tbuckley/cabot-search huggingface dataset:
Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events
Authors: John McMurray, R Holman, Steven Haffner, M Bethel, Bjoern Holzhauer, Tsushung Hua, Yuri Belenkov, Mitradev Boolell, John Buse, Brendan Buckley, Antonio Chacra, Fu-Tien Chiang, Bernard Charbonnel, Chun-Chung Chow, Melanie Davies, Prakash Deedwania, Peter Diem, Daniel Einhorn, Vivian Fonseca, Gregory Fulcher, Zbigniew Gaciong, Sonia Gaztambide, Thomas Giles, Edward Horton, Hasan Ilkova, Trond Jenssen, Steven Kahn, Henry Krum, Markku Laakso, Lawrence Leiter, Naomi Levitt, Viacheslav Mareev, Felipe Martinez, Chantal Masson, Theodore Mazzone, Eduardo Meaney, Richard Nesto, Changyu Pan, Rudolf Prager, Sotirios Raptis, Guy Rutten, Herbert Sandstroem, Frank Schaper, Andre Scheen, Ole Schmitz, Isaac Sinay, Vladimir Soska, Steen Stender, Gyula Tamas, Gianni Tognoni, Jaakko Tuomilehto, Alberto Villamil, Juraj Vozar, Robert Califf
Journal: New England Journal of Medicine (2010)

It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance.In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization.The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85).Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)
Proposed recommendations for the management of HIV post-exposure prophylaxis after sexual, injecting drug or other exposures in Europe
Authors: J Almeda, J Casabona Barbarà, B Simon, M Gérard, D Rey, V Puro, T Thomas
Journal: Eurosurveillance (2004)

Post-exposure prophylaxis (PEP) is the standard of care for a healthcare worker (HCW) accidentally exposed to an HIV infected source person (occupational exposure), but this is not the case for non-occupational exposures. Very few national guidelines exist for the management of non-occupational exposures to HIV in Europe, contrarily to the occupational ones. The administration of non-occupational post-exposure prophylaxis (NONOPEP) for HIV may be justified by: a biological plausibility, the effectiveness of PEP in animal studies and occupational exposures in humans, efficacy in the prevention of mother to child HIV transmission, and cost effectiveness studies. These evidences, the similar risk of HIV transmission for certain non-occupational exposures to occupational ones, and the conflicting information about attitudes and practices among physicians on NONOPEP led to the proposal of these European recommendations. Participant members of the European project on HIV NONOPEP, funded by the European Commission, and acknowledged as experts in bloodborne pathogen transmission and prevention, met from December 2000 to December 2002 at three formal meetings and a two day workshop for a literature review on risk exposure assessment and the development of the European recommendations for the management of HIV NONOPEP. NONOPEP is recommended in unprotected receptive anal sex and needle or syringe exchange when the source person is known as HIV positive or from a population group with high HIV prevalence. Any combination of drugs available for HIV infected patients can be used as PEP and the simplest and least toxic regimens are to be preferred. PEP should be given within 72 hours from the time of exposure, starting as early as possible and lasting four weeks. All patients should receive medical evaluation including HIV antibody tests, drug toxicity monitoring and counseling periodically for at least 6 months after the exposure. NONOPEP seems to be a both feasible and frequent clinical practice in Europe. Recommendations for its management have been achieved by consensus, but some remain controversial, and they should be updated periodically. NONOPEP should never be considered as a primary prevention strategy and the final decision for prescription must be made on the basis of the patient-physician relationship. Finally, a surveillance system for these cases will be useful to monitor NONOPEP practices in Europe.
Long-Term Clinical Benefit of Sirolimus-Eluting Stents in Patients With In-Stent Restenosis
Authors: Fernando Alfonso, María-José Pérez-Vizcayno, Rosana Hernández, Armando Bethencourt, Vicens Martí, José R. López-Mínguez, Juan Angel, Andrés Iñiguez, César Morís, Angel Cequier, Manel Sabaté, Javier Escaned, Pilar Jiménez-Quevedo, Camino Bañuelos, Alfonso Suárez, Carlos Macaya
Journal: Journal of the American College of Cardiology (2008)
<i>RAS</i> Mutations in Colorectal Cancer
Authors: Yu Sunakawa, Heinz-Josef Lenz, Wataru Ichikawa
Journal: New England Journal of Medicine (2013)

