tbuckley/cabot-search huggingface dataset:
The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C
Authors: Stefan Zeuzem, Peter Buggisch, Kosh Agarwal, Patrick Marcellin, Daniel Sereni, Hartwig Klinker, Christophe Moreno, Jean-Pierre Zarski, Yves Horsmans, Hongmei Mo, Sarah Arterburn, Steven Knox, David Oldach, John G. McHutchison, Michael P. Manns, Graham R. Foster
Journal: Hepatology (2011)

Tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitor, individually have activity against hepatitis C virus (HCV) genotype 1. The antiviral activity of tegobuvir and GS-9256 as oral combination therapy, or together with ribavirin (RBV) or pegylated interferon (Peg-IFN) alpha-2a and RBV, was assessed in a phase II, randomized, open-label trial. Treatment-naïve patients with genotype 1 HCV were assigned 28 days of tegobuvir 40 mg twice-daily (BID) and GS-9256 75 mg BID (n = 16), tegobuvir and GS-9256 plus RBV 1,000-1,200 mg daily (n = 15), or tegobuvir and GS-9256 plus Peg-IFN alpha-2a (180 μg once-weekly)/RBV (n = 15). The primary efficacy endpoint was rapid virologic response (RVR), with HCV RNA <25 IU/mL at day 28. After 28 days, all patients received Peg-IFN/RBV. All patients with viral rebound or nonresponse, defined as >0.5-log(10) increase in HCV RNA from nadir or <2-log decrease at day 5, initiated Peg-IFN/RBV immediately. Median maximal reductions in HCV RNA were -4.1 log(10) IU/mL for tegobuvir/GS-9256, -5.1 log(10) IU/mL for tegobuvir/GS-9256/RBV, and -5.7 log(10) IU/mL for tegobuvir/9256/Peg-IFN/RBV. RVR was observed in 7% (1 of 15) of patients receiving tegobuvir/GS-9256, 38% (5 of 13) receiving tegobuvir/GS-9256/RBV, and 100% (14 of 14) receiving tegobuvir/9256/PEG-IFN/RBV. The addition of Peg-IFN/RBV at day 28 or earlier resulted in HCV RNA <25 IU/mL at week 24 in 67% (10 of 15), 100% (13 of 13), and 94% (13 of 14) of patients in the three treatment groups. Transient elevations in serum bilirubin occurred in all treatment groups.In genotype 1 HCV, adding RBV or RBV with Peg-IFN provides additive antiviral activity to combination therapy with tegobuvir and GS-9256.
Abstract 5031: Combination inhibition of the FAK-p53 and MDM2-p53 interactions suppressed proliferation in mesothelioma
Authors: Wenbin Ou, Jonathan A. Fletcher
Journal: Cancer Research (2010)

Abstract Mesothelioma is a chemotherapy-resistant neoplasm, as is evident in the dismal survival for patients with this asbestos-associated disease. Conventional chemotherapies and radiation therapy have only limited efficacy, and improved survival will require development of novel and more effective pharmacological interventions. Although p53 genomic mutations are uncommon in mesothelioma, we hypothesized that functional p53 inactivation (resulting from NF2-dysregulated FAK activation) might be a frequent event. Using proteomic methods, with tandem mass spectrometry analyses of mesotheliomas after double immuno-affinity purifications for p53 and phosphotyrosine, we find that FAK is consitutively activated in 10 of 10 mesothelioma cell lines and 9 of 9 mesothelioma surgical specimens, and associated with p53 in 6 of 6 mesothelioma cell lines. In four mesotheliomas with non-mutant p53, FAK silencing by lentiviral short hairpin RNA (shRNA) induced expression and phosphorylation of p53 at Ser15. However, FAK regulation of mesothelioma proliferation was not restricted to p53-dependent pathways, as demonstrated by immunoblots after FAK knockdown in JMN1B mesothelioma cells, which have mutant/inactivated p53, compared to MESO924, MESO257, MESO296, and MESO428 cells, which have nonmutant p53. Additive effects were obtained through a coordinated attack on p53, as demonstrated by immunoblots, cell viability and cell cycle analyses, showing that FAK knockdown and MDM2 inhibition (nutlin-3) induced greater p53 expression, cell apoptosis, anti-proliferative effects and cell cycle arrest, compared to either intervention alone. These findings highlight novel therapeutic opportunities in mesothelioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5031.
Wide Complex Tachycardia
Authors: ROBERT BADGETT
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 October 1986Wide Complex TachycardiaROBERT BADGETT, M.D.ROBERT BADGETT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-4-623_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Both the difficulty of accurately diagnosing the cause of wide complex tachycardia and the consequences of misdiagnosis were well shown in the recent article by Stewart and colleagues ( 1 ).In the past, many bedside clues have been advanced to aid in the differentiation of the cause, but study has shown only electrical evidence of atrioventricular dissociation to be reliable. Forty-five (1) to sixty-eight (2) percent of episodes of wide complex tachycardia of ventricular origin have yielded electrical evidence of atrioventricular dissociation on retrospective study. Two pressing questions are pertinent to the immediate bedside diagnosis: What...References1. STEWARTBARDYGREENE RGH. Wide complex tachycardia: misdiagnosis and outcome after emergent therapy. Ann Intern Med. 1986;104:766-71. LinkGoogle Scholar2. WELLENSBäRLIE HFK. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am J Med. 1978;64:27-33. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Moses Cone Hospital Greensboro, NC 27420 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1986Volume 105, Issue 4Page: 623-624KeywordsRetrospective studiesTachycardia Issue Published: 1 October 1986 PDF downloadLoading ...
Evidence based medicine: does it make a difference?
Authors: Alireza Moayyeri, Akbar Soltani
Journal: BMJ (2005)

