tbuckley/cabot-search huggingface dataset:
Abstract 789: Determination of MAPK and Wnt pathway activity in esophageal cancer
Authors: Nicholas B. Shannon, Christopher J. Peters, Jonathan R. Rees, James S. Hardwick, Chunsheng Zhang, Richard H. Hardwick, Rebecca C. Fitzgerald
Journal: Cancer Research (2010)

Abstract Introduction: Gastro-esophageal adenocarcinomas are rapidly increasing in incidence and have a five year survival of less than 14%. Analysis of signaling pathways in gastro-esophageal adenocarcinomas can be used as a route to identifying possible therapeutic targets. Aims and methods: We had already identified MAPK and Wnt pathways as important in this disease. The aim of this work was to identify biomarkers of pathway activation for future application to primary tumors for selection of targeted therapies. Three cell lines (CP-B, CP-C, CP-D) without constitutive activation were stimulated with exogenous ligands for the Wnt or MAPK or pathways. The TGFβ pathway was also stimulated as a negative control to test biomarker specificity. The expression of potential biomarkers of transcriptional activity was then profiled using real time PCR. To determine applicability of these markers to human tissue the expression of these markers was assessed in an expression array data set consisting of 75 gastro-esophageal adenocarcinomas. Results: Out of 8 (MAPK) and 13 (Wnt) potential markers, three markers were selected as specific for the MAPK pathway (EGR-1, JUN and FOSL1) or the Wnt pathway (BMP4, TCF7, LEF1). All markers had upregulation of expression of at least 2 fold that were specific to activation of the relevant pathway (Table 1).Table 1.Fold changes of expression upon activation by stimulation with exogenous ligandsMarkerEGF (MAPK pathway)LiCl (Wnt pathway)TGFβ (TGFβ pathway)P-value (ANOVA)EGR-1130.50.91.3&amp;lt; 10-4JUN3.31.21.0&amp;lt; 10-4FOSL111.02.60.6&amp;lt; 10-4BMP42.18.31.5&amp;lt; 10-4LEF10.523.30.5&amp;lt; 10-4TCF72.44.80.7&amp;lt; 10-4 Next we assessed the expression of selected markers in 75 gastro-esophageal adenocarcinomas for which expression profiling data was available. In these tumors 27 (36%) had activation of the MAPK pathway alone, 10 (13%) had activation of the Wnt pathway alone, and a further 12 (16%) had activation of both pathways. Conclusions: We have determined a set of markers which can be used to assess pathway activation of the MAPK and Wnt pathways in gastro-esophageal adenocarcinomas. External validation of these pathway activation markers is ongoing using multiplex PCR as a prelude to a clinical trial of targeted therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 789.
Frequent eye movements in babies linked to autism, researchers say
Authors: J. Wise
Journal: BMJ (2015)

More frequent eye movements in babies have been linked with a later diagnosis of autism spectrum disorder in research funded by the Medical Research Council.

The researchers said that this work was at an early stage and eye movement alone was not a reliable indicator that a child may later be diagnosed with autism spectrum disorder.1 But they said that the findings may contribute to better ways of identifying babies with early signs …
DNA β-Amyloid&lt;sub&gt;1-42&lt;/sub&gt; Trimer Immunization for Alzheimer Disease in a Wild-Type Mouse Model
Authors: Doris Lambracht-Washington, Bao Xi Qu, Min Fu, Todd N. Eagar, Olaf Stüve, Roger N. Rosenberg
Journal: JAMA (2009)