mu-tations in exon 2 could predict a lack of response in patients who received panitumumab plus oxali -platin, fluorouracil, and leucovorin (FOLFOX4) for the treatment of metastatic colorectal cancer. The grade of rash in patients who received an anti–epidermal growth factor receptor antibody has been strongly associated with clinical out-come, even in patients who have
CD6 Ligation Modulates the Bcl-2/Bax Ratio and Protects Chronic Lymphocytic Leukemia B Cells From Apoptosis Induced by Anti-IgM
Authors: Lyda M. Osorio, Angelina De Santiago, Miguel Aguilar-SantelisesHå, kan Mellstedt, Mikael Jondal
Journal: Blood (1997)
Abstract P420: Healthcare Providers as Role Models for Physical Activity
Authors: Isabel Garcia de Quevedo, Felipe Lobelo
Journal: Circulation (2013)

Background. Health care providers (HCPs) are in a privileged position to give credible advice on healthy lifestyles, including physical activity (PA) promotion, a national public health objective (Healthy People 2020). It has been reported that HCPs own habits matter in their counseling practices. Active HCPs that comply with PA guidelines are more likely to counsel and give more motivating PA advice to their patients. Objectives. The purpose of this literature review was to summarize the evidence on the association between HCPs personal PA habits and their related counseling practices on PA Methods. Search terms such as “attitudes”, “habits”, “health personnel", "physical activity", “exercise", and “role model” were used to identify relevant articles. On-topic articles were retrieved and a snow ball literature search methodology was used to select the most relevant articles in PubMed between 1979 and 2012. Articles were hand-picked and organized by type: observational vs intervention. Results. A total of 196 articles were retrieved: 23 were descriptive studies of HCP habits or counseling, and 28 studies (24 observational and 4 interventions) suggested HCPs personal PA habits influence their counseling behavior and attitudes towards PA. The majority of studies were from the US (n=21). Seven included non-physician population (nurses, pharmacists and other HCPs). The most frequent PA assessment method was self-reported questionnaires. For counseling behaviors, studies measured perceived frequency or self-efficacy for their practice. All but one of the 24 observational studies found significant associations between HCPs personal PA or fitness levels and the behaviors towards related PA counseling. This association was observed among physicians (n=15) and non-physicians (n=6) and also among medical (n=6) and nursing (n=1) students. Four observational studies reported physicians PA to be an independent effect for counseling (OR = 5.72, 3.4, 3.2, 1.1, 2.44 p &lt; 0.05). Three studies showed a significant correlation between PA habits of HCP and their perceived frequency for counseling (r = 0.25 - 0.37). Among the 4 interventions found, only one focused on improving medical students’ PA habits and reported a significant association between improved physicians’ PA levels and counseling (OR 1.56 CI 1.04, 2.34; p= 0.03). Conclusion. HCPs own PA habits are an independent predictor of PA counseling practices. Interventions to improve HCPs PA habits have the potential to also improve HCPs PA counseling to patients. More research is needed in particular among non-physician populations and in low-to-middle income countries settings where the burden of inactivity is greatest.
Abstract 290: Constitutional BRCA1 methylation is a major predisposition factor for high-grade serous ovarian cancer
Authors: Alexander Dobrovic, Thomas Mikeska, Kathryn Alsop, Ida Candiloro, Joshy George, Gillian Mitchell, David Bowtell
Journal: Cancer Research (2014)

