tbuckley/cabot-search huggingface dataset:
Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide
Authors: Virginia Rauh, Srikesh Arunajadai, Megan Horton, Frederica Perera, Lori Hoepner, Dana B. Barr, Robin Whyatt
Journal: Environmental Health Perspectives (2011)

In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children's Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age.The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age.In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches.On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covariates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aromatic hydrocarbons).We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. These findings are important in light of continued widespread use of CPF in agricultural settings and possible longer-term educational implications of early cognitive deficits.
The Problem-Oriented Record: A Critique from a Believer
Authors: Stephen E. Goldfinger
Journal: New England Journal of Medicine (1973)

Abstract The problem-oriented medical record has been extensively described and widely recommended by many. Its true value in patient care, teaching, and clinical research must now be proved. Potential shortcomings of the system include overemphasis on style and compartmentalization, uncritical acceptance of a data base, inefficiencies in the process of data retrieval, lack of criteria for problem formulation, and an expectation that problem orientation alone will permit effective record auditing.
Cerebral vasculitis associated with cocaine abuse
Authors: B. R. Kaye
Journal: JAMA (1987)

A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. We now include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis. (<i>JAMA</i>1987;258:2104-2106)
Frequency ofPIK3CAMutations in Chinese HER2+ Metastatic Breast Cancer Patients and Association with Clinical Benefit to Lapatinib and Capecitabine Treatment.
Authors: B. Xu, J. Zefei, D. Chua, Z. Shao, R. Luo, X. Wang, P. Yuan, B. Newstat, Y. Liu, R. Gagnon, H. Chi, A. Martin, S. Stein, L. Wang
Journal: Cancer Research (2009)

Abstract Background: Activating mutations in PIK3CA are frequent in breast cancer (Campbell et al. Cancer Res 2004;64:7678-7681). Previous analyses suggest that the presence of PIK3CA activating mutations were associated with poor clinical outcome (Li et al. Breast Can Res Treat 2006;96:91-95) and could confer resistance to treatment with trastuzumab (T) (Berns et al. Cancer Cell 2007;12:395-402). Lapatinib (L) is an oral tyrosine kinase inhibitor targeting EGFR and HER2 pathways. L plus capecitabine (C) has demonstrated efficacy in women with HER2+ metastatic breast cancer (MBC) previously treated with T (Geyer et al. N Engl J Med 2006;355(26):2733-2743). EGF109491 evaluated the efficacy of L+C in 52 Chinese HER2+ MBC patients. The clinical benefit rate (CBR) was 57.7% (PR 44% and SD 44%) and median progression free survival (PFS) was 6.3 months. The purpose of this analysis was to establish the frequency of PIK3CA mutations in this small cohort of Chinese patients and to determine if the presence of a PIK3CA mutation has any impact on clinical benefit to L+C.Methods: 38/52 patients provided tumor samples for biomarker analysis. Briefly, DNA was extracted from these tumor samples, amplified by PCR and sequenced by Pyrosequencing methods to identify the presence of frequent activating mutations in exons 9 and 20 in PIK3CA. Mutation status was tested for association with CBR and PFS using contingency table analysis and proportional hazards analysis respectively.Results:11/38 (29%) patients harbored a mutation in the PIK3CA gene, consistent with published frequencies. 9/11 mutations reside in the catalytic domain and 2/11 mutations reside in the accessory domain of the gene. There was no statistical association with CBR (p=0.639) or PFS (HR=1.01, p=0.989) in PIK3CA wildtype patients vs. PIK3CA mutant patients. PIK3CA wildtype n=27 (%)PIK3CA Mutation n=11 (%)CR0 (0)0 (0)PR12 (44%)4 (36%)SD13 (48%)5 (45%)PD1 (4%)1 (9%)Unknown1 (4%)1 (9%)HR1.01 (p=0.989) Conclusion: The frequency of PIK3CA mutations in this small cohort of Chinese HER2+ MBC patients is consistent with published frequencies. There was no statistically significant association between the presence of a PIK3CA mutation and clinical benefit to L+C in these patients. These results are in agreement with previous reports that mutations in PIK3CA do not seem to impact clinical outcome following L-containing treatment regimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1140.
1121-48 Preprocedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting
Authors: Amit Segev, Saleem Kassam, Christopher E Buller, Herbert K Lau, John D Sparkes, Philip W Connelly, Peter H Seidelin, Madhu K Natarajan, Eric A Cohen, Bradley H Strauss
Journal: Journal of the American College of Cardiology (2004)
Strangulated Epigastric Hernia
Authors: A. C. Brewer, R. Marcus
Journal: BMJ (1948)

Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas.
Working harder for longer
Authors: T. Greenhalgh
Journal: BMJ (2011)

Turning 50 brings invitations for a host of delights: cruise holidays, cheap car insurance, screening mammograms—and pre-retirement seminars at the BMA.

