tbuckley/cabot-search huggingface dataset:
Persistent high stroke mortality in Bangladeshi populations
Authors: Raj Bhopal, Taslin Rahemtulla, Aziz Sheikh
Journal: BMJ (2005)

Novel hypotheses to explain this need testing urgently 

Censuses in 1981, 1991,1–3 and 2001 (Wild et al. Persistence of substantial inequalities in cardiovascular disease mortality by country of birth in England and Wales 2001-2003. Unpublished manuscript). have shown that, among Bangladeshi-born men living in the United Kingdom, the standardised mortality ratio for stroke is two to three times the population average, with less marked but important excesses in Bangladeshi-born women. There has been little progress in understanding the reasons for this variation, let alone in identifying approaches to improve outcomes. Lessons learnt about stroke among British Bangladeshis may well apply to other populations at high risk, including Indians and Pakistanis, whose excess stroke mortality is not quite so high. In addition, such evidence could be highly relevant to reducing health inequalities.

Is the excess mortality from stroke in Bangladeshis explained by a higher case fatality ratio? Interim analysis of data from the south London stroke register shows no age adjusted difference in survival between Bangladeshis and white …
Clinical cure rates in patients treated with azithromycin (AZ) for lower respiratory infections (LRTI) caused by AZ-susceptible (AZ-S) and AZ-resistant (AZ-R) organisms: Analysis of phase 3 clinical trials
Authors: Alan Kaplan, George Zhanel, Christina Calciu, Wolter Kevin
Journal: European Respiratory Journal (2014)

Introduction: LRTI are commonly seen in respiratory medicine and include both exacerbations of COPD and community acquired pneumonia. They are often empirically treated with macrolides such as AZ. Resistance rates to macrolides are rising in many parts of the world.  Aim: The aim was to determine cure rates in AZ-treated patients with LRTI due to AZ-S and AZ-R organisms in randomized clinical trials (RCT).  Methods: 543 patients received AZ in 9 Phase 3 RCTs (1993-2007). Low-level AZ resistance (LLAR) was AZ MIC ≤8 μg/ml; high-level AZ resistance (HLAR) was AZ MIC ≥16μg/ml.  Results: 543 LRTI patients had 718 isolates; 174 had an AZ-R organism; 131 had ≥2 pathogens. Cure rates were: 93.4% (507/543) for all LRTI patients; 95.4% (352/369) for AZ-S patients; 89.1% (155/174) for AZ-R patients; 90.7% (97/107) for LLAR and 86.6% (58/67) for HLAR isolates; and 93.9% (123/131) in patients with multiple isolates.  Conclusion: AZ cure rates were higher in patients with only AZ-S isolates (95.4%) vs ≥1 AZ-R isolates (89.1%); p=0.006. However, interestingly, no difference was observed for LLAR vs HLAR (p=0.40). AZ is actually an azalide, and is concentrated within lysosomes within circulating white blood cells. Thus serum is not the reservoir supplying tissues and this may underlie the weak relationship between MIC and cure rate. Despite rising resistance to AZ, cure rates are still substantial allowing empirical treatment with AZ to be appropriate for many patients with LRTI.
Alteplase for stroke: money and optimistic claims buttress the "brain attack" campaign * Commentary: Who pays the guideline writers? * Commentary: Thrombolysis in stroke: it works!
Authors: J. Lenzer
Journal: BMJ (2002)

# Alteplase for stroke: money and optimistic claims buttress the "brain attack" campaign {#article-title-2} Both doctors and the public are becoming more alert to potential conflicts of interest, and an increasing number of journals now require competing interest statements from their authors and reviewers. In this article Jeanne Lenzer uses the example of guidelines produced by the American Heart Association to discuss some of the questions that can arise when interests conflict As doctors and the public become more aware of conflicts of interest involving study bias,1 publication bias,2 and industry gift giving3 they turn to credible non-profit organisations for sound medical recommendations. Unfortunately, many groups (and their individual panellists) that serve as arbiters of inconclusive data may also suffer from conflicts of interest. 4 5 One such conflict is self referencing bias. An example of this is in specialty guidelines for colon cancer screening, where radiologists recommend barium enemas while gastroenterologists recommend colonoscopy. A more important conflict arises when corporations with a financial stake in the recommendations issued by a non-profit making organisation provide financial support for that organisation. In this paper I examine an example of such a conflict, in which a treatment recommendation that could cost more lives than the disease itself was supported by statistics from only one randomised controlled study. Additionally, poor outcomes and dissenting opinion appear to have been obscured. This recommendation may have been made in a true spirit of unbiased scientific inquiry, but the appearance of dispassionate analysis was eroded by large donations from a drug company to the organisation making the recommendation and payments for research and lecture fees to its individual expert panellists. #### Summary points The American Heart Association rated the thrombolytic agent alteplase (tPA) as a class I (definitely recommended) intervention for stroke despite controversy about its safety and efficacy Most of the association's stroke experts have ties to the manufacturers of … Correspondence to: Dr Starkman
653. Activation of an ATM/chk2-Dependent Pathway Is Required for HSV-1 Protein ICp0 Induced G2/M Cell Cycle Arrest
Authors: Han Li, Joseph C. Glorioso
Journal: Molecular Therapy (2004)