Abstract This study aimed to determine whether constitutional methylation of the BRCA1 promoter region was a predisposition factor for ovarian cancer. We had previously shown that in a case control study of early-onset breast cancer patients, the presence of constitutional BRCA1 methylation in the blood was associated with tumors that phenocopied pathogenic germline BRCA1 mutations, indicating that BRCA1 methylation predisposed to and drove the development of these tumors. Germline BRCA1 mutations also predispose to ovarian cancer, in particular, high-grade serous ovarian cancer. In collaboration with the Australian Ovarian Cancer Study, we determined the presence of detectable BRCA1 methylation in 154 high-grade serous cancers. Twenty patients showed detectable levels of BRCA1 methylation in DNA extracted from their peripheral blood. Remarkably, when the corresponding tumor samples were assessed for methylation, 14 of the 20 that showed any methylation corresponded to a highly methylated tumour. When tumors occurring before the age of 55 were considered, 9 of the 10 bloods with detectable mutation corresponded to a strongly methylated tumour. This study also determined the frequency of BRCA1 and BRCA2 mutations. Fifteen women had germline BRCA1 mutations and 11 had germline BRCA2 mutations. The germline BRCA1 mutation carriers were predominantly younger at diagnosis and 11 pathogenic BRCA1 mutations were seen in the under 55 group. BRCA1 methylation was mutually exclusive with BRCA1 mutation. This data strongly suggests that constitutional BRCA1 methylation can drive ovarian cancer, in particular early onset ovarian cancer, and moreover is as important a predisposition factor as BRCA1 mutation. Citation Format: Alexander Dobrovic, Thomas Mikeska, Kathryn Alsop, Ida Candiloro, Joshy George, Gillian Mitchell, David Bowtell. Constitutional BRCA1 methylation is a major predisposition factor for high-grade serous ovarian 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 290. doi:10.1158/1538-7445.AM2014-290
Book: Health, Civilization and the State: A History of Public Health From Ancient to Modern Times
Authors: J. P Mackenbach
Journal: BMJ (1999)

Dorothy Porter Routledge, £16.99, pp 376 ISBN 0 415 20036 9 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> How boring is the history of public health? As Dorothy Porter notes in her introduction, the subject tends to provoke a big yawn, both from students, who are bored by accounts of bureaucratic and technological reforms, and from historians, who are bored by the usual grand narrative of progress. Because historians don't write these histories any longer, George Rosen's A History of Public Health , originally published in 1958, is still widely used and recently reappeared in an updated and expanded version. But here we are, faced with a new history of public health "from ancient to modern times" written by a modern historian. Porter acknowledges the "contemporary intellectual climate of postmodernist relativism" and apologises for … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Erythromycin for Gastric Emptying in Patients Undergoing General Anesthesia for Emergency Surgery
Authors: Christoph Czarnetzki, Nadia Elia, Jean-Louis Frossard, Emiliano Giostra, Laurent Spahr, Jean-Luc Waeber, Gordana Pavlovic, Christopher Lysakowski, Martin R. Tramèr
Journal: JAMA Surgery (2015)

Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties.To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery.The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis.Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours.The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content.A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia.In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery.ClinicalTrials.gov identifier: NCT00827216.
The review body's remit should not be changed More women hold top NHS jobs NHS helpline will cover 10 million people BMA Notice
Authors: E M Armstrong
Journal: BMJ (1998)

# The review body's remit should not be changed {#article-title-2}

GPs have reacted strongly to what they see as a unilateral change in the remit of the doctors' and dentists' review body. At its first meeting last week the General Practitioners Committee (GPC) (formerly the General Medical Services Committee) was annoyed that the profession was being used as a regulator of the economy.

Following the comprehensive spending review (p 231) the review bodies have been told that in future their recommendations should take into account the service improvements that the government wants to achieve, the resources available to the NHS, and the government's inflation target, as well as recruitment and retention. In future the review bodies will report to departmental ministers and not the prime minister. In a letter to the review body chairmen, the prime minister said that he remained committed to the review body system and valued the independent advice received.

The chairman of council, Dr Ian Bogle, told the GPC that he planned to meet the chairman of the doctors' review body. Last year the review body …
ER stress upregulates the fatty acid synthesis pathway: implications for anti-tumor therapy
Authors: Joy Little, Frances Wheeler, Diane Fels, Constantinos Koumenis, Steven Kridel
Journal: Cancer Research (2007)

