tbuckley/cabot-search huggingface dataset:
Varicella zoster virus vaccination policies and surveillance strategies in Europe
Authors: A Pinot de Moira, A Nardone
Journal: Eurosurveillance (2005)

The incorporation of varicella zoster virus (ZVV) vaccination in childhood immunisation schedules is becoming an increasingly common option in Europe. The current study forms part of the European Sero-Epidemiology Network 2 (ESEN2) organisational analysis for VZV and describes current passive immunisation policies, as well as current and proposed active immunisation strategies, and existing surveillance systems for diseases caused by the varicella zoster virus in ESEN countries. A questionnaire was compiled and distributed to 23 participating countries. A VZV vaccine is currently licensed in 14 of the 20 participating ESEN countries. Germany is the only country to have incorporated VZV vaccination into its routine childhood immunisation programme. Three further countries currently recommend vaccination of children against VZV and five countries are also considering introducing routine immunisation against VZV for children. However, of the eight countries with or considering introducing childhood VZV immunisation, only six have case-based mandatory notification of varicella, and only two countries have primary care surveillance data available for herpes zoster.
Abstract 1417: Stem Cell Based Gene Transfer of GATA4 Fused with Cell Penetrating Peptide VP22 for Cardiac Repair
Authors: Jing Bian, Zoran B Popović, Farhad Forudi, Matthew Kiedrowski, Marc S Penn
Journal: Circulation (2008)

We have recently demonstrated that GATA4 fused with cell penetrating peptide VP22 is an efficacious strategy for delivering a cardiac transcription factor to the myocardium in ischemic cardiomyopathy. We have similarly demonstrated that the delivery of SDF-1 to the heart soon after myocardial infarction (MI) leads to stem cell recruitment and preservation of cardiac myocytes. We hypothesized that by combining VP22:GATA4 and SDF-1 delivery to the myocardium we could recruit stem cells to the heart and force their differentiation following MI. We used the infusion of genetically modified mesenchymal stem cells (MSC) to deliver the SDF-1 and VP22:GATA4 to the heart after MI. MSCs isolated from bone marrow and stably transduced with Lentiviral VP22:GATA4 or SDF-1 were infused through tail vein one week after LAD ligation in Lewis rat model. Experimental groups consisted of Saline, Control MSC, SDF-1 MSC, VP22:GATA4 MSC or combined VP22:GATA4 and SDF-1 MSC. In each situation 2 million MSC were infused, but no more than 1 million of any specific genetically modified MSC was infused. Ejection fraction was quantified by echocardgraphy 2 and 6 weeks after cell infusion. At 2 w after cell infusion we observed a 23 ± 1% and 40 ± 5% improvements in ejection fraction of MSC and SDF-1 groups relative to saline controls. We observed a 23 ± 4% decline in function in the VP22:GATA4 group and no improvement in the combination group. At 6 weeks after cell infusion, we observed no significant improvements in the MSC group and a 47 ± 10% and a 20 ± 4% improvements in the SDF-1 and combo groups, the function in the VP22:GATA4 group improved to have no significant difference compared to saline control. Intravenous infusion of MSC can be used to deliver natural and chimeric proteins to the myocardial tissue following MI. The initial decline in function in those animals that received VP22:GATA4 expressing MSC suggest that forced induction of cardiac differentiation soon after MI may have detrimental effects on myocardial tissue leading to increased cardiac myocyte death and adverse remodeling. These findings have implications in strategies being developed to induce myocardial regeneration soon after MI.
Abstract 16059: Racial and Ethnic Differences in Preserved Ejection Fraction and Reduced Ejection Fraction Incident Heart Failure in a Multiracial Cohort of Post-Menopausal Women
Authors: Abdullah Quddus, Liviu Klein, Jacques E Rossouw, Wen-Chih Wu, Simin Liu, Nina S Wampler, Lisa W Martin, Karen Margolis, Karen Johnson, Randi Foraker, Giselle Corbie-Smith, Khadijah Breathett, Matthew Allison, Joanne E Manson, Charles B Eaton
Journal: Circulation (2014)