It didn’t seem right to turn up to a retirement planning event on a mountain bike, so I went home from work to collect the car. On arrival at BMA House I was met by a picket line. Was my projected pension so high, I wondered, that people were protesting against it? No such luck. The placards were directed at the minister of …
Statistics Are Still Fragile
Authors: Lee N. Hames
Journal: JAMA (1974)

A July 24, 1972, JAMA editorial entitled Be Careful With Statistics—They're Fragile urged physicians to be especially alert to myths and half-truths that have greatly delayed life-saving efforts. It pointed out that we cannot logically attack the problems in medicine or anywhere else if we handle or interpret statistics carelessly.  A situation has arisen recently that we believe calls for reemphasizing the ideas expressed in that editorial. Because of the energy shortage, a nationwide 55-mph speed limit was introduced early this year. Almost immediately, the number of fatalities on our highways dropped dramatically. In January of this year, for instance, there were 853 fewer deaths as compared to January 1973. Pennsylvania's reduction was 50% during the same period, while New Jersey dropped 49%, and New York 38%. Overall, in the first three months of this year, the total number of lives lost on our highways dropped almost 25% from what
Civil servants suppress evidence on homeopathy on NHS website after lobbying from prince's charity
Authors: I. Torjesen
Journal: BMJ (2013)

The way in which lobby groups and powerful people can influence government has come to light after an article on homeopathy on the public information website NHS Choices was stripped of all evidence questioning its effectiveness as a result of intervention by a charity set up by the Prince of Wales.

The Department of Health commissions the NHS Choices website from the private information company Capita to provide “objective and trustworthy information” to help patients make decisions about their health and treatment. 

But evidence obtained under the Freedom of Information Act by David Colquhoun, emeritus professor of pharmacology at University College London and a fellow of the Royal Society, indicates that the health department can edit the content if it contradicts its own policies, even if that content is based on evidence.

Emails obtained from NHS Choices by Colquhoun show that …
Abstract 2003: Role of de novo DNMTs in carcinogen induced transformation of human bronchial epithelial cells
Authors: Ivo Teneng, Carmen S. Tellez, Steven A. Belinsky
Journal: Cancer Research (2011)

Abstract Malignant tumors and cell lines are characterized by increased expression of DNMT3a and 3b. While evidence suggests that DNMT1, 3a and 3b co-operate in methylation and gene silencing during carcinogenesis, very little is known about targets for DNMT3a and 3b or their impact on the development of adenocarcinoma. We developed an in vitro model using human telomerase /cyclin dependent kinase 4 -immortalized human bronchial epithelial cell lines (HBECs) to identify key molecular changes that drive transformation and clonal outgrowth of preneoplastic lung epithelial cells during exposure to tobacco carcinogens. Carcinogen exposure (0.5µM MNU and 0.05µM BPDE) for 12 weeks induced transformation of HBEC1 and HBEC2 cells and transformation efficiency was associated with DNA repair capacity. A significant increase in DNMT1 protein was observed during carcinogen exposure while moderate increases in DNMT3a and 3b were observed in transformed cells. Increased DNMT3a and 3b levels have been reported in several cancers. We observed 5-20 fold increased expression of DNMT3a and 3b in tumor derived lung cancer cell lines. Therefore we tested the hypothesis that over expressing DNMT3a and 3b would accelerate transformation by targeting specific genes for methylation and promote full malignancy in carcinogen-treated HBECs. HBEC1 and HBEC2 clones that expressed DNMT3a or 3b at levels comparable to those observed in tumor derived cell lines were isolated, expanded and characterized. Over expression of DNMT3a or 3b had no effect on DNA repair capacity, did not affect DNMT1 expression and was not sufficient to drive transformation as evidenced by inability to form colonies on soft agar. Two clones from each cell line over expressing DNMT3a or 3b were treated with carcinogen for one hour, once a week for 12 weeks and analyzed for transformation on soft agar. Studies completed for HBEC1 indicate that expression of DNMT3b increases transformation efficiency. Soft agar analyses for HBEC2 clones are on going. Further studies will characterize the mechanism for increased transformation by examining reprogramming of the epigenome and tumorigenicity of transformed cells in xenografts This study was supported by R01 ES008801. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2003. doi:10.1158/1538-7445.AM2011-2003
Regional Differences in Current Density and Rate-Dependent Properties of the Transient Outward Current in Subepicardial and Subendocardial Myocytes of Human Left Ventricle
Authors: Michael Näbauer, Dirk J. Beuckelmann, Peter Überfuhr, Gerhard Steinbeck
Journal: Circulation (1996)