Herpes simplex virus type 1 (HSV-1) replication involves the expression of its genes in a interdependent and well ordered cascade. The immediate early (IE) genes are expressed first on viral DNA entry into the nucleus and do not require expression of any other viral functions. The IE gene product, ICP0, plays an important role in enhancing early and late gene expression and is required for virus reactivation from latency in peripheral nerves. ICP0 is also toxic for dividing cells primarily through its ability to induce cell cycle arrest at G1 and S in synchronized cells and G2/M arrest in nonsynchronized cells ( ). The mechanism of cell cycle arrest is unknown. In this report, we confirm that mutant viruses that only express ICP0 cause G2/M arrest. Following infection, ICP0 induces ATM phosphorylation at tyrosine 1981 and CHK2 phosphorylation at tyrosine 68, P53 phosphorylated in serine 15 and 20. These events lead to G2 arrest. Chk2-/- cells can not cause G2/M arrest after virus infection but rather results in apoptosis. Together these results provide a mechanism through which ICP0 arrests cell division an event important to efficient virus growth.
Abstract 16519: Impaired Cardiac Sympathetic Innervation is Associated With Microvascular Dysfunction in Non-Infarcted Remote Myocardium in Ischemic- and Dilated Cardiomyopathy
Authors: Mischa T Rijnierse, Stefan de Haan, Hendrik J Harms, Marc Huisman, LiNa Wu, Aernout M Beek, Albert C van Rossum, Adriaan A Lammertsma, Cornelis P Allaart, Paul Knaapen
Journal: Circulation (2014)

Background:  Sympathetic denervation resulting from myocardial infarction is associated with sudden cardiac death. In addition, impaired sympathetic innervation in non-infarcted remote myocardium in ischemic and dilated cardiomyopathy (ICMP and DCMP) has been observed. Little is known about factors affecting sympathetic innervation in remote myocardium. The aim of this study was to assess the relation of positron emission tomography (PET) quantified sympathetic innervation and hyperemic myocardial blood flow (MBF) in non-infarcted remote myocardium in ICMP and DCMP patients.   Hypothesis:  As sympathetic nerves are highly susceptible to ischemia, we hypothesized that subtle perfusion abnormalities due to microvascular dysfunction may be related with sympathetic nerve integrity in non-infarcted myocardium.   Methods:  Seventy patients with ICMP or DCMP and left ventricular ejection fraction (LVEF) ≤35% were included (57 men, age 66 ± 9 years, LVEF 28 ± 7%, 52 ICMP). [ 15 O]H 2 O- and [ 11 C]Hydroxyephedrine (HED) - PET was performed to assess resting MBF, hyperemic MBF, and sympathetic innervation. Late gadolinium enhanced-cardiac magnetic resonance (LGE-CMR) imaging was performed to assess left ventricular end-systolic volume (LVESV), end-diastolic volume (LVEDV), and scar size. HED retention index (RI) and MBF were quantified in remote segments without scar, selected on LGE-CMR results.   Results:  [ 11 C]HED RI was significantly correlated with resting MBF (r=0.41, p 11 C]HED RI. Multivariable linear regression analysis revealed that hyperemic MBF ( B =0.87, p B =-0.04, p=0.001) were independent predictors for [ 11 C]HED RI in remote myocardium (R 2 =0.41).   Conclusion:  Hyperemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with both ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperemic MBF is the primary cause of this relation remains unclear.
Abstract 12019: Differential Effect of Ticagrelor versus Clopidogrel on Coronary Microvascular Function in Patients With Coronary Aertery Disease
Authors: Woong Gil Choi
Journal: Circulation (2014)

