tbuckley/cabot-search huggingface dataset:
Recent advances: Management of self poisoning
Authors: A. L Jones, G. Volans
Journal: BMJ (1999)

Around 15%-20% of the workload of medical units and 10% of the workload of accident and emergency departments in the United Kingdom are due to self poisoning. 1 2 Episodes of self poisoning in the United Kingdom continue to rise, particularly in young men, and alcohol is often taken with the overdose.2 In general the severity of poisoning has diminished over the past 10 years with the introduction of safer drugs, such as newer serotonin reuptake inhibitors, but the total number of deaths from poisoning in the United Kingdom remains steady at 4000 per year, and the commonest cause of death by poisoning is carbon monoxide. 2 3 This article highlights several specific advances in the management of poisoning over the past two or three years.

We searched Medline and Embase with the keywords “poisoning,” “intoxication,” “toxin,” and “overdose.” We included topics as a result of discussion with colleagues in clinical toxicology in the United Kingdom, Europe, Australia, and the United States.

The American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists have recently produced new guidelines on gut decontamination on the basis of consensus and evidence based statements.4–6 It is important to understand the advances in understanding and changes in practice that come from the guidelines, but the evidence base for them is limited.4–7

### Activated charcoal

Activated charcoal should be given as a single dose (50 g for an adult, 1 g/kg body weight for a child up to 12 years) up to 1 hour after ingestion of a substantial amount of toxin.4 Beyond this time adsorption is reduced. 4 8 What constitutes a substantial amount of toxin depends on the toxin but in general it is a dose expected to cause moderate to severe toxicity. The …
Abstract 5571: Genome-wide crosstalk of estrogen and progesterone signaling in breast cancer
Authors: Hari Singhal, Geoffrey Greene
Journal: Cancer Research (2014)

Abstract Estrogen receptor alpha (ER) and progesterone receptor (PR) are established biomarkers in breast cancer and receptor-targeted therapies are routinely used in breast cancer treatment. Estrogen receptor exists as two subtypes, ERα and ERβ, and PR has two isoforms PRA and PRB. Furthermore, millions of women worldwide use estrogen and progesterone formulations as oral contraceptives and hormone replacement therapies. Although critical crosstalk occurs between estrogen and progesterone signaling, the global nature and mechanistic details of this interaction are not known. Our central hypothesis is that there is genome-wide dominance of progesterone over estrogen signaling in breast cancer. This hypothesis is based on our novel findings that gene expression and proliferation of T47D and ZR75 breast cancer cells upon co-treatment with estrogen and progesterone is similar to progesterone-only treatment and is significantly different from estrogen-only treatment. Furthermore, four derivative T47D sublines that lack either of the PR isoforms, both the isoforms of PR or ER along with PR are being used to study ERα-, PRA- and PRB-specific regulatory networks. ER- and PR-regulated gene networks are defined by correlating ER and PR genome binding data obtained from ChIP-seq with gene expression data of T47D cells acquired using RNA-seq. For instance, genes that are known to be important in breast carcinogenesis, such as GATA3, GREB1, PDZK1, FOXA1 are found to be co-regulated by ER and PR. Subsequently the intersection of identified ER- and PR-regulated gene networks will be studied and their clinical value will be assessed. Transcription cofactors FOXA1 and NF1C are critical for transactivation by ER and PR. Knockdown of these cofactors in T47D cells alters the ER/PR crosstalk in these cells. To validate the clinical value of genes co-regulated by ER and PR in breast cancer, meta-analysis for their enrichment in established breast cancer signatures will be done. Cluster analysis of the expression of these genes in patient tumor samples that differ in clinical outcomes will also be performed. Finally, a Kaplan-Meier survival analysis will be done to study a correlation between expression of these genes and patient survival. These innovative studies will determine the global influence of progesterone over estrogen signaling in breast cancer. The resulting map of ER- and PR-regulated gene networks will lead to the optimization of breast cancer treatments, hormonal contraceptives and hormone replacement therapies. Citation Format: Hari Singhal, Geoffrey Greene. Genome-wide crosstalk of estrogen and progesterone signaling in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5571. doi:10.1158/1538-7445.AM2014-5571
Abstract 4632: Left Atrial Size and Advancing Age Predict the Need to Restart Drug Therapy after AF Ablation to Maintain AF Control
Authors: John Harding, Erica Zado, Mathew Hutchinson, Michael Riley, Rupa Bala, Fermin Garcia, David Lin, Joshua Cooper, Sanjay Dixit, Ralph Verdino, Edward Gerstenfeld, Andrea Russo, David Callans, Francis Marchlinski
Journal: Circulation (2008)