Context DNA ␤-amyloid 1-42 (A␤42) trimer immunization was developed to produce specific T helper 2 cell (T H 2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of A␤42 peptide that occur in the brain of patients with AD.Objective To compare the immune response in wild-type mice after immunization with DNA A␤42 trimer and A␤42 peptide. Design and InterventionWild-type mice received either 4 µg of DNA A␤42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 µg of human A␤42 peptide with the adjuvant Quil A (n=8).Titers, epitope mapping, and isotypes of the A␤42-specific antibodies were analyzed.Main Outcome Measures Antibody titers, mapping of binding sites (epitopes), isotype profiles of the A␤42-specific antibodies, and T-cell activation.Results DNA A␤42 trimer immunization resulted in antibody titers with a mean of 15 µg per milliliter of plasma.The isotype profile of the antibodies differed markedly.A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a T H 2 type of immune response (IgG1/IgG2a ratio of 10).The peptideimmunized mice showed a mixed T H 1/T H 2 immune response (IgG1/IgG2a ratio of 1) (PϽ.001).No increased T-cell proliferation was observed in the DNA-immunized mice (P=.03). ConclusionIn this preliminary study in a wild-type mouse model, DNA A␤42 trimer immunization protocol produced a T H 2 immune response and appeared to have low potential to cause an inflammatory T-cell response.
Prophylactic Oral Amiodarone for the Prevention of Arrhythmias That Begin Early After Revascularization, Valve Replacement, or Repair
Authors: L. Brent Mitchell, Derek V. Exner, D. George Wyse, Carol J. Connolly, Gregory D. Prystai, Alexander J. Bayes, William T. Kidd, Teresa Kieser, John J. Burgess, André Ferland, Charles L. MacAdams, Andrew Maitland
Journal: JAMA (2005)

Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results.To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups.Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year.Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative beta-blockers.Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day.Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative beta-blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative beta-blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality.Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251706.
Isoniazid Prophylaxis in New Immigrants
Authors: HAROLD I. PASSES
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 November 1981Isoniazid Prophylaxis in New ImmigrantsHAROLD I. PASSES, M.D.HAROLD I. PASSES, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-95-5-657_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: There is a serious omission in both "Should Young Adults With a Positive Skin Test Take Isoniazid?" (1), and the editorial "Evaluating Isoniazid Preventive Therapy: The Need For More Data" (2). This omission concerns new arrivals not yet covered by the data assessed in both articles.Recently, the U.S. immigration authorities announced that 800 000 aliens arrived in the United States in 1980, as well as an unknown number of "illegados," perhaps over 1 million. Add these to the very large number of recent immigrants already here, somewhere between 8 million and 12 million persons, and you...References1. TAYLORARONSONDELBANCO WMT. Should young adults with a positive tuberculin test take isoniazid? Ann Intern Med. 1981;95:808-13. LinkGoogle Scholar2. COMSTOCK G. Evaluating isoniazid preventive therapy: the need for more data. Ann Intern Med. 1981;95:817-9. Editorial. 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 November 1981Volume 95, Issue 5Page: 657-657KeywordsIsoniazidPreventive medicineProphylaxisSkin testsYoung adults Issue Published: 1 November 1981 PDF DownloadLoading ...
Dynamic DNA methylation programs persistent adverse effects of early-life stress
Authors: Chris Murgatroyd, Alexandre V Patchev, Yonghe Wu, Vincenzo Micale, Yvonne Bockmühl, Dieter Fischer, Florian Holsboer, Carsten T Wotjak, Osborne F X Almeida, Dietmar Spengler
Journal: Nature Neuroscience (2009)
PTU-176 Retrospective Audit of Antibiotic use in Patients admitted to Intensive Care Unit (ICU) with Severe Acute Pancreatitis
Authors: O Jalil, L Hopkins, A Rasheed
Journal: Gut (2013)