Background Recordings of outward currents in human ventricular myocytes revealed the presence of a large calcium-insensitive transient outward current. This current has been suggested to contribute significantly to regional electrophysiological heterogeneity in myocardial cells and tissue of several animal species and to cause electrical gradients across the ventricular wall. Methods and Results The patch-clamp technique was used to record action potentials and outward currents in myocytes enzymatically isolated from thin subepicardial and subendocardial layers of human nonfailing and failing left ventricle. In all subepicardial cells studied, a calcium-insensitive transient outward current (I to1 ) could be recorded with large density (10.6±1.08 pA/pF at 40 mV), whereas current density of I to1 in subendocardial cells was fourfold smaller (2.63±0.31 pA/pF, P &lt;.0001, nonfailing myocardium). In failing hearts, the density of I to1 was significantly smaller in subepicardial cells (7.81±0.53 pA/pF, P =.012) but not different in subendocardial myocytes (2.01±0.23 pA/pF, P =.25). Rate-dependent reduction of peak I to1 at a 2-Hz depolarization rate was minimal in subepicardial cells (to 92.3±1.9%), whereas peak I to1 in subendocardial myocytes was almost suppressed at 2 Hz (reduction to 13.2±2.1%, P &lt;.0001). The different rate-dependent reduction of the transient outward current was due to a much slower time course of recovery from inactivation in subendocardial cells. Kinetic data, including action potentials recorded at 35°C, allow assessment of the role of the transient outward current for electrical activity and transmural voltage gradients in human left ventricle. Conclusions Marked regional differences in density and rate-dependent properties of the transient outward current exist in subendocardial and subepicardial layers in human left ventricular myocardium, causing transmural electrical gradients that are important for normal and pathological electrical behavior of the human heart. The difference in recovery rates of the transient outward current is a distinguishing feature between subepicardial and subendocardial myocytes.
Misoprostol and Nonsteroidal Anti-Inflammatory Drugs
Authors: Fred E. Silverstein
Journal: Annals of Internal Medicine (1996)

Letters1 June 1996Misoprostol and Nonsteroidal Anti-Inflammatory DrugsFred E. Silverstein, MDFred E. Silverstein, MDUniversity of Washington Medical School; Seattle, WA 98195Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-11-199606010-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We would like to address some points raised in the editorial by Dr. Levine [1] that accompanied our recent article [2].As Dr. Levine notes, our trial was the first to provide strong evidence that misoprostol is effective in reducing the risk for serious NSAID-related complications (bleeding, obstruction, and perforation). Reductions in NSAID complications have not been shown by any other medication.Dr. Levine refers to “infrequent” serious gastrointestinal outcomes related to NSAID use. Although we agree that the absolute risk for these complications is low, widespread NSAID use—14 million regular users in the United States [3]—indicates ...References1. Levine JS. Misoprostol and nonsteroidal anti-inflammatory drugs: a tale of effects, outcomes, and costs [Editorial]. Ann Intern Med. 1995; 123:309-10. Google Scholar2. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1995; 123:241-9. Google Scholar3. Roth SH, Bennett RE. Nonsteroidal anti-inflammatory drug gastropathy: recognition and response. Arch Intern Med. 1987; 147:2093-100. Google Scholar4. Gabriel SE, Jaakkimainen RL, Bombardier C. The cost-effectiveness of misoprostol for nonsteroidal antiinflammatory drug-associated adverse gastrointestinal events. Arthritis Rheum. 1993; 36:447-59. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Washington Medical School; Seattle, WA 98195 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people 1 June 1996Volume 124, Issue 11Page: 1015KeywordsDrugsHealth careHemorrhageMedical risk factorsMorbidityMortalityNSAIDsPeptic ulcersPharmacoeconomicsUlcers Issue Published: 1 June 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Hypothalamic-pituitary-adrenal function after subarachnoid haemorrhage
Authors: J. S. Jenkins, M. Buckell, A. B. Carter, S. Westlake
Journal: BMJ (1969)