Background : While many patients (pts) remain free of atrial fibrillation (AF) without anti-arrhythmic drug(AAD) therapy after ablation, some pts require re-initiation of medications to control AF long-term. Factors associated with need for reinstituting AAD have not been identified. Methods: A total of 578 pts who underwent AF ablation and demonstrated AF control for at least 12months were included in this study. The ablation included proximal pulmonary vein (PV) isolation with entry and exit block and elimination of non PV triggers. AAD were reinitiated if with ECG documented AF recurrence after the 2 month blanking period. Confirmation of AF control was based on symptoms and transtelephonic ECG monitoring at 6 mos, 12 mos, and with symptoms. Clinical variables were compared between each group by univariate analysis to determine if significant differences existed. Significant parameters were included in a multivariate analysis to determine interaction between variables. Results: Table 1 delineates clinical parameters included in the analysis, with unadjusted P values for each variable. Multivariate analysis with forward and backward regression identified larger LA size and advancing age as only factors which correlated with the need for AAD therapy after ablation to maintain AF control. Conclusions: Increased LA size and advancing age are clinical parameters which suggest progressive fibrosis of the LA. In our analysis, these two variables strongly predicted the need to restart AAD therapy after proximal PV ablation and elimination of non PV triggers in order to maintain long-term control of AF. Table 1
Antidepressant Warning Focuses Attention on Unmet Need for Child Psychiatrists
Authors: Sarah Ringold
Journal: JAMA (2005)

The controversial black-box warning for antidepressants describing the possible link between use of these drugs and suicide in adolescents has sparked an active debate regarding the appropriate treatment of depression in younger patients. The warning, required in the labeling of at least 32 commonly prescribed antidepressants, not only focuses attention on concerns about these medications for pediatric patients but also highlights a widening gap between the needs of the approximately 2.7 million US children and adolescents with significant depression and the nation's relatively small number of trained child psychiatrists. However, a growing recognition of this unmet need is driving new efforts to address the problem. Primary care pediatricians, family medicine practitioners, and psychiatrists are collaborating to formulate and promote guidelines and other measures.
When can odds ratios mislead?
Authors: J. Deeks, M. B Bracken, J. C Sinclair, H. T. O. Davies, M. Tavakoli, I. K. Crombie
Journal: BMJ (1998)

Guidelines for cervical screening await scientific evaluationEditor-In a news item about cervical screening in England 1 Wise refers to a report by the National Audit Office. 2 The office is particularly critical of serious failings in the interpretation of cervical smears in a small number of laboratories.The laboratory at the Hospital of St Cross in Rugby is included among these laboratories.In fact, a massive rescreening exercise at the hospital did not find any serious errors of interpretation, and the original reports were considered to be substantially correct and within the accepted operating limits of the smear test.The National Audit Office and the public assume that any deviation from the national guidelines for reporting rates represents mistakes by the laboratory.It is therefore interesting that, although the results at the hospital in Rugby were outside these guidelines, no serious errors were identified.This raises the question of whether the guidelines are an appropriate measure of laboratory performance.The guidelines themselves have come under considerable criticism in the pathology literature because of the lack of scientific evidence on which they are based. 3 One of their own authors has been particularly outspoken on the subject. 4 Though some of these arguments may seem of academic interest, cytology departments are being forced to close or merge as a result of the guidelines, which await scientific evaluation.Many staff feel threatened by the prescriptive way in which the guidelines have been introduced and applied and by the lack of understanding by the lay public and media of the limitations of the smear test.The incidence of and mortality from cervical cancer in the United Kingdom have shown accelerated falls since the introduction of organised screening (J Patnick, NHS cervical screening programme information sheet, 21 Nov 1996).Of course there is room for improvement, but it is ironic that the publication of various reports designed to improve the service could lead to its eventual collapse through staff leaving the profession.
MYXEDEMA—CONTROLLED BY THYROID EXTRACT FOR FIFTY-TWO YEARS: REPORT OF A CASE
Authors: A M BURGESS
Journal: Annals of Internal Medicine (1946)