Introduction: We compared the incidence of Heart Failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) in African-Americans (AA), Hispanic (H) and Caucasian (C) women in the Women Health Initiative (WHI) and evaluated risk factors to explain differences in rates of incident hospitalized HFpEF and HFrEF . METHODS: A multi-racial cohort of 42,272 post-menopausal women that oversampled for H and AA were followed for mean of 11.3 years and evaluated for incident HFpEF or HFrEF. Risk factors for incident HFpEF and HFrEF were tested using Cox proportional hazards regression models for AA, H and C with appropriate sample weighting. RESULTS: There were a total of 1497 incident cases of HF, of which, 632 were HFpEF, 545 HFrEF, and 320 with an unknown ejection fraction. Age, SES, hypertension, diabetes, tobacco use, CHD were risk factors for both HFpEF and HFrEF whereas obesity, number of co-morbid conditions, and anemia were risk factors for HFpEF only (p &lt;0.001). After adjusting for age, and compared to C, HFpEF and HFrEF were more common in AA (HR 1.12 and 1.43) and less common in H (HR 0.60 and 0.70). For HFpEF, the differences between AA and C were explained by income as the HR is no longer significant after adjusting for income (HR = 0.99; CI 0.73 - 1.33) and clinical risk factors such as hypertension, diabetes, and obesity (HR 0.74; CI 0.53 - 1.02). For HFrEF, the differences between AA and C were only partially explained by income disparities (HR 1.17, CI 0.85 - 1.60) while hypertension, diabetes, dyslipidemia and coronary heart disease played a more important role (HR 0.75; CI 0.52 - 1.07). For Hispanics, the inverse association for HFpEF and HFrEF were accentuated after accounting for income disparities (HR=0.51 and 0.47), and similarly clinical risk factors such as hypertension, diabetes, obesity and dyslipidemia (HR=0.46 and 0.45). CONCLUSION: In post-menopausal women, incident HFpEF and HFrEF are more common in AA than C, while the incidence is lower in H women. Differences in clinical risk factors and income explain the differences in AA compare to C, but not the inverse associations in H.
背痛-寒颤-呼吸困难
Authors: 吴东, 黄晓明, 王玉
Journal: BMJ (2009)

患者男性,92岁,因突发背痛伴剧烈寒颤5 h入院.5 h前午餐后患者突感背部剧痛.伴恶心.疼痛位于右侧腰背部,无放射.无腹痛、胸痛、呼吸困难.既往有冠心病史,陈旧性心肌梗死,心功能2～3级;慢性肾功能不全,长期非透析治疗;胆囊结石;胃大部切除术后。
Effect of a 2-amino group on receptor tyrosine kinase inhibition and antiangiogenic activity of 4-anilinosubstituted pyrrolo[2,3-d]pyrimidines
Authors: Ojas A. Namjoshi, Aleem Gangjee, Michael Ihnat, Miller Todd
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

243 

Several tumors have dysfunctional receptor tyrosine kinases (RTKs) that are often over expressed and promote inappropriate signaling that has implications in tumor growth and metastsis. Thus inhibition of RTKs has provided a new paradigm for cancer therapy. Many of the RTK inhibitors which are marketed or in clinical trials were designed to compete with ATP at the ATP binding site of kinases. Gangjee et al . published a series of 2-amino-4-anilino substituted pyrrolo[2,3- d ]pyrimidines as RTK inhibitors. The 2-amino group was designed to provide an additional hydrogen binding site with the hinge region of the binding pocket and to increase potency. Most of the initially published RTK inhibitors (such as 4-anilinoquinazolines, 4-anilinopyridopyrimidines) did not have such an additional binding site. In order to determine the validity of our hypothesis, a series of pyrrolo[2,3- d ]pyrimidines were synthesized without the 2-amino group and evaluated against tyrosine kinases. This report will discuss the synthesis and biological activities of this new 2-desamino series along with the previously reported analogs.
EUCAST Technical Note on tigecycline
Authors: D.F.J. Brown, R. Canton, A.P. MacGowan, J.W. Mouton, A. Rodloff, F. Goldstein, I. Odenholt, M. Steinbakk, P. Varaldo, W. Hryniewicz, G. Kahlmeter
Journal: Clinical Microbiology and Infection (2006)
Carvedilol Protects Better Against Vascular Events Than Metoprolol in Heart Failure
Authors: Willem J. Remme, Christian Torp-Pedersen, John G.F. Cleland, Philip A. Poole-Wilson, Marco Metra, Michel Komajda, Karl Swedberg, Andrea Di Lenarda, Phillip Spark, Armin Scherhag, Christine Moullet, Mary Ann Lukas
Journal: Journal of the American College of Cardiology (2007)
Abstract P101: Comparison of Ventilation Rate Measured with Thoracic Bioimpedance and with Capnography during Out-of-Hospital Cardiopulmonary Resuscitation
Authors: Ahamed H Idris, Sarah Beadle, Mohamud Daya, Dana Zive
Journal: Circulation (2008)