<h3>Introduction</h3> The Atlanta classification divides patients with acute pancreatitis (AP) into two groups, mild and severe. The severe form (severe acute pancreatitis, SAP ) is best managed in HDU or ICU setting and is associated with high morbidity and mortality despite best efforts at early diagnosis and timely intervention. The use of antibiotics in SAP is controversial. The aim of the audit is to compare antibiotic use and mortality of patients admitted to the ICU against national standards. <h3>Methods</h3> Retrospective audit of management and outcome of consecutive patients admitted to ICU with SAP during the period of 2007–2010. The timing of antibiotic use, the agent(s) used and the site of infection were compared. <h3>Results</h3> Of 51 patients, 42 received antibiotics. 63% ( n = 32) of patients were started antibiotics within 48 hrs of hospital admission. The first choice antibiotics were cefuroxime and metronidazole in 45% of cases, co-amoxiclav and metronidazole in 12% of cases and tazocin ± metronidazole in 14% of cases. In 26% of cases a combination of imipenem ±fluconazole ± gentamicin ± vancomycin was used. Three patients were confirmed to have pancreatic infections based on positive culture and 10 patients had extra-pancreatic infections. Four patients had bacteraemia, 4 had chest infections, 2 had UTI and one had Clostridium difficle. All extra-pancreatic infections had Gram negative bacilli as a causative organism. Antibiotic use did not improve survival, nor was there any observed survival benefit when the different antibiotic agents were compared (p = 0.7 and 0.4 respectively). The timing of antibiotic use also does not appear to confer a survival benefit (p = 0.5). All patients with proven pancreatic infection died, there was not a significant difference in survival in those with extra-pancreatic infections (p = 0.2). <h3>Conclusion</h3> Current guidelines recommend the use of antibiotics only in the presence of proven infection. Given that a majority of patients were commenced on antibiotics within 48hrs of admission and that only a minority were shown to have proven infection it would seem that adherence to this guideline has been poor. It has been suggested that early antibiotic use without proven infection may lead to increased antimicrobial resistance. This audit has demonstrated that early antibiotic use does not benefit survival in severe acute pancreatitis. The choice of agent is important as no single combination has been shown to be advantageous. The agent selected should be based upon clinical findings and laboratory evidence as to the organism(s) present and their susceptibilities. Further work could investigate whether antibiotic use might reduce morbidity in SAP. Other therapeutic strategies should be investigated in order to try to improve survival in this patient group. <h3>Disclosure of Interest</h3> None Declared
U-2932: two clones in one cell line, a tool for the study of clonal evolution
Authors: H Quentmeier, R M Amini, M Berglund, W G Dirks, S Ehrentraut, R Geffers, R A F MacLeod, S Nagel, J Romani, M Scherr, M Zaborski, H G Drexler
Journal: Leukemia (2012)
Raynaud's Disease Among Women and Girls
Authors: RAY W. GIFFORD, EDGAR A. HINES
Journal: Circulation (1957)

The diagnosis of Raynaud's disease was suspected in 756 female patients at the Mayo Clinic from 1920 through 1945. The diagnosis was substantiated from the records of the initial examination or from the follow-up data or examination in 474. The clinical characteristics, including diagnostic criteria, clinical course, complications, and sequelae are discussed.
EPA priorities for biologic markers research in environmental health.
Authors: J R Fowle, K Sexton
Journal: Environmental Health Perspectives (1992)

Recent advances in molecular and cellular biology allow for measurement of biologic events or substances that may provide markers of exposure, effect, or susceptibility in humans. The application of these new and emerging techniques to environmental health offers the possibility of significantly reducing the uncertainties that traditionally hamper risk assessments. The U.S. Environmental Protection Agency (EPA) health research program emphasizes the validation of appropriate biologic markers and their application to high-priority Agency issues. The rationale for EPA's biomarker research program is presented, and future research directions are discussed. Exposure biomarkers will receive most of the research emphasis in the near term, particularly body burden indicators of exposure to high-priority chemicals, such as benzene, ozone, selected heavy metals, and organophosphate pesticides. Research on effects biomarkers will attempt to validate the relationship between the observed biological effects and adverse health consequences in humans, especially for cancer, pulmonary toxicity, immunotoxicity, and reproductive/developmental toxicity.
Progressive linear lichen planus and metastatic carcinoma
Authors: G.F. Sciallis II, C.L. Loprinzi, M.D.P. Davis
Journal: British Journal of Dermatology (2005)