Case Reports1 July 1946MYXEDEMA—CONTROLLED BY THYROID EXTRACT FOR FIFTY-TWO YEARS: REPORT OF A CASEALEX. M. BURGESS, M.D., F.A.C.P.ALEX. M. BURGESS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-25-1-146 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhen the diagnosis of myxedema has been made and thyroid therapy has produced the usual spectacular return of the patient to normal life, the question as to ultimate prognosis is asked. The usual answer is a statement that as long as the patient continues to receive thyroid in adequate dosage she will continue to live out the rest of her life unhampered by the deficiency in the activity of her own thyroid gland and that she may plan and carry on her life as may any normal person. That this is true is borne out by the facts here reported...Bibliography1. MEANS JH: The thyroid and its diseases, 1937, J. B. Lippincott Company, Philadelphia. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Providence, R. I.*Received for publication May 29, 1945. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Thyroid GlandDie SchilddrüseComparative clinical pharmacology of thyroid hormonesThe Thyroid GlandKrankheiten der Schilddrüse 1 July 1946Volume 25, Issue 1Page: 146-150KeywordsThyroid ePublished: 1 December 2008 Issue Published: 1 July 1946 PDF downloadLoading ...
Distinct Patterns of Autoantibodies Against G-Protein–Coupled Receptors in Chagas' Cardiomyopathy and Megacolon
Authors: Gerd Wallukat, Silvia Gilka Muñoz Saravia, Annekathrin Haberland, Sabine Bartel, Raul Araujo, Gregorio Valda, Diana Duchen, Ivan Diaz Ramirez, Adrian Constantin Borges, Ingolf Schimke
Journal: Journal of the American College of Cardiology (2010)
Oral mucosa as a source of Mycobacterium leprae infection and transmission, and implications of bacterial DNA detection and the immunological status
Authors: T.S. Martinez, M.M.N.R Figueira, A.V. Costa, M.A. Gonçalves, L.R. Goulart, I.M.B. Goulart
Journal: Clinical Microbiology and Infection (2010)
Abstract 11969: Association of Amiodarone Use With Acute Pancreatitis in Patients With Atrial Fibrillation: A Nested Case-Control Study
Authors: Alvaro Alonso, Richard F MacLehose, Pamela L Lutsey, Suma Konety, Lin Y Chen
Journal: Circulation (2014)

Background: Amiodarone is an antiarrhythmic frequently used by atrial fibrillation (AF) patients. Case reports suggest that amiodarone use may cause acute pancreatitis. This potential adverse effect of amiodarone has not been explored in large studies. Methods: We conducted a case-control study nested in the MarketScan® Research Database, which includes healthcare claims from >4 million individuals in the US. Cases were patients with non-valvular AF (NVAF) admitted to the hospital with a primary diagnosis of acute pancreatitis during the period 2007-12. We selected 5 controls with NVAF per case matched by sex, year of birth, and enrollment date in MarketScan. Information on use of amiodarone, other medications, and comorbidities were obtained from pharmacy, inpatient, and outpatient claims. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) of acute pancreatitis by use of amiodarone and other antiarrhythmics, as well as time since initi...
Surgeon awarded libel damages of £175 000
Authors: Clare Dyer
Journal: BMJ (2001)

A consultant thoracic surgeon attacked in a television news report by Channel 4 News and in an ITN television programme, Great Frauds , accepted libel damages of £175 000 ($245 000) in an out of court settlement last week.

Channel 4 Television Corporation and the investigative journalist Duncan Campbell agreed to pay Joe Rahamim, a surgeon at Derriford Hospital in Plymouth, damages of £100 000, and ITN agreed to pay £75 000. The defendants will also pay legal costs estimated at £750 000, including a £250 000 “success fee” on top of their £250 000 costs to Mr Rahamim's solicitors, Peter Carter-Ruck and Partners, who acted on a “no win, no fee” basis.

