tbuckley/cabot-search huggingface dataset:
Robustness of measles immunity in parturient women in Gipuzkoa, Basque Country, Spain, in the post-vaccination era
Authors: G Cilla, E Serrano-Bengoechea, D Vicente, M Montes, E Pérez-Trallero
Journal: Eurosurveillance (2007)

The infants of mothers with vaccine-induced immunity lose passive acquired measles antibodies earlier than infants of naturally infected mothers. This study included two cohorts of parturient women: one composed of women who gave birth in 1990 (end of the epidemic period), and another comprising women who gave birth in 2006 (after eight years without virus circulation). Immunoglobulin G (IgG) antibodies against measles (IgG-AM) were investigated by enzyme immunoassay in stored serum samples (-40 degrees C). Measles-IgG titres of >400 mIU/mL were found in all 185 parturient women who gave birth in 1990, all with natural immunity. Of 185 women who gave birth in 2006, most of whom had vaccine-induced protection, measles-IgG were undetectable in 4.9% (<150mIU/mL), values were borderline in 7% (150-299 mIU/mL), and the geometric mean titre was lower (p<0.001), being 3.4 to 3.8 times lower in women aged <28 years. The changing levels of maternal measles antibodies suggest that in Spain, the window of susceptibility to measles in infants is increasing. To protect susceptible infants against measles in countries with long-established vaccination programs where measles immunity in parturient women was artificially acquired, it is essential to ensure that both doses of the routine measles vaccine achieve a coverage of >95%, and that infants receive the first vaccination dose before 15 months of age (e.g. at 12 months).
Abstract 17578: Reductions in Systematic Inflammation After a Low-Carbohydrate Diet versus a Low-Fat Diet Each Combined with Exercise
Authors: Kerry J Stewart, Pamela Ouyang, Dhananjay Vaidya, Devon A Dobrosielski
Journal: Circulation (2012)

Background: Systemic inflammation is a mechanism by which obesity increases CVD risk. Though weight loss generally improves inflammation, a concern about low-carbohydrate (CHO) diets is that a conc...
Medicine must change to serve an ageing society
Authors: A. Tonks
Journal: BMJ (1999)

Doctors and those responsible for commissioning and shaping health services have failed to acknowledge the rapid ageing of most societies. This worldwide phenomena is unprecedented, leaving us ignorant, fearful, and reluctant to tackle it face on. A conference in London last month examined how medicine and its institutions must change to serve a growing older population while still meeting the needs of younger people. Two issues dominated: age discrimination and resources.

Currently 20% of the population of the United Kingdom is over 60-12 million people. By 2031 this proportion will be nearly a third—18.6 million people.1 Most will lead healthy and rewarding lives, but the numbers of people needing acute and long term care will inevitably increase. Rates of cardiovascular disease, dementia, and osteoarthritis among elderly people in the next century will be greatly determined by success or failure now in preventing such disease.

Health care is ill suited to perform well in a world with many more elderly people because it is ageist. Older people face arbitrary discrimination in their encounters with health professionals,2 and this probably reflects a wider ageism within society. Older …
NICE to reconsider evidence on interferon beta
Authors: Roger Dobson
Journal: BMJ (2000)

The National Institute for Clinical Excellence (NICE) is to reconsider the evidence for using interferon beta in the treatment of multiple sclerosis. The move follows an appeal against the provisional opinion of the appraisal committee of NICE that the drug had a modest clinical benefit outweighed by a high cost.

After the appeal hearing, the Multiple Sclerosis Society and Biogen, one of two drug makers who lodged appeals, said they were concerned about the length of time the evaluation had taken and the effects on patients. In its verdict, the NICE appeal panel said that the appraisal committee had not explained the basis …
Abstract 12040: Direct Reprogramming of Fibroblasts into Functional Endothelial Cells Capable of Enhancing Angiogenesis in Infarcted Tissues and Re-Endotheliulization in Vessel Grafts
Authors: Andriana Margariti, Bernhard Winkler, Eirini Karamariti, Tsung-neng Tsai, Lingfang Zeng, Yanhua Hu, Qingbo Xu
Journal: Circulation (2011)