Objective: To determine the ability of thoracic bioimpedance to measure ventilation rate during cardiac arrest and CPR. Methods: Philips MRx devices monitored 32 patients during out-of-hospital cardiac arrest and CPR. The devices recorded chest compressions with an accelerometer, continuous 1-lead EKG, thoracic bioimpedance, and continuous capnography. Of the 32 files, 4 were not used in this study because of incomplete recording. Two reviewers manually annotated ventilation waveforms independently using Laerdal QCPR software, which also automatically annotated ventilation through the bioimpedance channel. Reviewers manually measured ventilation rate (number of breaths/min) recorded with capnography for each 1 minute epoch, which were matched and compared with those measured through bioimpedance for each patient file (N = 28). A total of 585 1-minute epochs were measured and compared. We assessed intra-class correlation for 2 individual raters for ventilation rates measured with capnography and with annotated bioimpedance to establish inter-user reliability of measurements. Ventilation rate measured with capnography vs. bioimpedance was compared with simple regression. Results: The majority (60%) of ventilation rates measured with capnography and with automated software bioimpedance were within 2 breaths/min of each other. After manual annotation of the bioimpedance channel, 81% of 1-min epochs were within 2 breaths/min of rates measured with capnography. Ventilation rate measured with capnography had good correlation with bioimpedance (r = .82, p &lt; .0001). Inter-rater agreement is estimated to be 0.96 for ventilation rate measured with capnography and 0.93 for rate measured with bioimpedance. Discussion: The software occasionally missed obvious ventilation waveforms and occasionally annotated waveforms obviously caused by chest compressions. Manual review and annotation improved the accuracy of ventilation rates measured with bioimpedance. Approximately 75% to 90% of recordings made with the Philips MRx device are expected to be useful for measurement. Conclusion: Ventilation rate measured with thoracic bioimpedance alone is acceptable using the Philips MRx device. Inter-rater agreement for measurements is excellent.
Abstract 20634: Outcomes of Medical Treatment for Aortic Stenosis in Japan
Authors: Eri Minamino, Takao Kato, Moriaki Inoko
Journal: Circulation (2014)

Introduction:  Survival curves of aortic stenosis (AS) derived from 1960’s retrospective studies show that the interval between the onset of symptoms and the time of death is approximately 2 years in patients with heart failure, 3 years in those with syncope, and 5 years in those with angina. The overall 1-year survival rate of patients with severe aortic stenosis (AS) assigned to standard therapy without transcatheter aortic valve replacement in the PARTNER trial was approximately 50%.   Hypothesis:  We hypothesized that the outcomes of patients with severe AS who were treated with medications improved compared with those of such patients in historical reports or selected candidates for randomized trials.   Methods:  We retrospectively analyzed 139 AS patients who were managed conservatively and followed up for more than 3 years in 3 institutions in Japan between 2001 and 2012. The patients were categorized into the following 3 groups based on the initial symptoms: patients with symptoms of heart failure (Group A); patients with angina pectoris or syncope (Group B); and asymptomatic patients (Group C). The patients were also segregated into 3 groups according to AS severity on echocardiography. Severe AS was defined as a peak aortic-jet velocity of >4 m/s; moderate AS, as 3-4 m/s; and mild AS, as    Results:  The overall survival rate was significantly lower in Group A (67%) than in Group B (93%) and Group C (93%) (left upper panel; p    Conclusions:  Heart failure symptoms at presentation continue to influence patient outcomes. The outcomes of patients with severe AS who were treated without surgery or catheter interventions improved compared with those of such patients in historical reports.
Abstract 3499: Ethnic and Gender Differences in Large and Small Artery Elasticity: Results of the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Daniel A Duprez, David Herrington, Darryl Prime, Pamela Ouyang, Graham R Barr, David A Bluemke
Journal: Circulation (2007)