In a statement to the …
Abstract 13327: Assessing Right Ventricular-Pulmonary Circulation Reserve During Exercise Challenge in Patients with Heart Failure and Severely Depressed Right Heart Function at Rest
Authors: Greta Generati, Francesco Bandera, Marta Pellegrino, Valentina Labate, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2014)

Background:  Right ventricular (RV) dysfunction at rest has a significant prognostic role in heart failure (HF) syndrome and its combination with pulmonary artery systolic pressure (PASP) is useful for risk stratification. Different response to exercise of echo-derived tricuspid annular systolic excursion (TAPSE), as RV function indicator, and PASP may provide further clinical stratification in a population of HF patients with advanced bi-ventricular disease and depressed RV function. Aim: We aimed to assessed RV-pulmonary circulation functional response to maximal exercise in a population of HF patients with severe RV systolic impairment (TAPSE   Methods:  39 HFrEF patients (mean age 64 y, male 82%, ischemic etiology 64%, LVEF 33±10%, NYHA class I, II, III, IV 20, 21, 42,17 %, mean TAPSE 13±2 mm, PASP 43±19 mmHg) underwent a maximal symptoms-limited CPET on a tiltable cycle ergometer using an incremental personalized ramp protocol and stress echo.   Results:  Study population as divided in two groups according to the presence RV functional reserve increase of TAPSE at peak exercise >20%). Despite similar left ventricular (LV) function and RV systolic impairment at rest, patients with impaired RV reserve (Group B) showed lower exercise capacity (peak VO 2 , peak O 2  pulse), associated with more advanced cardiac remodeling and more severe degree of mitral regurgitation (MR) both at rest and during exercise.   Conclusions:  In HF patients an impaired RV function at rest may not invariably lead to an unfavorable RV adaptive response to exercise. Testing the degree of RV functional reserve and RV-pulmonary circulation coupling during exercise can be useful even in the most advanced stages of disease to unmask different clinical phenotypes and, very likely, different levels of risk.
Abstract 17356: Accumulation of Risk Factors Increases the Risk of Fatal Arrhythmic Events in Patients with Ischemic Heart Disease or Those with Dilated Cardiomyopathy -A Report from the CHART-2 Study-
Authors: Hiroyuki Satake, Koji Fukuda, Yasuhiko Sakata, Makoto Nakano, Masateru Kondo, Yuhi Hasebe, Masato Segawa, Hiroaki Shimokawa
Journal: Circulation (2014)

Background:  Although the secondary prevention of fatal arrhythmic events (FAEs) with implantable cardioverter defibrillator (ICD) is established, the primary prevention of FAEs with ICD for patients with structural heart disease has been controversial. Currently, ICD implantation has been recommended for patients with severe left ventricular (LV) dysfunction. In this study, we re-evaluated the current risk stratification in patients with heart failure (HF).   Methods and Results:  Among 10,219 patients with stage B/C/D HF patients registered in our CHART-2 Study, we enrolled 5,610 patients with either IHD or DCM in NYHA Class I to III who had never experienced FAEs. We prospectively examined the association between their risk factors and FAEs (sudden cardiac death, arrhythmic death, sustained ventricular tachycardia, ventricular fibrillation or appropriate ICD therapy). During the median follow-up of 3.2 years, 97 FAEs occurred. FAEs more frequently occurred in patients who met the Class I indication for primary prevention with ICD by the ACC/AHA Guidelines (NYHA II/III and LV ejection fraction (LVEF)≤35%) compared with those who did not (10.2 vs. 1.2%, P 200pg/ml, LV end-diastolic dimension (LVDD)>55mm, non-sustained ventricular tachycardia (NSVT) and eGFR 2 . When including the number of risk factors as a co-variable, a trend analysis showed a stepwise increase in the risk of FAEs as an increased number of risk markers; 0.3, 0.8, 1.4, 3.4, 9.4, and 16.0% from 0 to 4 and more than 5, respectively. When limited to the patients with NYHA II/III and LVEF≤35% (n=315), chronic atrial fibrillation (AF) was an independent risk factor of FAEs but not LVDD>55 mm, NSVT, BNP>200 pg/ml or eGFR 2 . In addition, FAEs rate was increased up to 33% when patients with chronic AF simultaneously had 3 or more of the following factors; BNP>200 pg/ml, LVDD>55 mm, NSVT and eGFR   Conclusions:  These results indicate that accumulation of risk factors increases the risk of FAEs in patients with either IHD or DCM, especially when chronic AF is present.
Naturally occurring human IgA autoantibodies against IgE‐DES myeloma protein
Authors: C. G. M. Magnusson
Journal: Allergy (1994)