Introduction: Differential Effect of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function in Patients with Coronary Aertery Disease Background and Objectives: Ticagrelor is a new antiplatelet drug directly blocking P2Y12-adenosine diphosphate (ADP) receptors, which show a better clinical profile compared to clopidogrel in patients with acute coronary syndrome. Ticagrelor inhibits adenosine reuptake and increases coronary blood flow by a direct dilation of the microcirculation. We aimed to evaluate the effect of ticagrelor on coronary mircrovascular function in patient with coronary artery disease (CAD) in comparison with clopidogrel. Subjects and Methods: Twenty four patient with CAD were randomized to receive a single dose of ticagrelor (180 mg) or clopidogrel (300mg or on treatment state). Coronary microvascular function was invasively measured by using the index of microvascular resistance (IMR) and coronary flow reserve (CFR). The IMR was calculated from the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit time (hTmn). The CFR was calculated dividing the hTmn by baseline mean transit time. Results: There were no significant differences in baseline clinical and angiographic characteristics.CFR was not significantly different in both groups. (median: 4.00 [interquartile range(IQR) 2.30 to 4.92] vs 5.10 [IQR: 3.72 to 7.90], p = 0.24) However, IMR was significantly lower in ticagrelor than clopidogrel treated patients at 140 μg/kg per minute adenosine infusion rate. (median: 10.74 [interquartile range (IQR) 8.02 to 12.31] vs 15.56 [IQR: 10.77 to 29.74], p =0.05). Conclusions: In patients with CAD, ticagrelor might improves coronary microvascular functionel. These results suggest that ticagrelor could contribute to better clinical outcomes in CAD patients.
131. Cell-Targeting Ligand Discovery Using Context-Specific Phage-Presenting Peptide Libraries
Authors: Debadyuti Ghosh, Michael A. Barry
Journal: Molecular Therapy (2004)

Adenoviruses (Ad) have been developed as potential gene delivery vectors due to their ability to efficiently transduce a wide variety of dividing and non-dividing cells. However, the success of Ad vectors in vivo is limited in part by their promiscuous tropism for many non-specific cells. Retargeting approaches have been developed to improve Ad specificity. Previous work has shown ligands genetically engineered into surface exposed regions of the Ad capsid can redirect targeting. While this approach can work, in many cases inserted ligands fail to target when displayed in the different structural context of the viral protein. Conversely, insertion of even small peptides can destroy capsid function and the ability to assemble the virus.
Abstract P106: Physical Activity and Atrial Fibrillation in NHANES III
Authors: Larisa G Tereshchenko, Amit Shah, Elsayed Z Soliman
Journal: Circulation (2015)

Background: The impact of physical activity (PA) on the risk of atrial fibrillation (AF) is complex and controversial. The goal of this study was to examine the cross-sectional relationships between PA and AF in the Third National Health and Nutrition Examination Survey (NHANES III).

Methods: Self-reported type and level of PA was evaluated in 19,620 NHANES III participants (mean age 47.3±20.7y; 47% men; 42.0% non-Hispanic white, 27.6% non-Hispanic black, 26.6% Hispanics). We defined prevalent AF via ECG or by the presence of an irregular radial pulse palpated during physical examination in those excluded from ECG examination (suspected AF was an exclusion criteria for ECG). Logistic regression was adjusted for demographics (age, sex, and race), history of cardiovascular disease (heart attack, stroke and heart failure), and cardiovascular risk factors (diabetes, hypertension, hypercholesterolemia, and smoking).

Results: Presumed AF was found in 1191 participant (6.07%). AF prevalence was higher in participants who felt being less active (n=365, 8.2%) as compared to those who felt the same (n=497, 5.5%) or more active (n=329, 5.4%) than most men/women of the same age (Chi square P<0.0001). Feeling of being more active compared with most men/women of the same age was associated with a lower rate of AF (OR 0.78; 95%CI 0.72-0.84; P<0.0001). However, feeling of being more active compared with ten years ago was not associated with AF (OR 1.01; 95%CI 0.91-1.12); P=0.888). Doing gardening or yard work was associated with lower prevalence of AF (OR 0.58; 95%CI 0.51-0.66; P<0.0001), whereas running or jogging was associated with higher AF prevalence (OR 1.27; 95% 1.05-1.53; P=0.013). Bicycling, swimming, aerobics, dancing, calisthenics, and weight lifting did not have a significant association with AF. No interaction of PA with age, sex, or race was observed.