Journal Article Progressive linear lichen planus and metastatic carcinoma Get access British Journal of Dermatology, Volume 152, Issue 2, 1 February 2005, Pages 399–401, https://doi.org/10.1111/j.1365-2133.2005.06416.x Published: 01 February 2005
X-Rated Words
Authors: Hugh H. Hussey
Journal: JAMA (1976)

The careful writer (speaker) faces a dilemma when he or she wishes to write (speak) about a person of either sex but not both. Often he or she resorts to the his/her construction, or he or she writes (speaks) of "his," hoping that the reader (listener) will not think of him or her as a male chauvinist. Evidently, it's a troublesome problem when one is writing (speaking) of a person and wishes to indicate that the person's sex is not a factor. (Please do not misinterpret the word "sex";<i>sex</i>is not implied.) Professor Attlebury Smith-Petri, known to some of his associates as "the Artful Dodger," with no apologies to Dickens, has proposed the use of a coined word "hisser" to solve the dilemma. The professor's associates at Elsewhere College contend that he has simply eradicated a virgule and produced a word that simulates a snake's vocal rendition or that
Phase I Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors: A Pediatric Oncology Group Study
Authors: Victor M. Aquino, Steve D. Weitman, Naomi J. Winick, Susan Blaney, Wayne L. Furman, James L. Kepner, Peter Bonate, Mark Krailo, Wenchun Qu, Mark Bernstein
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the dose limiting toxicity (DLT), maximum-tolerated dose (MTD), and pharmacokinetic profile of tirapazamine (Sanofi Synthelabo Research, Malvern, PA) combined with cyclophosphamide in children with recurrent solid tumors. Patients and Methods Patients received a 2-hour infusion of tirapazamine, followed by 1,500 mg/m 2 cyclophosphamide, and mesna once every 3 weeks. Dose escalation of tirapazamine began at 250 mg/m 2 and was increased by 30% in subsequent cohorts. If DLT was hematologic, less-heavily pretreated patients were to be enrolled until their DLTs were encountered, and MTDs defined. Pharmacokinetic profiles were also characterized. Results Twenty-three patients were enrolled onto the study. Pharmacokinetic data were calculated for 22 patients. Prolonged neutropenia was the DLT at 420 mg/m 2 in heavily pretreated patients. Grade 3, reversible ototoxicity was the DLT in less-heavily pretreated patients at 420 mg/m 2 . Two (one with neuroblastoma and one with rhabdomyosarcoma) had partial responses. One child with neuroblastoma had prolonged stable disease (10 cycles) at a dose of 250 mg/m 2 . This patient had disease detectable in the bone marrow only and all evidence of bone marrow involvement resolved for 17 cycles of therapy. Four other patients had stable disease. An apparent dose-proportional increase in tirapazamine maximal concentration and area under the curve last was observed. Tirapazamine clearance, volume of distribution at steady-state, and terminal half-life did not appear to be dose-dependent. Conclusion The recommended dose of tirapazamine given with 1,500 mg/m 2 of cyclophosphamide once every 3 weeks is 325 mg/m 2 . Neutropenia and ototoxicity were dose-limiting. Based on early evidence of antitumor activity, additional studies appear warranted.
Effects of Pneumonectomy on Pulmonary Circulation in Adult and Young Animals
Authors: ABRAHAM M. RUDOLPH, EDWARD B. D. NEUHAUSER, RICHARD J. GOLINKO, PETER A. M. AULD
Journal: Circulation Research (1961)

