Journal of Heart Failure (2015)
Childhood asthma control test: Validation of the Arabic Tunisian dialect version in 51 patients
Authors: Hanadi Ouali, Makram Zneidi, Anissa Berraiss, Boutheina Ben Safta, Jamel Ammar, Amira Sellami, Samir Ennigrou, Agnès Hamzaoui
Journal: European Respiratory Journal (2012)

Childhood Asthma Control Test or c-ACT was translated in different languages. We propose to validate the Arabic Tunisian dialect version by checking both it9s understood by patients and their parents and the conformity with the control criteria of international recommendations. Cross-sectional study was conducted in 51 asthmatic children, aged from 4 to 11 years, followed for at least 6 months. c-ACT was administrated before consultation. The level of asthma control was compared to that estimated by the expert based on GINA criteria with an evaluation period of 4 weeks. Understanding of this Arabic version has been confirmed with the patients and their parents.This version showed a satisfactory internal consistency with Cronbach9s alpha equal to 0.853. The area under the ROC curve equal to 0.993 is highly significant (p
Management of chemotherapy‐induced anemia (CIA) with biosimilar epoetin alfa (Binocrit) in patients with pancreatic cancer (PC): An interim analysis of an ongoing French national observational study (The OncoBOS study).
Authors: Jean Philippe Metges, Jérôme Desramé, Vincent Bourgeois, Otilia Stamerra, Jean-Loup Mouysset, Camille Aubron-Olivier, Domitille Fernet, Gilles Boschetti
Journal: Journal of Clinical Oncology (2015)

479 Background: OncoBOS is a prospective, non-interventional study describing Binocrit use in routine practice in France in patients receiving chemotherapy treatment (CT) for solid tumors, lymphoma or myeloma. This interim sub-analysis focuses on patients with PC. Methods: Patients ≥18 years with PC, CIA and eligible for treatment with Binocrit were included in this analysis. Patients characteristics, data on CIA and its management and predominant factors considered by the physician in prescribing Binocrit were recorded at baseline (BL), 3-4 weeks and 12 (± 1) weeks later. Hemoglobin (Hb) outcomes assessed included the proportion of patients achieving a Hb increase ≥1 and ≥2 g/dL, and the mean Hb change from BL. Results: 59 patients with PC (32 females (54.2%), mean age 68.3 years) from 22 sites were recruited from September 2011 to April 2014. Mean and median BL Hb levels were both 10 g/dL. The mean increase in Hb level was 1.1 g/dL after 1 month and 1.2 g/dL after 3 months (p&lt;0.001 vs BL) of Binocrit treatment. A Hb increase ≥1 g/dL was achieved by 48.3% of patients at week 3-4 and 54.2% at week 12; a Hb increase ≥2 g/dL was achieved by 25.9% and 35.4% of patients at the same time points. Patients received a median dose of 30,000 IU Binocrit once weekly. Three of the 59 patients (5.1%) required a dose increase. Transfusion rates remained stable at 11.9% and 15.1% at week 3-4 and week 12, respectively. Oral and intravenous (IV) iron supplementation rates were low: oral iron was received by 1.7% and 0% of patients at week 3-4 and week 12, respectively; 20.3% and 13.2% of patients received IV supplementation at the same time points. Of note, iron status was assessed in only 11.9% of subjects at BL. Physicians considered quality of life (37.3%), fatigue (25.4%) and avoidance of blood transfusion (10.2%) as predominant factors in the rationale for CIA management. Over the treatment period, three treatment-related adverse reactions (non-serious) were recorded. Conclusions: This sub-analysis indicates that Binocrit, used in routine practice, is effective and well tolerated for the treatment of CIA in patients with PC.
Psoriasis and cardiovascular disease: an association or a reason to treat?
Authors: D.J. Margolis
Journal: British Journal of Dermatology (2011)

Conflicts of interest None declared. Worldwide psoriasis is a common systemic inflammatory illness. The majority of recent studies have shown an association between psoriasis and coronary artery disease (CAD).1 2–3 It has been hypothesized that the association between psoriasis and CAD is due to chronic systemic inflammation.1, 3 As a risk factor for CAD, psoriasis represents a disease that could potentially be modified, thereby decreasing the risk of morbidity and mortality due to CAD, a very important public health concern.3 In fact, this should be a directly testable hypothesis, which as a question is ‘Does the aggressive treatment of psoriasis prevent CAD?’. The study by Abuabara et al.4 attempted to answer this question. This well‐conducted study published in this issue of the BJD evaluated more than 25 000 individuals with psoriasis who are at highest risk for CAD – those with severe to moderate disease.4 They conducted this study using administrative claims data from a very large healthcare insurance programme. They basically compared two broad classes of therapy: those receiving light therapy and those receiving systemic agents such as ‘biologics’, methotrexate and ciclosporin.4 They assumed that the systemic therapies would have a greater effect on the systemic inflammatory components of psoriasis. While it is up to the reader to review this study comprehensively, overall they did not find a decreased risk of myocardial infarction in those treated with systemic agents compared with those who received light therapy. A more nuanced view might be that there was a trend toward an overall 30%increase among systemic therapy users and about a 30%decrease in a subset of those at highest risk of CAD, those aged < 50 years.4
Medical oncology manpower training: a position statement of the American Society of Clinical Oncology.
Authors: B J Kennedy, P Calabresi, B Clarkson, E Frenkel
Journal: Journal of Clinical Oncology (1986)

The evolution of Medical Oncology is facing its first major crisis, that of oversupply of trained oncologists. The tabulated number of certified medical oncologists does not constitute all of the physicians practicing Medical Oncology in the United States. Because of the adequate supply of medical oncologists in clinical practice, but a deficiency of academic oncologists dedicated to research careers, a reduction in training programs should emphasize those programs that lack research opportunities. These recommendations are in keeping with the report of the Long-Range Planning Committee of the American Society of Clinical Oncology of March 21, 1984. Plans to expedite these goals are being established.
Lung Tumorigenesis in Mice After Chronic Exposure in Early Life to a Low Dose of Dimethylnitrosamine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lucy M. Anderson, Loretta J. Priest, John M. Budinger
Journal: JNCI Journal of the National Cancer Institute (1979)

Strain A female mice were exposed to 10 ppb dimethylnitrosamine (DMN) in their drinking water for 4 weeks before mating. Treatment was continued through pregnancy and lactation and after weaning until the progeny were 22 weeks old. The incidence of primary lung tumors among the treated progeny (23%) was significantly higher (P less than 0.021) than that among controls (8%). The effect of the DMN was greatest among the males: 32% had lung tumors, compared with 4% of the control males (P less than 0.016). The DMN-exposed females also had a higher lung tumor incidence than did the controls, but the difference was not of statistical significance. These results demonstrate carcinogenicity of DMN at a dose approaching amounts possibly encountered by the human population as a result of environmental exposure.
Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease
Authors: Paul S. Bernstein, Binxing Li, Preejith P. Vachali, Aruna Gorusupudi, Rajalekshmy Shyam, Bradley S. Henriksen, John M. Nolan
Journal: Progress in Retinal and Eye Research (2015)
Flow cytometric assay for direct quantification of neutrophil extracellular traps in blood samples
Authors: Mathilde Gavillet, Kimberly Martinod, Raffaele Renella, Chad Harris, Nate I. Shapiro, Denisa D. Wagner, David A. Williams
Journal: American Journal of Hematology (2015)

Neutrophil extracellular traps (NETs) contribute to innate immunity as well as numerous diseases processes such as deep vein thrombosis, myocardial ischemia, and autoimmune disease. To date, most knowledge on NETs formation has been gathered via the qualitative microscopic examination of individual neutrophils in vitro , or aggregate structures in vivo . Here we describe a novel flow cytometry (FLOW)‐based assay to identify and quantify NETs using antibodies against key NETs constituents, specifically DNA, modified histones, and granular enzymes. This method is applicable to both murine and human samples for the assessment of induced NETs in vitro, or detection of NETosis in vivo in blood samples. This FLOW‐based method was validated by comparison with the well‐established microscopy assay using two genetic mouse models previously demonstrated to show defective NETosis. It was then used on healthy human neutrophils for detection of ex vivo induced NETs and on blood samples from patients with sepsis for direct assessment of in vivo NET‐forming neutrophils. This new methodology allows rapid and robust assessment of several thousand cells per sample and is independent of potential observer‐bias, the two main limitations of the microscopic quantification. Using this new technology facilitates the direct detection of in vivo circulating NETs in blood samples and purification of NETting neutrophils by fluorescence‐activated cell sorting (FACS) for further analysis. Am. J. Hematol. 90:1155–1158, 2015. © 2015 Wiley Periodicals, Inc.
Births at Christmas are different: population based survey of 2 million deliveries
Authors: M. Melbye, J. Wohlfahrt, T. Westergaard, A. K. V. Jensen, A. Koch, H. Hjalgrim, A. Kristensen, P. Aaby
Journal: BMJ (1997)

communication).This allowance is paid to five categories of patients, including people who have difficulty in walking. 8 A person is eligible for this allowance on the basis of a self assessment questionnaire. 9We thank the patients and consultants who participated, and Noor and Sana Sharrack for their help in measuring some of the study distances.