Conclusion: Low-intensity leisure PA and high perceived personal PA compared to age/sex matched peers are associated with lower prevalence of AF in a large sample of the adult United States population. These results could have potential implications on the types of physical activity recommended for individuals at risk of AF.
The predictive value of quantitative nailfold capillary microscopy in patients with undifferentiated connective tissue disease
Authors: None Ohtsuka, None Tamura, None Yamakage, None Yamazaki
Journal: British Journal of Dermatology (1998)

The present prospective study was undertaken to follow the natural history of patients with Raynaud's phenomenon and to document in these patients the frequency with which secondary disorders develop. Seventeen patients with primary Raynaud's phenomenon (PRP) and 43 patients with undifferentiated connective tissue disease (UCTD) were examined after 6–8 years to see whether they had developed into UCTD or systemic sclerosis (SSc), respectively. Their nailfold capillary parameters were analysed statistically to ascertain whether they would predict for the development of the diseases into UCTD or SSc. Two patients with PRP(12%) developed into UCTD, and 10 patients with UCTD (23%) into SSc. In PRP, all three parameters of the patients who developed into UCTD showed a tendency to be larger than in those who did not develop UCTD. In UCTD, the apical limb width (P < 0.02), capillary width (P < 0.01) and capillary length (P < 0.01) of the subjects who developed SSc were significantly larger than those who did not. Of the clinicolaboratory findings in patients with UCTD, the occurrence rate of abnormal apical limb width (relative risk 20.7, P < 0.01), abnormal capillary width (relative risk 10.7, P < 0.01), abnormal capillary length (relative risk 9.2, P < 0.02) and antinuclear antibody (relative risk 9.6, P < 0.05) showed a significant predictive value for the development of UCTD into SSc. These results indicate that quantitative nailfold capillary microscopy, as well as antinuclear antibody, will provide exact predictive information in patients with UCTD in clinical practice.
Mediterranean diet and the French paradox Two distinct biogeographic concepts for one consolidated scientific theory on the role of nutrition in coronary heart disease
Authors: Michel de Lorgeril, Patricia Salen, François Paillard, François Laporte, François Boucher, Joël de Leiris
Journal: Cardiovascular Research (2002)

the Seven Countries Study included an amount of alpha-Portugal 108 52 linolenic acid (the main plant n-3 fatty acid) three times as Greece 132 58 high as that of the Dutch cohort [19].Simopoulos showed
Abstract 282: Postresuscitation Care in a Quaternary Intensive Care Unit
Authors: Hannah F O’Regan, Peter Morley
Journal: Circulation (2014)

Objectives:  To identify factors associated with survival to hospital discharge admission to intensive care after cardiac arrest in 2014.   Methods:  Patients with cardiac arrest admitted to an Intensive Care Unit (ICU) from December 2013 to May 2014 were followed throughout their hospital admission. Demographic information and key factors known to impact outcomes were extracted from patient records. The primary endpoint was survival to hospital discharge, and the secondary endpoint was neurological outcome as assessed by cerebral performance category (CPC).   Results:  Fifty-five patients were admitted to the Intensive Care Unit at Royal Melbourne Hospital between December 2013 and May 2014. Out-of-hospital cardiac arrests accounted for 36/55 (65%) of the patients. Overall survival to hospital discharge was 27/55 (49%, 95%CI 35-63%), with 23/27 (85%, 71-100%) of survivors having a good neurological outcome (defined as CPC 1 or 2) at discharge. The initial rhythm was shockable in 20/55 (36%, 23-49%). The median time to CPR was 1 (Inter-Quartile Range 0-5) minute and the total time from arrest to Return of Spontaneous Circulation was 19 (10-31) minutes.  Arrest factors associated with improved survival included: an initial shockable rhythm (OR 14.17, 95%CI 3.39-59.19), female gender (OR 4.98, 1.36-18.21), witnessed arrest (OR 4.44, 1.08-18.53), and shorter time from arrest to ROSC (p   Conclusions:  Approximately half the patients who reach ICU alive after in- and out-of-hospital cardiac arrests survive neurologically intact to hospital discharge. Careful post-resuscitation management appears to improve survival.
Abstract 5000: The functional stem cell marker aldehyde dehydrogenase enhances pancreatic cancer stem cell isolation and correlates with clinical prognosis
Authors: Zeshaan A Rasheed, Jie Yang, Qiuju Wang, Irwin Freed, Jan-Bart Koorstra, Seung-Mo Hong, Xiaobing He, David Berman, Daniel Laheru, Manuel Hidalgo, Antonio Jimeno, Anirban Maitra, William H Matsui
Journal: Cancer Research (2008)