In 18 patients with a ruptured aneurysm of the anterior communicating artery on the circle of Willis hypothalamuc–pituitary–adrenal function has been assessed by the diurnal variation in plasma cortisol levels and by the response to metyrapone, dexamethasone, and pyrogen. Eleven patients had an abnormal diurnal variation, seven had an abnormal response to metyrapone, and eight had an abnormal response to dexamethasone. All who were given pyrogen reacted normally to this stress. Two patients who died had lesions in the anterior hypothalamus, and it is suggested that this localization of lesions was responsible for the pattern of pituitary–adrenal dysfunction which was observed. An improvement in function was seen in many patients after an interval of a month.
FEASIBILITY AND SAFETY OF OUTPATIENT CORONARY CT ANGIOGRAPHY FOR EMERGENCY DEPARTMENT PATIENTS WITH POTENTIAL ISCHEMIC CHEST PAIN
Authors: Rekha Raju, Frank Scheuermeyer, Stephen Choy, Giang Nguyen, Bruce Precious, Adam Berger, Brett Heilbron, Carolyn Taylor, Cameron Hague, Eric Grafstein, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2014)
Osteomyelitis and Hemodialysis
Authors: N. Lameire, M. Cardon, J. Hilderson, S. Ringoir
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 September 1973Osteomyelitis and HemodialysisN. LAMEIRE, M.D., M. CARDON, M.D., J. HILDERSON, M.D., S. RINGOIR, M.D., PH.D.N. LAMEIRE, M.D.Search for more papers by this author, M. CARDON, M.D.Search for more papers by this author, J. HILDERSON, M.D.Search for more papers by this author, S. RINGOIR, M.D., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-3-454_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe read with great interest the article in your May 1973 issue, "Osteomyelitis in Hemodialysis Patients," by Leonard and colleagues (Ann Intern Med 78:651-658, 1973). Five patients with this uncommon complication of chronic hemodialysis are described. Despite the frequency of bacterial infections, especially staphylococcal, such a complication has not previously been reported in hemodialysis patients. This prompts us to describe briefly another case of osteomyelitis recently observed in our dialysis unit.On 11 January 1973 a 42-year-old white man suffering from end-stage renal disease was admitted to our unit. After an emergency peritoneal dialysis, clinical study led to the diagnosis... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHost Defenses and Immunologic Alterations Associated with Chronic HemodialysisSIMEON E. GOLDBLUM, M.D., WILLIAM P. REED, M.D.Staphylococcus Aureus Bacteremia in Hemodialysis Patients 1 September 1973Volume 79, Issue 3Page: 454-455KeywordsMedical dialysisOsteomyelitisPeritoneal dialysisRenal failureStaphylococcal infection Issue Published: 1 September 1973 PDF DownloadLoading ...
The Role of Interferon in Cancer Therapy: A Current Perspective
Authors: D. Goldstein, J. Laszlo
Journal: CA A Cancer Journal for Clinicians (1988)

Recombinant interferon alpha has now been established as having a distinct if narrow role when used as a single agent in cancer therapy. The responses to single-agent therapy can be grouped as shown in Table 7. Interferon is likely to be the treatment of choice for hairy cell leukemia and possibly also for symptomatic nodular lymphoma. Interferon is very useful in treating papillomas and condylomas, and its role as a local agent will probably expand. The list of responding cancers for alpha interferon or other subtypes as a single agent is unlikely to expand greatly over the next few years. Nevertheless, in both melanoma and renal carcinoma, meaningful responses do occur. It is important to be aware of the possibility of both delayed and increasing extent of response with duration of treatment; adequate trials of interferon may therefore require longer periods of treatment than does conventional chemotherapy. Furthermore, because prior failure to respond to chemotherapy does not predict response to interferon, its use as a second-line agent should also be considered. The future of such biological agents, however, clearly lies in combination with other agents as the "fourth arm" of cancer therapy. The challenge is to define what the role of that fourth arm will be. There seems to be a clear choice with the interferons. They can be used at pharmacological doses, in which case their antiproliferative effect is likely to be due to induction of certain enzymes that result in a cytostatic effect in susceptible cancers, of which there are a limited but therapeutically important number. Alternatively, the interferons can be used at physiological doses, which are more likely to cause immunological and cell membrane effects such as NK-cell stimulation, as well as Fc-receptor and tumor-antigen expression. Thus, combination with cytotoxic agents may well require high doses, whereas combination with other biological agents, such as monoclonal antibodies or LAK cells, may be most effective at much lower doses. Over the next few years it will be important to establish the optimal biological doses of the interferons, so that we can maximize their usefulness in therapy and avoid the trap of thinking of them as purely cytotoxic agents.