Background - The generation of induced pluripotent stem (iPS) cells is a fascinated tool for regenerative medicine including cardiovascular tissues. However, the main restriction for iPS cell application is the risk of tumour development. Methods and Results - In this study we adapted a new method to generate partial-iPS (PiPS) cells by transferring four reprogramming factors (OCT4, SOX2, KLF4 and c-MYC) to human fibroblasts for short periods of time. PiPS cells did not form tumours in vivo, and have the potential to specifically differentiate into different cell lineages, such as neurons, adipocytes, osteocytes, chondrocytes as well as endothelial cells. The PiPS-derived endothelial cells expressed a panel of endothelial markers at gene and protein levels and they formed vascular tubes in vitro and in vivo Matrigel plaque assays. Data from a series of experiments indicate a novel gene SETSIP was crucial in endothelial cell differentiation. SETSIP was expressed in parallel with endothelial cell markers, a...
Detection of embolic particles with the Doppler guide wire during coronary intervention in patients with acute myocardial infarction
Authors: Atsunori Okamura, Hiroshi Ito, Katsuomi Iwakura, Shigeo Kawano, Koichi Inoue, Yoshihiro Maekawa, Toshio Ogihara, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2005)
Abstract 16014: Evaluation of Cardiac Events in ATLAS ACS 2-TIMI 51
Authors: Jessica L Mega, Eugene Braunwald, Stephen D Wiviott, Sabina Murphy, Alexei Plotnikov, Nina Gotcheva, Mikhail Ruda, C. Michael Gibson
Journal: Circulation (2012)

Introduction: The ATLAS ACS 2-TIMI 51 trial was designed to test two low doses of the factor Xa inhibitor rivaroxaban in patients with a recent ACS. Both doses reduced the primary efficacy endpoint...
Abstract 8640: Sudden Cardiac Death and Supraventricular Tachycardia Incidence in Patients with Asymptomatic Pre-excitation - A Meta-analysis
Authors: Manoj N Obeyesekere, Peter Leong-Sit, David Massel, Andrew D Krahn, Allan C Skanes, Lorne J Gula, Raymond Yee, George J Klein
Journal: Circulation (2011)

Background: The risk of sudden cardiac death (SCD) and management of this risk in patients with asymptomatic pre-excitation is controversial. The purpose of this meta-analysis was to define the incidence of SCD and supraventricular tachycardia (SVT) in patients with asymptomatic pre-excitation. Methods: We performed a systematic search of prospective, retrospective, randomized or cohort, English language studies in EMBASE and Medline to February 2011. Inclusion criteria were studies of asymptomatic patients with pre-excitation who did not undergo ablation. When studies reported on symptomatic patients and/or catheter ablation of asymptomatic patients, only asymptomatic patients who did not undergo catheter ablation were included. Incidence of SCD/aborted SCD and incidence of SVT were extracted and pooled using a DerSimonian-Laird random effects model and fixed effects model to construct 95% confidence intervals (CI). Heterogeneity analyses were performed. Results: Twenty-one studies involving 12096 person-years (PYrs) of follow-up met our inclusion criteria. Follow-up ranged from a mean of 15 months to 21.8 years. Participants were primarily male (weighted average 67%). Mean ages in the studies ranged from 7 to 43 years. The weighted mean age was 26.5 years. SCD episodes were reported in 7 studies with 4283 PYrs of follow-up. Rates of SCD ranged from 0.7 to 8 per 1000 PYrs. No events were seen in 14 studies with a total follow-up of 7813 PYrs. Considering all patients the unadjusted rate was 1.1 SCD events per 1000 PYrs. We found moderate evidence of statistical heterogeneity (p=0.064, I 2 34.2%). Using a fixed effects model the SCD risk was estimated at 1.0 (95% CI: 0.5 to 1.7) per 1000 PYrs. Using a random effects model the risk of SCD is estimated at 1.6 (95% CI: 0.7 to 2.6) per 1000 PYrs. The development of SVT was described as an outcome in 19 studies involving 10258 PYrs. Rates in individual studies varied from 0 to 50 events per 1000 PYrs. There was no statistical evidence of heterogeneity (p&lt;0.0001, I 2 85.3%). Using a random effects model, the overall risk of SVT was 18 (95% CI: 11 to 26) events per 1000 PYrs. Conclusions: The exceedingly low risk of SCD and low risk of SVT may argue for a conservative approach in managing patients with asymptomatic pre-excitation.
A Roadmap to Investigate the Genetic Basis of Bicuspid Aortic Valve and its Complications
Authors: Siddharth K. Prakash, Yohan Bossé, Jochen D. Muehlschlegel, Hector I. Michelena, Giuseppe Limongelli, Alessandro Della Corte, Francesca R. Pluchinotta, Maria Giovanna Russo, Artur Evangelista, D. Woodrow Benson, Simon C. Body, Dianna M. Milewicz
Journal: Journal of the American College of Cardiology (2014)
Abstract 362: Classification of Severe Left Ventricular Dysfunction Using Global Longitudinal Strain and Outcome
Authors: Tony Stanton, Rodel Leano, Thomas H Marwick
Journal: Circulation (2009)