Background: Arterial stiffness is a surrogate marker for cardiovascular morbidity and mortality; it may help account for ethnic and gender differences in cardiovascular risk. Objective: We examined the large and small artery elasticity (LAE, SAE) according to ethnicity and gender in the large MESA cohort study. Methods: A total of 3293 women and 3000 men aged 45– 84 years free of clinically recognized cardiovascular disease were recruited in 6 US communities from white, African American, Hispanic, and Chinese ethnicity. Pulse wave contour registration at the radial artery was performed in all subjects in a supine position using radial tonometry. LAE and SAE were derived from diastolic pulse contour analysis. Results: A strong gradient of arterial elasticity was seen per decade of age, about 1.2 ml/mmHgx10 for LAE and 0.7 ml/mmHgx100 for SAE. Table 1 presents mean levels of LAE and SAE, both unadjusted and simultaneously adjusted by regression for age, race/ethnicity, gender, center and education. We also adjusted for variables used in the estimation of arterial elasticity (height, heart rate, blood pressure and BMI), thus examining the information unique to the pulse wave contour. Much of the gender difference in arterial elasticity is explained by the gender difference in height. After adjustment LAE did not differ by ethnicity, but African Americans had lower levels of SAE. Conclusions: African Americans free of overt cardiovascular disease have lower SAE but not different LAE compared to white, Chines and Hispanic ethnicity. This reduced SAE may indicate earlier vascular disease in African Americans than in other groups. Table 1
Small-Molecule Inhibition of BRD4 Is a Novel Promising Approach to Therapeutically Target Leukemia Stem Cells in AML,
Authors: Harald Herrmann, Katharina Blatt, Junwei Shi, Amy R. Rappaport, Karoline V. Gleixner, Sabine Cerny-Reiterer, Barbara Peter, Eric Wang, Wolfgang R. Sperr, James E. Bradner, Scott W. Lowe, Christopher R. Vakoc, Johannes Zuber, Peter Valent
Journal: Blood (2011)
Abstract P104: Serum 25-hydroxyvitamin D Levels and Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Jeffrey R Misialek, Alvaro Alonso, Erin D Michos, Lin Y Chen, Elsayed Z Soliman, Elizabeth Selvin, Myron Gross, John H Eckfeldt, Pamela L Lutsey
Journal: Circulation (2015)

Introduction: Low levels of serum 25-hydroxyvitamin D [25(OH)D] have been associated with an increased risk of cardiovascular disease (CVD). However, few studies have examined the association of 25(OH)D with atrial fibrillation (AF).

Hypotheses: Individuals with clinically deficient serum 25(OH)D levels (<20 ng/mL) will have an increased risk for AF, and the association will be stronger among whites than blacks.

Methods: The Atherosclerosis Risk in Communities (ARIC) study is a biracial, community-based cohort in the United States. A total of 12,300 ARIC participants (77% white, 57% women, mean age 57) with available 25(OH)D levels, and who were free of AF at baseline (1990-92), were followed through 2011. Total serum 25(OH)D was measured in stored samples at baseline using LCMS and adjusted for month of blood draw to account for seasonal differences in 25(OH)D levels. Incident AF cases were identified from electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox models were used to estimate hazard ratios and 95% confidence intervals for AF associated with serum 25(OH)D levels by clinical cut-points. Interactions by age, race, and sex were tested.

Results: During a median follow-up of 20 years, there were 1,706 incident AF events. Those with deficient 25(OH)D levels ( 30 ng/mL) after adjustment for demographics (Table, model 1). Additional adjustment for cardiovascular risk factors and history of CVD attenuated the associations (Table, models 2 and 3). A significant interaction with age (p=0.01), but not with race or sex (p >0.40), was identified, with an inverse association between serum 25(OH)D in younger but not older individuals (Table).

Conclusions: After accounting for traditional cardiovascular risk factors, low serum 25(OH)D was not associated with risk of incident AF in this community-based population. However, an apparent association in younger individuals (47-57) warrants further investigation.