Abstract Pancreatic adenocarcinoma is a highly aggressive cancer that is largely resistant to current therapies and portends a median survival for patients of 9-12 months. Resistance may be due to a subpopulation of cells that are chemoresistant and able to support tumor propagation, such as cancer stem cells (CSCs). CSCs have emerged as attractive therapeutic targets, but the development of effective therapies requires the isolation of highly purified cell populations. Surface antigen expression has been used to identify CSC in most systems, however, methods based on functional properties, such as Hoechst dye exclusion or aldehyde dehydrogenase (ALDH) activity, can enhance stem cell isolation from normal and malignant tissues. We compared CSCs from pancreatic adenocarcinomas isolated by cell surface phenotype, ALDH activity, or both. Initially, we studied ALDH expression in human pancreatic cancer cell lines (CAPAN-1, DAN-G, CFPAC-1) using the Aldefluor assay. We found that each line contained a small population of ALDH+ cells (0.9-6.5% of total cells) that demonstrated increased clonogenic growth potential both in vitro and in vivo compared to ALDH- cells. Next, we compared ALDH expression with the published pancreatic CSC phenotype (CD24+CD44+) in cell lines and low-passage xenografts derived from primary human tumor specimens. Interestingly, we found that the putative CSC populations were only partially overlapping since 7-18.2% of the ALDH+ cells were CD44+CD24+ and only 4.2-36.2% of the CD44+CD24+ cells expressed ALDH. We compared CD44+CD24+ and CD44+CD24+ALDH+ cells isolated from 5 unique human pancreatic cancer xenografts and found that the CD44+CD24+ALDH+ cells were more tumorgenic in NOD/SCID mice. We also evaluated ALDH expression in primary pathologic specimen from 268 patients with pancreatic cancer by immunohistochemistry and found small, intensely positive cells with round or oval nuclei near the base of cancerous glands or at the invasive front in 90 (34%) of those patients. Furthermore, the presence of these cells was significantly associated with poorer overall survival (14 vs. 18 mos, p=0.02). We have begun to evaluate the mechanism by which pancreatic CSCs may be involved in more aggressive disease and found that CD44+CD24+ALDH+ cells isolated from tumor xenografts have significantly lower expression of E-cadherin and higher expression of Slug, a transcriptional repressor of E-cadherin, compared to ALDH+ or ALDH- cells. Therefore, ALDH appears to mark highly clonogenic pancreatic CSCs. Moreover, increased features associated with epithelial-to-mesenchymal transition may play a role in the correlation of ALDH+ cells with long-term outcomes.
Abstract 15657: Regulation of Cardiac Regeneration by Hippo Pathway and Dystrophin Glycoprotein Complex
Authors: Yuka Morikawa, James F Martin
Journal: Circulation (2014)

Regeneration of the mammalian heart is limited in adults. In rodents, endogenous regenerative capacity exists during development and in neonate but is rapidly repressed after birth. We are elucidating the mechanisms responsible for regenerative repression and applying this knowledge to reactivate cardiac regeneration in adult hearts. We have previously shown that the Hippo pathway is responsive for regenerative repression, however, the molecular and cellular mechanism responsible remain unclear. The Hippo pathway controls heart size by repressing myocardial cell proliferation during development. By deleting Salv, a modulator of Hippo pathway, we found myocardial damage in the postnatal and adult heart was repaired anatomically and functionally. This heart repair occurred primarily through proliferation of preexisting cardiomyocyte. We observed that cardiomyocytes in border the zone protrude and fill the damage area during Hippo-mediated cardiac regeneration and thus preventing formation of fibrotic scars. The molecular analysis identified components of dystrophin glycoprotein complex (DGC) as downstream targets of Hippo pathway. The DGC anchors the cytoskeleton and extracellular matrix and is involved in cell migration. The studies using the muscular dystrophy mouse model, mdx, reveals that DGC is required for endogenous cardiac regeneration and cardiomyocyte protrusion. Taken together, we show that cardiomyocyte protrusion is an essential process for cardiac regeneration and the Hippo pathway regulates it through regulating DGC. Our studies provide insights into the mechanisms leading to repair of damaged hearts from endogenous cardiomyocytes and novel information into DGC function.