4484   Fatty Acid Synthase (FAS) is the terminal enzyme responsible for fatty acid synthesis and is upregulated in tumors of various origins to facilitate growth and progression. The strong link between FAS activity and tumor cell survival establishes FAS as an important target for anti-tumor therapy. We have recently demonstrated that FAS inhibitors interfere with ER homeostasis thereby activating the unfolded protein response (UPR). Because of this and a body of literature linking phospholipid and sterol levels to the UPR, we wanted to further investigate the link between ER stress and the fatty acid synthesis pathway. ER stress has a significant impact on fatty acid synthesis. Interesting, treatment of prostate cancer cells with Velcade (bortezimib, PS-341), the FDA approved proteasome inhibitor that has been shown to activate the UPR, leads to upregulation of fatty acid synthesis in a dose dependent manner. We hypothesize that this upregulation of fatty acid synthesis may be induced as a protective measure, consequently sensitizing tumor cells to FAS inhibition. Therefore, we asked whether the combination of Velcade and either C75 or orlistat would result in a synergistic cell death in prostate tumor cells. Indeed, low doses of Velcade combine with low doses of either orlistat or C75 to reduce clonogenic survival beyond that with either agent alone. This decrease in clonogenic survival is consistent with an increase in caspase 3 and PARP cleavage and coincides with a decrease in eIF2α phosphorylation that indicates proteotoxicity. Velcade may induce GADD34-mediated feedback that drives tumor cells past their ability to adapt when further stressed by inhibiting FAS. Collectively, these data support our novel observation regarding the link between ER homeostasis and FAS, as well as provide critical understanding towards how the UPR may be exploited for anti-tumor therapy and towards developing FAS inhibitors for clinical use.
Praevalence of pulmonary arterial hypertension in the HIV cohort of the University Bonn: Results of the PAHIBO study
Authors: Stefan Pabst, Christoph Hammerstingl, Carolynne Schwarze-Zander, Julia Ohlig, Tabea Nussbaum, Georg Nickenig, Juergen Rockstroh, Dirk Skowasch
Journal: European Respiratory Journal (2011)

Background:  PAH (pulmonary arterial hypertension) is a rare and life-threatening complication of HIV (human immunodeficiency virus) infection. An investigation of the presence of HIV infection is a standard diagnosis in patients with unexplained PAH. Previous studies suggest a prevalence of PAH in HIV patients close to about 0.5%, but are limited in the study design. Therefore the exact prevalence is unclear.   Methods:  The PAHIBO study is investigating all HIV patients (n = 700) at the University Hospital of Bonn in a prospective cross-sectional study. If systolic pulmonary arterial pressure (sPAP) is > 35 mmHg in Doppler echocardiography, right heart catheterization is followed.   Results:  To date, 340 patients were enrolled, 44/340 (13%) had an echocardiographic sPAP > 35 mm Hg. The right heart catheterization was carried out so far in 22/44 patients with echocardiographically proven PH. In 4 cases, a precapillary PAH (including a complete work-up and exclusion of other causes of PAH) was diagnosed, of which 1 case was already known, in 13 cases postcapillary PH and in the remaining 5 cases, the exclusion of a manifest PH. Thus, the PAHIBO study reveals a prevalence of HIV-associated PAH of at least 4/340 cases (1.2%).   Conclusion:  The prevalence of HIV-associated PAH is probably higher than previously described. Severe cardiac and respiratory comorbidities are very frequent in the examined HIV cohort. If these results should be confirmed in the extended cohort of 700 patients, a regular echocardiographic screening in asymptomatic HIV patients is to discuss.
Down‐regulation of natural killer cell activity by autologous polymorphonuclear leucocytes
Authors: B. K. Pedersen, A. Kharazmi, M. Svenson
Journal: Allergy (1988)

It has been recently reported that neutrophils are involved in the regulation of NK cell activity. However, the mechanism of such regulation is unclear. The present study was designed to investigate the mechanisms involved in the regulation of NK cytotoxicity by human neutrophils. The role of indomethacin, an anti‐inflammatory drug, in this interaction was studied. NK cells were purified from peripheral blood obtained from normal individuals. NK cell cytotoxicity was tested on K 562 cell line by Cr release assay, Autologous neutrophils obtained from peripheral blood were stimulated by opsonized zymosan either in the presence or absence of indomethacin. The role of neutrophil supernatant containing oxygen radicals and prostaglandins on NK cytotoxicity was examined. It was shown that supernatants from stimulated neutrophils significantly inhibited ( P &lt; 0.05) the autologous NK cell cytotoxicity. The presence of indomethacin in the in vitro reaction mixture, or given orally to donors, partially or completely abolished the inhibitory effect of neutrophil supernatant. Indomethacin inhibited prostaglandin E2 release, and luminol‐enhanced, myeloperoxidase‐mediated chemiluminescence of activated PMN. Diafiltration of neutrophil supernatant showed that the inhibitory activity was present in the fraction containing molecules lower than 5,000 daltons. In conclusion, our findings indicate that down‐regulation of NK cytotoxicity is mediated by prostaglandins produced by stimulated neutrophils and possibly by oxygen radicals.