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Results of a Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients (Pts) with Activating FLT3 Mutations
Authors: Jasleen K. Randhawa, Hagop M. Kantarjian, Gautam Borthakur, Philip Alastair Thompson, Maria Konopleva, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Tapan M. Kadia, Zeev Estrov, Abhijit Ramachandran, Jamil Paradela, Michael Andreef, Mark Levis, Farhad Ravandi, Jorge E. Cortes
Journal: Blood (2014)
Abstract 5037: Phosphorylation of eNOS Corrects Diabetic Vascular Dysfunction and Improves Outcome to Stroke
Authors: Qian Li, Dmitriy Atochin, Satoshi Kashiwagi, John Earle, Annie Wang, William Sessa, Paul Huang
Journal: Circulation (2009)

Background: While diabetes is associated with diminished vascular NO levels, the precise mechanisms of diabetic endothelial dysfunction are not known. We hypothesized that deficient eNOS S1179 phosphorylation plays a key role in diabetic vascular abnormalities, and that increasing S1179 phosphorylation may improve endothelial function. To test this hypothesis, we created eNOS knock-in mice that carry a S1179D mutation in the eNOS gene, resulting in the generation of a phosphomimetic form of eNOS with increased enzymatic activity and NO generation. We bred these animals to db/db mice to obtain S1179D-db/db mice to test whether modulation of the S1179 phosphorylation site could overcome diabetic vascular dysfunction, and whether this could affect stroke size in vivo. Experimental Procedures: Adult male mice were anesthetized by 30 % oxygen, 70 % nitrous oxide, and 1.5 % isoflurane. Body temperature was maintained at 36–37°C. Vessel reactivity studies were performed on isolated pressurized carotid arteries. For stroke studies we used the middle cerebral artery occlusion with subsequent reperfusion by filament with Laser Doppler cortical blood flow monitoring. Mice were examined for neurologic deficits 24 hours after stroke. Infarct sizes were determined by the indirect method by 2,3,5-triphenyltetrazolium chloride staining. Statistical analysis was performed with t-test. Results: Db/db mice showed normal levels of total eNOS, while S1179 phospho-eNOS was diminished. Db/db mice are hypertensive compared with wild-type (WT) mice (116±4 vs 93±3 mm Hg, mean± SEM). The eNOS S1179D mutation normalizes the blood pressure of db/db mice (92±5 mmHg). Carotid artery vasodilation to ACh was impaired in db/db mice (EC50 43.4±6.1 nM) compared with WT mice (16.3±2.9 nM) and S1179D-db/db mice (26.6±4.2 nM). Db/db mice show a larger stroke (100±7 mm3) than do WT (65±7 mm3) and S1179D-db/db mice (80±4 mm3, P&lt;0.05). This was associated with a functional improvement in the neurologic deficit. Conclusion: Our results establish eNOS phosphorylation as an important cause of vascular dysfunction in db/db mice, and suggest eNOS phosphorylation as a novel target for the treatment and prevention of diabetic vascular disease and stroke. This research has received full or partial funding support from the American Heart Association, National Center.
Acquired isodisomy on chromosome 13 at diagnosis results in impaired overall survival in patients with FLT3-ITD mutant acute myeloid leukaemia
Authors: J C T Loke, S Akiki, J Borrow, J Ewing, S W Bokhari, D Chandra, J Arrazi, P Hazlewood, K Arthur, J Walsh, Y Membwange, F A Wandroo, A Watts, A Borg, K Brock, P Ferguson, C Craddock, M Griffiths, M Raghavan
Journal: Leukemia (2015)
bmjlearning.com: Multimedia learning
Authors: Kieran Walsh
Journal: BMJ (2004)

“Early multimedia learning looked like a car that had been cobbled together from different scrap yards with components of different sizes, colours, models, and ages. It was a mongrel beast.”1

So said Donald Clark, a leading authority in multimedia learning in Britain. He was referring to the early flood of learning websites that had loud music and equally loud colour. Videos were mixed with animation, and graphics popped up all over the screen. The designers loved it, but users were at first bemused and then distracted, and in the end they learnt little. So far at BMJ Learning, we have erred on the side of multimedia learning for a purpose—you don't need broadband to use the site. Text is still very useful—experienced readers can read at a rate of 300 words a minute, but everyone can read at their own pace. You can also search text quickly, and we can easily update it.

However, we are building more multimedia content on the site. This month we have published a module on psoriasis. About 2% of UK adults have psoriasis, and our module outlines how to diagnose and manage patients in primary care. Traditionally, colour slides are used to support text, but here the pictures are at the core of the module. We show you pictures of patients with different types of psoriasis and then test and train your skills in diagnosing and managing the condition. Further pictures enable you to test your knowledge of some complications of psoriasis such as psoriatic arthropathy and erythrodermic psoriasis. The module also gives an update on recent advances in management such as the role of vitamin D analogues and tumour necrosis factor blockers.

To find out more, look at our new module on bmjlearning.com.