Evidence based medicine: does it make a difference? Use wiselyEditor-The term "evidence based medicine" entered the scientific lexicon only a little more than a decade ago. 1 What caused its remarkable spread, and what are the implications of its broad and rapid diffusion?The team that coined the term at first considered using the phrase "scientific medicine" but rejected it because it implied that other approaches were by definition unscientific. 2However, critics have argued that the term evidence based medicine carries a similar moral valence and linguistic slipperiness. 3 Who could argue against the notion of providing care that integrates individual clinical skill and the best external evidence? 4 Originally developed as a method for teaching medical residents, evidence based medicine is being applied ever more broadly to the organisation and delivery of medical services.Multiple stakeholders now seek to assume its mantle for purposes that often contradict its original intent.Managers, equating lack of evidence with lack of effectiveness, use it as a rationale for cutting services.Industry generates evidence of questionable quality to promote its products.Medical researchers come to believe that they hold a monopoly on generating and interpreting evidence.Evidence based medicine, developed as a means of taming the unscientific and messy world of clinical practice, has itself entered the unscientific and messy world of politics. 5ike any technology, evidence based medicine carries risks and benefits and can be used appropriately or inappropriately.Overly inclusive definitions threaten to deprive the term of meaning, and unchecked use increases the risk of misuse.In the past decade, evidence based medicine has contributed much to how we teach, deliver, and think about clinical services.In the coming decade, we must continue to ensure that it is not only used widely but wisely.
I787 provides signals for c-Kit receptor internalization and functionality that control mast cell survival and development
Authors: Zane Orinska, Niko Föger, Michael Huber, Julia Marschall, Farhad Mirghomizadeh, Xin Du, Marina Scheller, Philip Rosenstiel, Torsten Goldmann, Annalena Bollinger, Bruce A. Beutler, Silvia Bulfone-Paus
Journal: Blood (2010)
Transcriptional Profiling Identifies Cyclin D1 as a Critical Downstream Effector of Mutant Epidermal Growth Factor Receptor Signaling
Authors: Susumu Kobayashi, Takeshi Shimamura, Stefano Monti, Ulrich Steidl, Christopher J. Hetherington, April M. Lowell, Todd Golub, Matthew Meyerson, Daniel G. Tenen, Geoffrey I. Shapiro, Balázs Halmos
Journal: Cancer Research (2006)