The prevalence and specificity of naturally occurring human IgA anti-IgE autoantibodies (a-E Ab) were studied by ELISA with anti-IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid-phase protein, i.e., IgE-DES(kappa). Such detected IgA a-E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P = 0.006; n = 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P = 0.02; n = 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n = 42; GM = 48.8 AU/ml). No such difference was observed between age-matched nonatopic (n = 22; GM = 36.7 AU/ml) and atopic (n = 22; GM = 38.6 AU/ml) children. Children had significantly (P < 0.001) lower IgA a-E Ab concentrations than adults, probably as a result of age, because IgA a-E Ab concentrations and age of children were significantly correlated (n = 44; P < 0.05; r = 0.30). IgA a-E Ab concentrations were very low in cord serum (n = 32; median < 0.1 AU/ml). Sex did not influence IgA a-E Ab concentrations in any study group. The specificity of IgA a-E Ab in nine sera was studied by ELISA inhibition assay using IgE-DES myeloma as solid-phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE-DES. The inhibitions indicated that all IgA a-E Ab tested reacted in a low-affinity reaction with determinants restricted to IgE-DES, i.e., the solid-phase protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Presence or absence of plasmid in Rickettsia felis depending on the source of fleas
Authors: J.M. Rolain, I. Bitam, S. Buffet, J.L. Marié, O Bourry, C. Portelli-Clerc, J.C. Beaucournu, P. Parola, P.E. Fournier, B. Davoust, D. Raoult
Journal: Clinical Microbiology and Infection (2009)
Delineation of inhibitor-sensitive/resistant transforming mutations by mutagenesis of EGFR
Authors: Yuki Yuza, Karen A. Glatt, Jingrui Jiang, Heidi Greulich, Whei Feng, Tzu-Hsiu Chen, Yuko Minami, Haruhiko Yanagisawa, Matthew Meyerson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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EGFR and HER2 in tumor cells are well-validated target molecules in cancer treatment. Inhibition of EGFR by gefitinib (Iressa) is demonstrated to bring clinical benefit in cancer chemotherapy. However, recent progress suggests that the T790M acquired mutation occurred in EGFR kinase domain of human lung cancer render resistance against gefitinib and erlotinib (Tarceva), another EGFR-directed agent. In previous study, MP-412, a new dual EGFR/HER2 tyrosine kinase inhibitor of an anilinoquinazoline class of compound showed a potent antitumor activity against various EGFR/HER2 expressing and gefitinib-resistant human tumors in xenograft models (Abstracts #3394 and 3405, AACR 2005). To assess antitumor activity of MP-412 against human tumors with this acquired mutation in EGFR, we examined its effects on 2 established NSCLC cell lines, gefitinib-sensitive H1650 containing deletion E746-A750 mutation and H1975 containing L858R and T790M double mutations, refractory to gefitinib, implanted in nude mice. When administrated orally, MP-412 (75 and 150 mg/kg) significantly suppressed tumor growth of H1975, whereas gefitinib (113 and 225 mg/kg) and erlotinib (100 mg/kg) showed no clear effects against this cell line. In the case of H1650, all 3 agents clearly inhibited the growth of tumor at same doses. When compared the inhibitory activity of these agents against in vitro autophosphorylation of EGFR and phosphorylation of its downstream signaling molecules, AKT and MAPK of both NSCLC cells stimulated with EGF, MP-412 suppressed both EGFR autophosphorylation and phosphorylation of AKT and MAPK in 2 cell lines at the concentration of 0.1 micro mol/L or higher. In contrast, inhibitory effects of gefitinib and erlotinib against AKT and MAPK phosphorylation in H1975 cells were weak at up to 10 micro mol/L. These suggest that MP-412 may have an interesting characteristic in antitumor activity against human lung cancer containing an acquired gefitinib-resistant EGFR mutation. It is expected that MP-412 would be a therapeutic agent of cancer patients, including those refractory to gefitinib and erlotinib.