tbuckley/cabot-search huggingface dataset:
Abstract 3108: Clinical Characteristics of Left Ventricular Systolic Dysfunction without Heart Failure in Community-Based Elderly Individuals: The Cardiovascular Health Study
Authors: Jay Pandhi, Willem J Kop, John S Gottdiener
Journal: Circulation (2008)

Left ventricular systolic dysfunction without heart failure (HF), also known as asymptomatic left ventricular systolic dysfunction (ALVSD), is at least as prevalent in the general population as left ventricular systolic dysfunction with heart failure (HF-LVSD). However, the clinical characteristics of ALVSD have not been well defined in an elderly population. Our aim is to evaluate the clinical features of elderly community-based individuals with ALVSD. The Cardiovascular Health Study is a multicenter cohort study designed to assess cardiovascular risk factors and outcomes in a population 65 years and older. This study quantifies baseline demographic variables and cardiovascular risk factors in participants with ALVSD. Comparisons were made with two reference groups: individuals with HF-LVSD, and those with normal left ventricular systolic function without HF (NL-LVSF). ALVSD was present in 385 of 5152 participants (7.5%) at baseline, whereas HF-LVSD was present in 84 participants (1.6%). Among those with ALVSD, 251 (65.2%) had borderline ejection fraction (EF) (45–54%), and 134 (34.8%) had impaired EF (&lt; 45%). ALVSD was associated with elevated cardiovascular risk factors and comorbidities compared to NL-LVSF but lower than those in individuals with HF-LVSD (see table ). Among participants with ALVSD, impaired EF was associated with male sex and higher prevalence of coronary disease and LVH compared with borderline LV function. ALVSD is more common than HF-LVSD in community-dwelling elderly individuals. Furthermore, it is characterized by more cardiac risk factors and comorbidities than those with NL-LVSF, but less than those with HF-LVSD. The severity of systolic dysfunction is associated with comorbid cardiovascular risk factors. ALVSD may identify an important group of individuals at high risk for heart failure and cardiovascular mortality. Comparison of Clinical Characteristics Between ALVSD, NL-LVSF, and HF-LVSD
Abstract 20128: Effect of Renin-angiotensin Blockers on Left Ventricular Remodelling in Severe Aortic Stenosis
Authors: Serene S Goh, Poay Sian S Lee, Edgar L Tay, William K Kong, Tiong Cheng Yeo, Kian Keong Poh
Journal: Circulation (2014)

Background: The use of renin-angiotensin blockers (RAB: angiotensin converting enzyme inhibitors, ACEI and angiotensin receptor blockers, ARB) in severe aortic valve stenosis (AS) remains controversial. We aim to explore the relation on their use with degree of left ventricular (LV) remodelling in patients with normal flow (NF) and low-flow (LF) severe AS despite preserved LV ejection fraction (LVEF). Methods: We studied 423 consecutive patients with aortic valve area (AVA) 50%. Subjects with concomitant valvular pathologies, congenital heart disease or prosthetic valves were excluded. NF was categorized as LV stroke volume index (SVi) &gt; 35ml/m2. Increased left ventricular mass index (LVMI) was ≥96g/m2 and 116g/m2 in females and males respectively while abnormal relative wall thickness (RWT) was ≥0.45. Results: The median age was 74 yrs (IQR: 65-82). Prevalence of male subjects 52%, diabetes mellitus 61%, dyslipidemia 48% and hypertension 43%. A quarter of the patients were on RAB, with a mean duration of 6.7 months(IQR:1.0-72.3). Median LVMI for patients on RAB was 94.5 g/m2 (IQR: 87.3-144), whilst those without was 120.3 g/m2 (IQR: 102-159) (p=0.005). RAB use in patients with LF AS was significantly associated with normal LVMI, adjusted for hypertension (OR 2.00, p=0.002). The use of RAB had a duration dependent association with normal LVMI. Patients on RAB for a year were twice more likely to have normal LVMI (OR 2.24, p=0.048). This effect is greater in patients with 2 years of therapy (OR 3.417, p=0.002). In contrast, the use of RAB was not associated with normal LVMI in the NF group (p=0.428). There was no significant difference between use of either ACEI or ARB on LVMI (p=0.855). Patients on RAB had less risk of having concentric hypertrophy (OR= 0.373, p=0.009) and eccentric hypertrophy (0.392, p=0.025) as compared to those without. Conclusion: Use of RAB in LF severe AS may be associated with beneficial remodeling of the LV especially if prescribed for more than a year. Further studies are warranted to determine the deferential effects of RAB on clinical outcomes in LF versus NF AS.
Debate on Viagra must extend to rationing Inspecting private hospitals BMA wants a London health strategy Most flexible trainees are women
Authors: Linda Beecham
Journal: BMJ (1999)

# Debate on Viagra must extend to rationing {#article-title-2}

The BMA has repeated its plea that the current debate on sildenafil (Viagra) should be broadened into one on rationing.

At last week's council meeting the chairman of the General Practitioners Committee, Dr John Chisholm, said that the health secretary was right to make a decision on rationing Viagra but wrong to let his decision be determined by his wish to keep expenditure on treatment for impotence at the same level. It was wrong to try to distinguish between patients on the basis of the aetiology of their disease, and it was also inappropriate for urologists to assess “distress.” GPs were in a far better position to assess the distress of their patients.

The health secretary, Mr Frank Dobson, has extended the consultation period for his proposals on Viagra until 25 March, and the General Practitioners Committee has reaffirmed its advice that GPs should comply with their terms of service and prescribe Viagra on an FP10 where clinically appropriate. The chairman of council, Dr Ian Bogle, told …
Vascular endothelial growth factor mediates intracrine survival of breast cancer cells through vascular endothelial growth factor receptor-1*Authors contributed equally
Authors: Cimona Hinton, Seyha Seng, Tae-Hee Lee, Yigong Fu, Hava Avraham, Shalom Avraham
Journal: Cancer Research (2007)

2523  Vascular endothelial growth factor (VEGF) expression in breast tumors has been correlated with a poor outcome in the pathogenesis of breast cancer. Moreover, the expression, localization and function of VEGF receptors (VEGFR), VEGFR-1 and VEGFR-2 as well as neurophilin-1 (NP-1), in breast cancer are controversial. Therefore, we investigated the expression and function of VEGF, VEGFR-1 and VEGFR-2 in breast cancer cells. We observed that VEGFR-1 expression was abundant, VEGFR-2 expression was low and NP-1 expression was variable. MDA-MB-231 and MCF-7 breast cancer cells, transfected with antisense VEGF cDNA or with small-interfering RNA (siRNA) for VEGF (siVEGF), resulted in a significant reduction in VEGF expression and increased apoptosis as compared to the control cells. Additionally, specific targeted knockdown of VEGFR-1 expression by siVEGFR-1 significantly decreased the survival of breast cancer cells through down-regulation of AKT phosphorylation, while targeted knockdown of VEGFR-2 or neuropilin-1 (NP-1) expression had no effect on the survival of these cancer cells. Since a VEGFR-1 specific ligand, the placenta growth factor (PIGF), surprisingly, did not inhibit the breast cancer cell apoptosis induced by siVEGF, and since VEGFR-1 antibody also had no effects on the survival of these cells, we examined VEGFR-1 localization. VEGFR-1 was found to be predominantly expressed internally in MDA-MB-231 and MCF-7 breast cancer cells. Specifically, VEGFR-1 was found to be colocalized with Lamin A/C and was expressed mainly in the nuclear envelope in breast cancer cell lines and primary breast cancer tumors. Breast cancer cells treated with siVEGFR-1 showed significant decrease of VEGFR-1 expression and lack of VEGFR-1 expression in the nuclear envelope. These results provide evidence of a unique survival system in breast cancer cells by which VEGF can act as an internal autocrine (intracrine) survival factor through its binding to VEGFR-1, and may provide a more optimal strategy for tumor therapy based on the inhibition of angiogenesis.
512. Electroporation-Mediated Gene Transfer of Human Hepatocyte Growth Factor Reduces Bleomycin-Induced Pulmonary Fibrosis in Rats
Authors: Amiq Gazdhar, Patrick Fachinger, Jaroslaw Pierog, Steven Hyde, Mathias Gugger, Ralph Schmid, Thomas Geiser
Journal: Molecular Therapy (2004)

Background: Pulmonary fibrosis may result in respiratory failure and a poor prognosis in patients with various types of interstitial lung disorders. Hepatocyte growth factor (HGF) is a potent mitogen for alveolar epithelial cells with antiapoptotic and fibrinolytic functions, resulting in improved alveolar repair in vitro. We hypothesized that HGF may improve pulmonary fibrosis in vitro by longterm expression of HGF using electroporation-mediated, non-viral gene transfer in the bleomycin-induced lung fibrosis model.
Old Drugs for a New Bug
Authors: Brian Vastag
Journal: JAMA (2003)

IN THE SPAN OF A SEASON, A GLOBAL cadre of researchers has leveraged years of drug development into a slew of possible treatments for severe acute respiratory syndrome (SARS). Since the beginning of the SARS outbreak last spring, large drug companies have dusted off libraries of failed antivirals, famous researchers have adapted the latest anti-HIV strategy, and federal agencies have busied themselves screening thousands of existing drugs. While the World Health Organization (WHO) stopped tracking SARS cases earlier this summer, the agency warns that the disease may simply be napping. Federal agencies, led by the National Institute of Allergy and Infectious Diseases (NIAID), agree and are backing work on anti-SARS drugs.
A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation
Authors: A. Carrie, L. Jun, T. Bienvenu, M.C. Vinet, N. McDonell, P. Couvert, R. Zemni, A. Cardona, G.J.C.M. van Buggenhout, S.G. Frints, B.C.J. Hamel, C. Moraine, H.H. Ropers, T.M. Strom, G.R. Howell, A. Whittaker, M. Ross, A. Kahn, J.P. Fryns, C. Beldjord, P. Marynen, J. Chelly
Journal: Nature Genetics (1999)
Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure.
Authors: Y Ishida, J S Meisner, K Tsujioka, J I Gallo, C Yoran, R W Frater, E L Yellin
Journal: Circulation (1986)

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.
Filaggrin polymorphism P478S, IgE level, and atopic phenotypes
Authors: I.J. Wang, T.J. Lin, C.F. Kuo, S.L. Lin, Y.L. Lee, P.C. Chen
Journal: British Journal of Dermatology (2011)

Background Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. Objectives To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. Methods In total, 116 children aged 2–5 years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. Results A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88–11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37–16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01–10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93–16·60) in children with IgE level ≥ 100 kU L−1. However, the association was not evident when IgE level was < 100 kU L−1. Conclusions Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.
Authors of report on cost of visitors and migrants to the NHS reply to letter calling for end to political rhetoric on health tourism
Authors: I. Bennett, D. Waite, A. Jolly
Journal: BMJ (2015)

As authors of the Department of Health commissioned report on the cost of visitors and short term migrants to the NHS in England,1 we offer a counter interpretation to that of Schulkind and colleagues.2 Far from being “absurd,” it was a credible attempt to quantify use of NHS services by overseas visitors in the absence of any statistics directly measuring this. Peer review of our …
102. Catheter-Based Intrahepatic rAAV Gene Delivery: Influence of Infusion Flow Rate and Volume on Uptake
Authors: Lin He, Dea Nagy, Joe Vargas, Tongyao Liu, Ciaran Scallan, Shangzhen Zhou, Sharmila Vijay, Jurg Sommer, Kirk W. Johnson, Linda B. Couto, Pierce F. Glenn, Bin Yang
Journal: Molecular Therapy (2004)

Catheter-based, fluoroscopy-aided interventional radiology approaches have been utilized in a variety of clinical applications. Safe, consistent and efficient methods for liver directed gene delivery need to be developed. In this study, we examined the effects of infusion flow rate and infusion volume on intrahepatic catheter-based delivery of recombinant adeno-assocated virus 2 vectors (rAAV2) in dogs. To study the efficiency of intrahepatic gene transfer, vector (rAAV-lac Z (nonfunctional promoter)) was delivered through the hepatic artery with an occlusion balloon catheter with a protocol mimicking the clinical angiography procedure of an ongoing clinical gene transfer study in hemophilia B subjects. Three groups of beagle dogs (n=5/group) utilizing three different intrahepatic injection parameters were utilized: A) 8 ml injected at 0.1 ml/min/kg (most similar to ongoing clinical trial), B) 8 ml injected at 8 ml/min/kg and C) 40 ml injected at 8 ml/min/kg. Reproducibility and extent of gene transfer was studied by determining vector distribution and vector copy number in the liver, including individual lobes, 4 weeks post injection. Quantitative PCR using linearized standards was employed to examine vector levels in the liver. Liver histology, serum chemistries and hematology parameters were also examined in all animals over the course of 4 weeks to determine the safety of the various delivery parameters. The results indicate that intrahepatic transgene delivery was influenced by the infusion rate. On average, the rAAV2 copy number per hepatocyte with fast infusion was twice that of slow infusion (e.g. 2.8 copy/cell group B vs 1.4 copy/cell group A). Likewise, vector copy numbers per liver were approximately two times higher in the fast infusion groups (p=0.04, one-way ANOVA). Groups B (higher rate) and C (higher rate and higher volume) did not significantly differ. AAV2 vector tended to be more evenly distributed in individual livers in the fast infusion groups. No changes in chemistries nor hematology values were detected in any dogs over the course of study. Histological analysis of the liver for capsid immunoflourescence is ongoing. This study demonstrates that the infusion flow rate, in particular, can be an important variable in efficient and safe hepatic delivery of AAV.
Tiotropium for uncontrolled asthma (a meta-analysis)
Authors: Manuel Jorge, Ralph Elvi Villalobos, Marc Gregory Yu, Charles Vincent Uy
Journal: European Respiratory Journal (2013)

PURPOSE: The study aims to evaluate the efficacy of tiotropium as an add-on therapy on top of standard controller regimens for the treatment of uncontrolled asthma. Specifically, it aims to evaluate improvement in FEV1 and morning and evening PEF, reduction in exacerbations and use of controller medications, and improvement in quality of life.

METHODS: Randomized controlled trials evaluating the efficacy of tiotropium as an add-on therapy for uncontrolled asthma were included in the analysis. A systematic search was performed across electronic databases. Analysis was done using RevMan 5.1 software. Results were presented as mean differences, standard errors, and 95% confidence intervals, and were graphically presented as forest plots.

RESULTS: Of the 19 studies retrieved, five were included in the review and totaled 1643 participants. Participants in the tiotropium group had a statistically significant difference in FEV1 improvement (95% CI, 0.14 [0.09, 0.19], p<0.00001), morning PEF improvement (95% CI, 20.03 [11.71, 28.35], p<0.00001), and evening PEF improvement (95% CI, 23.13 [15.18, 31.09], p<0.00001). Among clinical outcomes, there was a trend towards benefit in the reduction of rescue medication use and improvement in quality of life. However, these effects were not statistically significant, (95% CI, 0.12 [-0.17, 0.4], p= 0.42) and (95% CI, 0.1 [-0.05, 0.25], p=0.20) respectively. Homogeneity (I2=0%, Chi2=0.47-3.22) was consistently found across all studies in each of the outcome measures.

CONCLUSIONS: Tiotropium, a long-acting anticholinergic, is associated with a statistically significant improvement in pulmonary function in terms of FEV1 and both morning and evening PEF among patients with uncontrolled asthma.
Analytic epidemiology and periodontal diseases
Authors: Brenda Heaton, Thomas Dietrich
Journal: Periodontology 2000 (2011)

Abstract The validity of epidemiological and clinical observations is paramount, not only for scientific advancement but also in evidence‐based practice. Concern regarding validity with respect to the design and conduct of analytic epidemiological studies is often under‐appreciated, partly as a consequence of our focus on randomized experimental designs as the highest standard of ‘proof’ in clinical science. We review the design, conduct and interpretation of rigorous analytic epidemiological study designs, with specific reference to periodontology. We give special emphasis to intrinsic validity and the use of focused aims to re‐frame the perspective on the strength of evidence in reviews of the literature. Specifically, we draw on the periodontal research literature to provide an overview of the appropriate design and conduct of cohort studies, including randomized designs, case–control and cross‐sectional studies. The concepts of selection bias, information bias and confounding are explored for each study design, both in general terms and with respect to a critical review of the literature on the epidemiology of periodontal diseases.
Sunscreen use: controversies, challenges and regulatory aspects
Authors: M. Lodén, H. Beitner, H. Gonzalez, D.W. Edström, U. Åkerström, J. Austad, I. Buraczewska-Norin, M. Matsson, H.C. Wulf
Journal: British Journal of Dermatology (2011)

Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight.
Rare FLT3 deletion mutants may provide additional treatment options to patients with AML: an approach to individualized medicine
Authors: N Chatain, R C Perera, G Rossetti, J Rossa, P Carloni, M Schemionek, T Haferlach, T H Brümmendorf, S Schnittger, S Koschmieder
Journal: Leukemia (2015)
A CASE OF HYPERPARATHYROIDISM WITH UNUSUAL DEFORMITY OF THE THORACIC CAGE
Authors: H O SCHNEIDER
Journal: Annals of Internal Medicine (1953)

Excerpt Hyperparathyroidism is now a well established and adequately described condition, but some of its more unusual manifestations are not so well recognized. A recently observed case presented a profound deformity of the thoracic cage, marked clubbing of the fingers, a large mass in the thyroid area which proved to be a cystic parathyroid adenoma, and an extraordinarily high serum calcium (29.0 mg. per cent). These features seemed uncommon enough to warrant reporting the case. The smooth postoperative course of the patient in the face of the exceedingly high serum calcium and large parathyroid tumor is also of interest. CASE REPORT
Leisure-time physical activity predicts complaints of snoring in women: A prospective cohort study over 10 years
Authors: Søren Spörndly-Nees, Pernilla Åsenlöf, Jenny Theorell-Haglöw, Malin Svensson, Eva Lindberg
Journal: European Respiratory Journal (2014)

Background: The impact of physical activity on sleep-disordered breathing frequency is unknown.  Objective: To assess the impact of physical activity on snoring incidence and remission in women.  Methods: A population-based sample of 4,851 women aged > 20 years responded to questionnaires in year 2000 and 2010. Based on the responses, the women were categorised into low, medium or high level of physical activity at baseline and at the follow-up.  Results: The prevalence of self-reported habitual snoring increased from 7.6% at baseline to 9.2% in 2010 (p   Conclusions: A low level of physical activity is a risk factor for future habitual snoring in women, independent of weight, weight gain, alcohol dependence and smoking. Increased physical activity can modify the risk.