Abstract Activating mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain determine responsiveness to EGFR tyrosine kinase inhibitors in patients with advanced non–small cell lung cancer (NSCLC). The modulation of transcriptional pathways by mutant EGFR signaling is not fully understood. Previously, we and others identified a single base pair change leading to a threonine to methionine (T790M) amino acid alteration in the ATP-binding pocket of the EGFR as a common mechanism of acquired resistance. The gefitinib-resistant, T790M-mutant H1975 NSCLC cell line undergoes prominent growth arrest and apoptosis when treated with the irreversible EGFR inhibitor, CL-387,785. We did a transcriptional profiling study of mutant EGFR target genes that are differentially expressed in the “resistant” gefitinib-treated and the “sensitive” CL387,785-treated H1975 cells to identify the pivotal transcriptional changes in NSCLC with EGFR-activating mutations. We identified a small subset of early gene changes, including significant reduction of cyclin D1 as a result of EGFR inhibition by CL-387,785 but not by gefitinib. The reduction in cyclin D1 transcription was associated with subsequent suppression of E2F-responsive genes, consistent with proliferation arrest. Furthermore, cyclin D1 expression was higher in EGFR-mutant lung cancer cells compared with cells with wild-type EGFR. EGFR-mutant cells were routinely sensitive to the cyclin-dependent kinase inhibitor flavopiridol, confirming the functional relevance of the cyclin D axis. These studies suggest that cyclin D1 may contribute to the emergence of EGFR-driven tumorigenesis and can be an alternative target of therapy. (Cancer Res 2006; 66(23): 11389-98)
Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia
Authors: A Ruggeri, M Labopin, G Sanz, S Piemontese, W Arcese, A Bacigalupo, D Blaise, A Bosi, H Huang, D Karakasis, Y Koc, M Michallet, A Picardi, J Sanz, S Santarone, H Sengelov, J Sierra, L Vincent, F Volt, A Nagler, E Gluckman, F Ciceri, V Rocha, M Mohty
Journal: Leukemia (2015)
Some Quantitative Aspects of Nitrogen Retention with Norethandrolone
Authors: Howard G. Greene, Harold Blumberg, William Metcalf
Journal: JAMA (1963)

THE METABOLIC DATA reported in studies on the nitrogen-retaining effects of natural and synthetic anabolic steroids do not lend themselves easily to quantitative comparison. The effect of the anabolic agents in nitrogen metabolism is variously reported as a rate, grams positive nitrogen balance per day (grams retained per day), grams retained per period, or as milligrams of nitrogen retained per kilogram body weight per day.<sup>1-3</sup>The studies in which nitrogen retention is reported in milligrams per kilogram of body weight per day cannot be compared to those in which the rates are reported as grams retained or grams balance per day, unless the weight of the patient is included in the data. Unfortunately, this information is often omitted.<sup>1,4,5</sup>Comparisons between individual trials in a given series are also very difficult to make. Regardless of which rate expression is used, the range of values is usually
Swine flu has been "considerably less lethal than feared," says Donaldson
Authors: O. Mashta
Journal: BMJ (2009)

Two thirds of primary care trusts in England have now reached agreements for GPs to vaccinate children between the ages of 6 months and 5 years against swine flu and the rest are close to finalising deals.

Speaking at the weekly press briefing on swine flu, Ian Dalton, national director for the NHS flu resilience, said that immunisation of the under 5s had started opportunistically where deals were in place.

The estimated number of swine flu cases throughout the country has reduced substantially as the second peak of the pandemic seems …
Prospective evaluation of ERCP performance: results of a nationwide quality registry
Authors: Vivian Ekkelenkamp, Robert de Man, Frank ter Borg, Pieter Borg, Marco Bruno, Marcel Groenen, Bettina Hansen, Antonie van Tilburg, Erik Rauws, Arjun Koch
Journal: Endoscopy (2015)

<b>Background and study aims: </b>Despite significant interest from health care authorities, patient organizations, and insurance companies, data on procedural outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in general and academic practice are sparse. The aims of this study were to assess procedural outcome of ERCP within a large prospective registry in The Netherlands, and to evaluate associations between endoscopist-related factors and procedural outcome. <b>Methods: </b>All endoscopists performing ERCP in The Netherlands were invited to register their ERCPs over a 1-year period using the Rotterdam Assessment Form for ERCP (RAF-E). The primary outcome measure was procedural success. A priori difficulty level of the procedure was classified according to Schutz. Baseline characteristics of the endoscopist (e. g. previous experience) were recorded at study entry. Regression analysis was performed to identify predictors of procedural outcome. <b>Results: </b>A total of 8575 ERCPs were registered by 171 endoscopists from 61 centers, constituting about 50 % of all ERCPs performed nationally during the study period. Overall procedural success was 85.8 %. Intact papillary anatomy was present in 5106 patients (59.5 %): procedural success in this subgroup of patients was 83.4 % vs. 89.4 % after sphincterotomy (<i>P</i> < 0.001). Multivariate logistic regression identified "degree of difficulty," "intact papillary anatomy," and "previous ERCP failure" to be independently associated with procedural failure. "Yearly volume of ERCPs" and "trainee involvement" were independently associated with success. <b>Conclusions: </b>The nationwide prospective RAF-E registry proved to be a valuable tool to gain insight into procedural outcome of ERCPs.
Morning Levels of C-Reactive Protein in Children with Obstructive Sleep-disordered Breathing
Authors: Athanasios G. Kaditis, Emmanouel I. Alexopoulos, Efthimia Kalampouka, Eleni Kostadima, Anastasios Germenis, Elias Zintzaras, Konstantinos Gourgoulianis
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Obstructive sleep-disordered breathing is associated with cardiovascular disease in adults, and elevated C-reactive protein (CRP) has been proposed as a link between the two disorders. We hypothesized that children with sleep-disordered breathing have higher CRP values than do control subjects. CRP was measured in 39 children (mean age +/- SD: 6.9 +/- 3.2 years) without snoring (controls) and in 102 children (6.2 +/- 2.2 years) with habitual snoring who underwent polysomnography. No significant differences were found in mean CRP values between control subjects (0.12 +/- 0.16 mg/dl; n = 39) and snorers with an apnea-hypopnea index of less than 1 episode/hour (0.15 +/- 0.26; n = 18), snorers with an index of 1 or more and less than 5 (0.15 +/- 0.26; n = 54), and snorers with an index of 5 or more (0.22 +/- 0.43; n = 30; p > 0.05). There was no correlation between CRP or log-transformed CRP values and apnea-hypopnea index, respiratory movement/arousal index, Sa(O(2)) nadir, oxygen desaturation (>/= 4%) of hemoglobin index, or percentage of sleep time with saturation less than 95% (p > 0.05). Thus, findings of higher CRP values in adults with sleep-disordered breathing and correlations of these values with polysomnography indices were not confirmed in children.
Analysis of the lympho-plasmacytic infiltrate in Crohn's disease with special reference to identification of lymphocyte-subpopulations.
Authors: S G Meuwissen, T M Feltkamp-Vroom, A B De La Riviere, A E Von Dem Borne, G N Tytgat
Journal: Gut (1976)