Serial observations were made on the changes in pulmonary-artery pressure, radiological, and histological features of the pulmonary vasculature after pneiunonectomy or ligation of a single pulmonary artery in adult dogs and in puppies. Acute occlusion produced only insignificant changes in the pulmonary-arterial pressure. After one to two days, a rapid rise in pulmonary-arterial pres sure was observed. The pressure then gradually rose and in the subsequent months reached somewhat higher levels in the puppies as compared with the adult dogs. A decrease in pulmonary-arterial pressure which occurred after the initial rise in pressure was noted in one adult dog and two puppies. Comparison of the histology of the remaining lung with the control lung showed the development of medial hypertrophy of the smaller and medium-sized vessels, with an increase in the wall to lumen ratio. No significant difference was noted between the histological features of the adult and young animals. Pulmonary arteriograrns revealed progressive dilatation and tortuosity of the main pulmonary artery and its major branches, less striking in the puppies as compared with the adult dogs.
Nurse–Community Health Worker Team Improves Diabetes Care in American Samoa
Authors: Judith D. DePue, Shira Dunsiger, Andrew D. Seiden, Jeffrey Blume, Rochelle K. Rosen, Michael G. Goldstein, Ofeira Nu'usolia, John Tuitele, Stephen T. McGarvey
Journal: Diabetes Care (2013)

To evaluate the effectiveness of a culturally adapted, primary care-based nurse-community health worker (CHW) team intervention to support diabetes self-management on diabetes control and other biologic measures. Two hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were randomly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care. Participants had a mean age of 55 years, 62% were female, mean years of education were 12.5 years, 41% were employed, and mean HbA1c was 9.8% at baseline. At 12 months, mean HbA1c was significantly lower among CHW participants, compared with usual care, after adjusting for confounders (b = -0.53; SE = 0.21; P = 0.03). The odds of making a clinically significant improvement in HbA1c of at least 0.5% in the CHW group was twice the odds in the usual care group after controlling for confounders (P = 0.05). There were no significant differences in blood pressure, weight, or waist circumference at 12 months between groups. A culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U.S. Territory of American Samoa. This represents an important translation of an evidence-based model to a high-risk population and a resource-poor setting.
Smoking and Cervical Cancer: Cause or Coincidence-Reply
Authors: Peter M. Layde
Journal: JAMA (1989)

<h3>In Reply.—</h3> Although cigarette smoking may well make a causal contribution to cervical carcinogenesis, Dr Winkelstein overstates the case with his implication that the association of sexual activity with cervical cancer is as likely to be due to confounding as the association of smoking with cervical cancer. The preponderance of evidence from many studies indicates that the major etiologic factor for cervical carcinogenesis is a sexually transmitted agent.<sup>1</sup>For example, cervical cancer in virgins is very rare,<sup>1,2</sup>while it is not at all uncommon in nonsmokers who have multiple sexual partners. In addition, for the reasons stated in my editorial, I believe sexual activity is a particularly poor surrogate of the likelihood of infection with the sexually transmitted agent of cervical cancer. This both lowers the apparent relative risk (or odds ratio) for the association of sexual activity and cervical cancer and also severely impairs the ability to
A piece of my mind. White blood
Authors: D. C. Weaver
Journal: JAMA (1989)

I moved the slide slowly across the microscope stage (sticky in the tropical heat), paused near the edge of the smear of blood, and focused. Even with the instrument at the lowest magnification, I saw that this boy's blood had far, far too many white cells. So many, in fact, that the blood had become almost a ghostly white. I changed the objective to a higher power and peered into the nucleus, the very center of the cell. If cells have souls they must lie there, locked within the regulators of the genes. These nuclei were, in the pathologist's parlance, primitive, and the regulators that control them were running wild. If my suspicions were correct, the marrow of the bones was already filled with these primeval white cells and they were spilling out into the blood—leukemia. This past February I went to Grenada, the isle of spice, as it is known, on a working vacation to practice tropical medicine. I found the island to be a place of extinct volcanoes, rain forests, blue seas, spices, gentle people, and poverty. The hospital, a converted 19th-century army barracks, sat on a hill overlooking a blue harbor. The interior, at first glance,