Purpose:  The diagnosis of severe left ventricular dysfunction (LVD) has an significant adverse prognostic impact. We have previously shown a cut off of −12% global longitudinal strain(GLS) to be equivalent to EF   Methods:  We studied 546 consecutive individuals (64% male, age 60.9±11.9 years) undergoing echocardiography. EF was calculated using Simpson’s biplane. GLS was calculated using 2D speckle tracking as the mean GLS from 3 apical views. Outcome was expressed using Kaplan-Meier analysis and log-rank tested for significance. Individuals were followed for all-cause mortality for a mean of 5.2±1.5 years. There were 91 deaths.   Results:  Overall population mean EF was 57.6±2.1% and mean GLS −16.6±4.3%. 29 individuals (5.3%) had an EF −12%. These individuals also had significantly worse outcome compared to those with GLS≤ −12% (p −12% almost completely overlay each other as did the curves for EF≥35% and GLS≤ −12% indicating comparable prognostic outlooks for these groups (figure). Log rank testing showed there was no significant difference between the EF≥35% and GLS≤ −12% groups (p=0.6) and the EF≥35% and GLS≤ −12% groups (p=0.45).   Conclusion:  A global longitudinal strain cut off value of −12% has an almost identical prognostic influence as an ejection fraction
Abstract 1519: Atrial Fibrillation Is Independently Associated With A High Risk of Death in Patients With Acute Coronary Syndromes
Authors: Renato D Lopes, Kenneth Mahaffey, Robert A Harrington, John Horton, Paul Armstrong, Kristin Newby, Magnus Ohman, Frans Van de Werf, Sana M Al-Khatib, Lars Wallentin, Christopher B Granger
Journal: Circulation (2007)

Purpose: To assess whether atrial fibrillation (AF) is associated with 1-year mortality among patients with acute coronary syndromes (ACS). Methods: We analyzed the 1-year mortality of 110,588 ACS patients using a pooled database of clinical trials. Cox proportional hazards modeling was used to adjust for baseline characteristics including AF that may be associated with the risk of death within 7 days, and death from day 7 to 1 year. We examined the effect of AF in patients with ST-segment elevation versus those with non ST-segment elevation. Results: The prevalence of in-hospital AF was 8.0%. Baseline characteristics according to AF or not were: median age (70 vs 62 years), systolic blood pressure (130 vs 130mmHg), Killip class III and IV (4.2% vs 1.6%), history of hypertension (41% vs 48%), diabetes mellitus (19% vs 16%), prior congestive heart failure (7% vs 3.5%), and prior myocardial infarction (23% vs 20%). The figure shows the significant relationship of AF with mortality in the overall population. AF was significantly associated with an increased risk of in-hospital mortality in the non ST elevation ACS patients (adjusted odds ratio (OR) of 1.9 95% CI 1.5 to 2.5), but not in the ST elevation ACS patients (adjusted OR 1.0 95% CI 0.9 to 1.1). However, AF was significantly associated with an increased risk of death from day 7 to 1 year for both ST and non ST elevation ACS patients (adjusted OR 3.8 95% CI 3.5 to 4.1, and 2.2 95% CI 1.7 to 2.7, respectively). Conclusion: Among patients with ACS, AF is independently associated with a higher risk of 1-year mortality for both ST and non ST elevation ACS patients. Understanding the reasons for this increased risk may provide opportunity for improving care.
The Fas pathway contributes to the metastatic potential of osteosarcoma to the lungs
Authors: Nadezhda V. Koshkina, Eugenie S. Kleinerman
Journal: Cancer Research (2006)

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Fas and its ligand (FasL) are complementary receptor-ligand proteins that induce apoptosis in many cell types. Disregulation of the Fas mechanism has been implicated in tumor progression. However, how alterations in this mechanism affect metastatic activity of tumor cells remains unclear. Osteosarcoma (OS) is bone malignancy that metastasizes almost exclusively to lungs. Immunohistochemical (IHC) analysis of lung metastases from patients with OS and from our OS animal models showed negligible levels of Fas. We hypothesized that since FasL is constitutively expressed in the lungs, the lack of Fas receptor or corruption of the Fas-mediated pathway may be used by tumor cells to evade host-defense mechanism. To validate this hypothesis we sorted Fas-negative populations of mouse OS Dunn and Dunn LM8 (DLM8) cells, which have low and high incidence of lung metastases following s.c. injection, respectively. Approximately 70-80% of Dunn and DLM8 cells are Fas- under ambient in vitro conditions. Equal numbers of not-sorted cells (Fas) and their Fas-negative subpopulations (Fas-) were injected s.c. into syngenic C3H mice. We did not observe significant changes in the rate of s.c. tumor growth between Fas- and Fas cells. However, examination of animal lungs revealed that incidence of visible metastases in Fas- groups significantly increased, when compared with Fas groups for both Dunn and DLM8 cells. We also transfected mouse OS K7 cells, that express high levels of Fas and are sensitive to recombinant soluble FasL treatment in vitro , with FADD-dominant negative (FDN) plasmid that inhibits the Fas pathway. Three K7/FDN clones that became resistant to FasL treatment following FDN transfection were selected and injected i.v. into BALB/c mice. K7 cells that were not transfected or transfected with “empty” plasmid (K7/neo) were used as controls. Parental K7 cells have very low incidence of lung metastases, which are usually represented by few tumor lesions of microscopic size. Transfection of K7 cells with empty plasmid did not alter their metastatic property. In contrast, inhibition of Fas pathway in K7/FDN clones lead to significant increase of their metastases incidence and tumor burden in animal lungs. IHC staining of pulmonary metastases formed by K7/FDN clones showed increased levels of Fas expression, whereas metastases formed by K7 and K7/neo cells remained Fas-negative. These data indicate that during invasion of OS cells into the lungs, tumor cells are selected for the Fas, i.e. cells that express functional Fas receptor on their cell surface undergo apoptosis upon binding to FasL expressed in the lungs, in contrast, cells that lack Fas or have impaired Fas mechanism can survive and form lung metastases. Using different approaches and two different animal models we identified that Fas loss-of-function is sufficient for acquisition and may enforce the metastatic phenotype of OS tumor cells.
Abstract 1948: Over-expression of HSP27 Provides Chronic Atheroprotection: Reductions in Foam Cell Content and Inflammatory Responses
Authors: Yong-Xiang Chen, Katey Rayner, Paromita Deb-Rinker, Trevor Simard, Melissa McNulty, Xiaoling Zhao, Edward R O’Brien
Journal: Circulation (2008)

Introduction: Heat Shock Protein 27 (HSP27) was recently shown by our laboratory to be a biomarker of atherosclerosis and after 4 weeks of a high fat diet (HFD) apoE −/− mice that over-express HSP27 (or apoE −/− HSP27 o/e mice) show a marked attenuation of aortic lesion size compared to apoE −/− mice - but only in females (ATVB 20005; Circ Res in press). Moreover, we demonstrated that serum HSP27 levels were inversely related to atherosclerotic burden, estrogens mediated the release of HSP27 from cells and extracellular HSP27 bound to Scavenger Receptor-A where it could competitively inhibit acLDL uptake. Purpose/Methods: The goal of this study was to determine if and how HSP27 over-expression persistently attenuates atherogenesis in apoE −/− mice fed a HFD for 12 weeks. Results: Compared to female apoE −/− mice, female apoE −/− HSP27 o/e mice showed persistent reductions in aortic (en face) lesion area and aortic sinus cross-sectional lesion area at 12 weeks (e.g., 38% and 39% respectively vs. 35% and 40% after 4 weeks of HFD). Although our original studies revealed that male apoE −/− HSP27 o/e mice had no protection from atherogenesis after 4 weeks of a HFD, in the current study we noted that 12 weeks of a HFD resulted in a 17% reduction in aortic (en face) lesion area and a 24% attenuation in aortic sinus cross-sectional lesion area with HSP27 over-expression. While lesions observed after 4 weeks of HFD consisted mainly of lipid-laden foam macrophages, after 12 weeks of HFD the histopathology was different and included a distinct foam cell layer (or FCL) luminal to a deeper necrotic layer (e.g., with cholesterol crystals). The FCL area was reduced in size in apoE −/− HSP27 o/e vs. apoE −/− mice (e.g., −63% in females, p=0.03; and −48% in males, p=0.02). In vitro, macrophages from apoE −/− HSP27 o/e mice showed a reduction in TNF-α expression compared to apoE −/− mice (e.g., 40% at baseline, and 55% after LPS provocation). Conclusions: Over-expression of HSP27 provides a persistent atheroprotective effect that benefits both sexes. Chronic lesions are not only smaller in size with HSP27 over-expression but show fewer foam cells and macrophages are less pro-inflammatory. These results highlight a potential clinical role for chronic HSP27 modulation for atheroprotection.
Mucin 1 (MUC1) expression in patients (pts) with early stage non-small cell lung cancer (NSCLC): Relationship between immunohistochemistry (IHC), tumor characteristics, and survival.
Authors: Paul Leslie Mitchell, Shane Battye, Tom John, Carmel Murone, Simon Knight, Gerd Bode, Andreas Schroeder, Khashayar Asadi
Journal: Journal of Clinical Oncology (2013)

3011 Background: MUC1, a glycoprotein highly expressed in many malignancies, is being explored as an antigen for immunotherapy. How best to measure MUC1 expression as well as its prognostic value in NSCLC are still under discussion. Methods: TMAs were constructed using triplicate 1mm cores of FFPE tumour and stained with 214D4 (recognises protein core) and MA695 (recognises carbohydrate epitope) anti-MUC1 antibodies (abs). TMAs were assessed for polarisation, both cyto and mem staining intensity (scored 0-3) and proportion cells +ve (0-100%; scored 0–5), averaged for multiple cores. A composite score (intensity x cells +ve) was derived, ranging from 0–15 (3+ in &gt;75% cells). Results: TMAs from 521 pts were analysed: male 362 (69.5%); never smoking 35 (7%); adeno 259 (49.7%), squamous 180 (34.5%), large cell 39 (7.5%); nodal N0 340 (65.3%), N1 71 (13.6%), N2 107 (20.5%). Results of IHC staining intensity, proportion positive cells and depolarisation were very similar for the two abs. There was high concordance in the composite score for the abs (R 2 =0.71, p&lt;0.0001). Polarisation was discordant in 7.9% of cases. For 77 cases with paired primary/ N2 nodal tissue, mean 214D4 scores were 8.3 and 8.9 and MA695 10.6 and 9.9 respectively. Discordant staining in primary but not in node was seen in 5.2% and 10.4% with 214D4 and MA695 respectively. Increased expression as assessed by 214D4 (HR=1.26; 95% CI 1.014-1.565, p=0.04 log rank test) and MA695 (HR=1.20, 95% CI 1.042-1.605; p=0.02) was associated with improved survival. The prognostic value of depolarisation has yet to be analyzed. Conclusions: Over 93% of cases were MUC1 IHC positive. Composite scores for the 2 abs were highly correlated and depolarisation largely concordant. MUC1 expression was generally maintained in paired primary/nodal tumour. Increased expression of MUC1 was associated with improved survival however further investigation is needed to determine which abs best predict outcomes. [Table: see text]
Abstract 6168: Growth-Differentiation Factor-15 Is an Independent Prognostic Indicator in Idiopathic Pulmonary Arterial Hypertension
Authors: Tibor Kempf, Nils Nickel, Heike Tapken, Jorn Tongers, Florian Laenger, Ulrich Lehmann-Muehlenhoff, Heiko Golpon, Martin R Wilkins, J. Simon R Gibbs, Marius M Hoeper, Kai C Wollert
Journal: Circulation (2008)
Dutch life expectancy slips behind that of European neighbours
Authors: Tony Sheldon
Journal: BMJ (2001)

Holland is falling behind many of its European neighbours for life expectancy, and smoking seems to be the reason, says a study of mortality by the Netherlands National Institute of Public Health and the Environment (RIVM). The trend is particularly striking among Dutch women, who also have one of the highest rates of smoking in Europe.

In 1970, the average life expectancy of Dutch women was 76, the third highest in Europe, with only Swedish and Norwegian women living …
Oncogene-specific gene expression signature at preneoplastic stage defines distinct mechanisms of hepatocarcinogenesis in E2f1, c-Myc, and E2f1/c-Myc transgenic mice
Authors: Cedric Coulouarn, Luis Gomez-Quiroz, Ju-Seog Lee, Pal Kaposi-Novak, Elizabeth A. Conner, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2006)

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We applied a genome-wide microarray analysis to three transgenic mouse models of liver cancer in which targeted over-expression of either c-Myc , E2f1 , or their combination was driven by the albumin enhancer promoter. Although gene expression profiles in HCCs derived in all three transgenic lines were highly similar, oncogene-specific gene expression signatures were identified at an early dysplastic stage of hepatocarcinogenesis. Over-expression of E2f1 was associated with a strong alteration in lipid metabolism, and Srebp1 was identified as a candidate transcription factor responsible for lipogenic enzyme induction. The molecular signature of c-Myc over-expression included more than 60 genes involved in the translational machinery that correlated with an increase in liver mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced the expression of genes involved in mitochondrial metabolism, particularly the components of the respiratory chain and correlated with an increased ATP synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination promote liver tumor development by distinct mechanisms. Determination of tissue specific oncogenes gene expression signatures might be useful to identify conserved expression modules in human cancers.