Lympho-plasmacytic infiltrates in cryostat sections (resected small intestine or colon specimens and rectal biopsies) from 29 patients with Crohn9s disease (CD) were studied with the immunoperoxidase and immunofluorescence technique, by means of specific anti-human lymphocyte globulin (ALG) and specific anti-human T-lymphocyte globulin (ATG). Control specimens were obtained from 16 patients with ulcerative colitis (UC) and 12 subjects without inflammatory bowel disease. Characteristic transmural inflammatory infiltrates in CD consisted mainly of lymphocytes. A wide variation of the relative T-cell proportion was observed. However, in contrast with UC, abundant numbers of T-lymphocytes in CD were often detected, particularly in the deeper layers of the bowel wall. Furthermore, in serial sections immunoglobulin-containing plasma cells were counted, using specific anti-IgA, -IgM, and -IgG antisera. A significant reduction of the IgA/IgM plasma cell-ratio was found in CD in comparison with UC and controls. Our results indicate that in CD a chronic cellular immune reaction is going on within the diseases gut, involving increased numbers of lymphocytes and particularly T-cells. It remains to be established whether a deficient IgA barrier has to be considered of primary pathogenetic importance.
Second Malignant Neoplasms: Assessment and Strategies for Risk Reduction
Authors: Marie E. Wood, Victor Vogel, Andrea Ng, Lewis Foxhall, Pamela Goodwin, Lois B. Travis
Journal: Journal of Clinical Oncology (2012)

Improvements in early detection, supportive care, and treatment have resulted in an increasing number of cancer survivors, with a current 5-year relative survival rate for all cancers combined of approximately 66.1%. For some patients, these survival advances have been offset by the long-term late effects of cancer and its treatment, with second malignant neoplasms (SMNs) comprising one of the most potentially life-threatening sequelae. The number of patients with SMNs is growing, with new SMNs now representing about one in six of all cancers reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. SMNs reflect not only the late effects of therapy but also the influence of shared etiologic factors (in particular, tobacco and excessive alcohol intake), genetic susceptibility, environmental exposures, host effects, and combinations of factors, including gene-environment interactions. For selected SMNs, risk is also modified by age at exposure and attained age. SMNs can be categorized into three major groups according to the predominant etiologic factor(s): (1) treatment-related, (2) syndromic, and (3) those due to shared etiologic exposures, although the nonexclusivity of these groups should be underscored. Here we provide an overview of SMNs in survivors of adult-onset cancer, summarizing the current, albeit limited, clinical evidence with regard to screening and prevention, with a focus on the provision of guidance for health care providers. The growing number of patients with second (and higher-order) cancers mandates that we also further probe etiologic influences and genetic variants that heighten risk, and that we better define high-risk groups for targeted preventive and interventional clinical strategies.
Preserving the Lifesaving Power of Antimicrobial Agents
Authors: James M. Hughes
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Evidence-Based Nutrition Guidelines for Critically Ill Adults—Reply
Authors: Gordon S. Doig
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal