tbuckley/cabot-search huggingface dataset:
Analysis of the characteristics of the flow velocity waveforms in left atrial small arteries and veins in the dog.
Authors: F Kajiya, K Tsujioka, Y Ogasawara, O Hiramatsu, Y Wada, M Goto, M Yanaka
Journal: Circulation Research (1989)

To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We intended particularly to examine the influence of atrial contraction and relaxation on velocity waveforms to obtain some insight into the nature of the mechanical force acting on the atrial intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter of about 150-500 microns were chosen for the measurements because their walls are transparent to laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of cyanoacrylate when good-quality Doppler signals were consistently observed. Additional experiments with three dogs were performed to observe the blood velocities in the atrial artery and vein during arrhythmia. The blood velocity waveform in the artery was similar to the pattern of aortic pressure during ventricular ejection (peak velocity, 18.8 +/- 7.8 cm/sec) but was characterized by a pronounced dip during atrial contraction. The temporal coincidence between the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 micrograms i.v.), the acceleration rate of the forward flow velocity increased by 176% (p less than 0.05), and reverse flow appeared during atrial contraction in five cases out of eight (p = 0.013). The blood flow velocity in atrial small veins, on the other hand, was predominant during atrial contraction (peak velocity, 15.6 +/- 5.8 cm/sec). Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (p less than 0.01). Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in veins. The phase opposition between arterial inflow into and venous outflow from the atrial myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial myocardial contraction impedes atrial inflow and promotes venous outflow from atrial capacitance vessels.
Overcoming Preexisting Humoral Immunity to AAV Using Capsid Decoys
Authors: Federico Mingozzi, Xavier M. Anguela, Giulia Pavani, Yifeng Chen, Robert J. Davidson, Daniel J. Hui, Mustafa Yazicioglu, Liron Elkouby, Christian J. Hinderer, Armida Faella, Carolann Howard, Alex Tai, Gregory M. Podsakoff, Shangzhen Zhou, Etiena Basner-Tschakarjan, John Fraser Wright, Katherine A. High
Journal: Science Translational Medicine (2013)

Capsid decoys enhance the efficacy of AAV vector transduction after systemic delivery in the presence of neutralizing antibodies.
A Common Deletion in the APOBEC3 Genes and Breast Cancer Risk
Authors: Jirong Long, Ryan J. Delahanty, Guoliang Li, Yu-Tang Gao, Wei Lu, Qiuyin Cai, Yong-Bing Xiang, Chun Li, Bu-Tian Ji, Ying Zheng, Simak Ali, Xiao-Ou Shu, Wei Zheng
Journal: JNCI Journal of the National Cancer Institute (2013)

Genome-wide association studies (GWASs) have identified multiple genetic susceptibility loci for breast cancer. However, these loci explain only a small fraction of the heritability. Very few studies have evaluated copy number variation (CNV), another important source of human genetic variation, in relation to breast cancer risk.We conducted a CNV GWAS in 2623 breast cancer patients and 1946 control subjects using data from Affymetrix SNP Array 6.0 (stage 1). We then replicated the most promising CNV using real-time quantitative polymerase chain reaction (qPCR) in an independent set of 4254 case patients and 4387 control subjects (stage 2). All subjects were recruited from population-based studies conducted among Chinese women in Shanghai.Of the 268 common CNVs (minor allele frequency ≥ 5%) investigated in stage 1, the strongest association was found for a common deletion in the APOBEC3 genes (P = 1.1×10(-4)) and was replicated in stage 2 (odds ratio =1.35, 95% confidence interval [CI] = 1.27 to 1.44; P = 9.6×10(-22)). Analyses of all samples from both stages using qPCR data produced odds ratios of 1.31 (95% CI = 1.21 to 1.42) for a one-copy deletion and 1.76 (95% CI = 1.57 to 1.97) for a two-copy deletion (P = 2.0×10(-24)).We provide convincing evidence for a novel breast cancer locus at the APOBEC3 genes. This CNV is one of the strongest common genetic risk variants identified so far for breast cancer.
Research project will use cervical cells to predict risk of cancers
Authors: I. Torjesen
Journal: BMJ (2015)

A European research project is aiming to develop new ways for testing cervical endothelial cells, collected during cervical screening tests, to predict women’s risk of breast, endometrial, and ovarian cancer as well as cervical cancer.

The FORECEE (4C) project involves 14 European research partners and has been awarded a €7.9m (£5.7m; $8.7m) grant by the European Commission and £1m by the Eve Appeal charity to enable it to use “multi-omics” to identify markers for the most aggressive types of the four cancers affecting women. Multi-omics means that the researchers use genome, epigenome (environmental factors that turn genes on and off and affect how cells …
The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Acid-Mediated Invasion
Authors: Ariosto S. Silva, Jose A. Yunes, Robert J. Gillies, Robert A. Gatenby
Journal: Cancer Research (2009)

A number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral and peritumoral acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH buffers to increase the acidic pHe of tumors in vivo and investigate the chemical specifications of an optimal buffer for such purpose. We show that increased serum concentrations of the sodium bicarbonate (NaHCO(3)) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of tumor acid concentrations significantly reduces tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing buffer effectiveness is its pK(a). This indicates that NaHCO(3), with a pK(a) of 6.1, is not an ideal intratumoral buffer and that greater intratumoral pHe changes could be obtained using a buffer with a pK(a) of approximately 7. The simulations support the hypothesis that systemic pH buffers can be used to increase the tumor pHe and inhibit tumor invasion.
Adaptive Optics Fundus Camera to Examine Localized Changes in the Photoreceptor Layer of the Fovea
Authors: Yoshiyuki Kitaguchi, Takashi Fujikado, Kenichiro Bessho, Hirokazu Sakaguchi, Fumi Gomi, Tatsuo Yamaguchi, Naoki Nakazawa, Toshifumi Mihashi, Yasuo Tano
Journal: Ophthalmology (2008)
Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders
Authors: Gurudutt Pendyala, Howard S Fox
Journal: Genome Medicine (2010)

Diagnosing neurodegenerative diseases, monitoring their progression and assessing responses to treatments will all be aided by the identification of molecular markers of different stages of pathology. Protein biomarkers for HIV-associated neurocognitive disorders that have been discovered using proteomics include complement C3, soluble superoxide dismutase and a prostaglandin synthase. Metabolomics has not yet been widely used for biomarker discovery, but early work shows that it has great potential.
Association of Aspirin and Nonaspirin Nonsteroidal Anti-inflammatory Drugs With Cancer Incidence and Mortality
Authors: A. Bardia, J. O. Ebbert, R. A. Vierkant, P. J. Limburg, K. Anderson, A. H. Wang, J. E. Olson, C. M. Vachon, J. R. Cerhan
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundThe cancer chemopreventive benefits of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are incompletely defined and may vary by smoking history. We evaluated associations between aspirin and nonaspirin NSAID use with cancer incidence and mortality stratified by smoking history in the Iowa Women's Health Study, a prospective cohort of postmenopausal women.
A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies
Authors: M. von Mehren, R.J. Schilder, J.D. Cheng, E. Temmer, T.M. Cardoso, F.G. Renshaw, E. Bayever, P. Zannikos, Z. Yuan, R.B. Cohen
Journal: Annals of Oncology (2008)
Expression of members of the phospholipase A<sub>2</sub>family of enzymes in human nasal mucosa
Authors: J. Lindbom, A.G. Ljungman, M. Lindahl, C. Tagesson
Journal: European Respiratory Journal (2001)

Phospholipase A 2 (PLA 2 ) is a family of enzymes thought to play a key role in inflammation by releasing arachidonic acid for the synthesis of eicosanoids and lysophospholipid for the synthesis of platelet-activating factor. However, the precise contribution of different PLA 2 types to the formation of inflammatory lipid mediators in the upper airways is not known and the expression of different PLA 2 genes in the human nasal mucosa has not been examined. This study therefore investigated the occurrence of messenger ribonucleic acids (mRNAs) for different PLA 2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium-independent (aiPLA 2 ), and calcium-independent membrane bound PLA 2 , (iPLA 2 -2)) in the nasal mucosa of five healthy human subjects. Using reversed transcription-polymerase chain reaction (RT-PCR) techniques it was found that all these PLA 2 types except PLA 2 V were expressed in all subjects, whereas PLA 2 V was detected in only one individual on one single occasion. The relative abundance of the different PLA 2 transcripts were aiPLA 2 &gt;X≈IVA&gt;IIA≈IIE≈IVB≈VI&gt;IB≈IID≈III≈IVC≈VII≈iPLA 2 -2. To further quantify the mRNA-expression of PLA 2 X, IVA and IIA, the samples were reanalysed with a quantitative PCR-technique utilizing competitive deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA 2 X, IVA and IIA mRNA were then estimated to 0.9±0.2, 1.1±0.7, and 0.0025±0.0021 amol (mean±se), respectively, confirming the relative abundance of these PLA 2 transcripts and indicating that the recently described PLA 2 X form is relatively strongly expressed. These findings demonstrate that a large number of PLA 2 types are expressed in the normal human nasal mucosa. Moreover, this investigation demonstrates, for the first time, the presence of the newly discovered phospholipase A 2 forms IID, IIE, III, IVB, IVC, X and calcium-independent membrane bound phospholipase A 2 in the human nasal mucosa and raises the possibility that one or several of these may be involved in inflammatory reactions in the nose.
Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey
Authors: Antoine Deschildre, Christophe Marguet, Julia Salleron, Isabelle Pin, Jean-Luc Rittié, Jocelyne Derelle, Rola Abou Taam, Mickael Fayon, Jacques Brouard, Jean Christophe Dubus, Daniel Siret, Laurence Weiss, Guillaume Pouessel, Laurent Beghin, Jocelyne Just
Journal: European Respiratory Journal (2013)

Omalizumab has been shown to reduce exacerbation rates in moderate to severe allergic asthma. Our aim was to evaluate omalizumab efficacy and safety in a real-life setting in severe asthmatic children. 104 children (aged 6–18 years), followed up in paediatric pulmonary tertiary care centres, were included at the beginning of omalizumab treatment. Asthma control levels, exacerbations, inhaled corticosteroid dose, lung function and adverse events were evaluated over 1 year. Children were characterised by allergic sensitisation to three or more allergens (66%), high IgE levels (mean 1125 kU·L −1 ), high rate of exacerbations (4.4 per year) and healthcare use during the previous year, and high inhaled corticosteroid dose (mean 703 μg equivalent fluticasone per day). Asthma control levels defined as good, partial or poor, improved from 0%, 18% and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p&lt;0.0001). Exacerbation and hospitalisation rates dropped by 72% and 88.5%, respectively. At 12 months, forced expiratory volume in 1 s improved by 4.9% (p=0.023), and inhaled corticosteroid dose decreased by 30% (p&lt;0.001). Six patients stopped omalizumab for related significant adverse events. Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials.
International approaches to the prescription of long-term oxygen therapy
Authors: M. Tor, H. Turker
Journal: European Respiratory Journal (2002)

To the Editor: 

We read with interest the article by Wijkstra et al . 1, in which the authors described the results of an international survey that was undertaken to compare how respirologists prescribed oxygen. I would like to contribute to the area of oxygen prescriptions and share the experience gained at a tertiary referral hospital in Turkey.

In Turkey, we require patients to be in a sitting position during testing and the resting arterial oxygen saturation ( S a,O2) to be 90%. We generally prefer to prescribe the resting flow during sleep, but in some instances, we …
Cerebrovascular Reactivity, Intima-Media Thickness, and Nephropathy Presence in Patients With Type 1 Diabetes
Authors: Grzegorz M. Kozera, Bogumił Wolnik, Katarzyna B. Kunicka, Sebastian Szczyrba, Joanna Wojczal, Ulf Schminke, Walenty M. Nyka, Leszek Bieniaszewski
Journal: Diabetes Care (2009)

OBJECTIVE Cerebrovascular reactivity impairment was reported as a marker of cerebral microangiopathy in long-term type 1 diabetes. Intima-media complex thickening reflects early stages of macroangiopathy in type 1 diabetes. The analysis of the relationship between these variables and other microangiopathic complications might serve as a beneficial indicator for early prophylaxis in these patients. RESEARCH DESIGN AND METHODS Vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery were measured with transcranial Doppler in 59 patients (median age 32.0 years, range 20–51, 36 females) with type 1 diabetes, without history of cerebrovascular events, and 30 healthy control subjects (median age 31.5 years, range 25–39, 15 females). The relationships between the presence of selected vascular complications of type 1 diabetes and biochemical parameters, intima-media thickness (IMT), and VMRr and BHI in patients were analyzed. RESULTS VMRr and BHI were lower in patients with type 1 diabetes when compared with healthy subjects (81.5 vs. 100%, P &amp;lt; 0.01, and 1.6 vs. 2.2, P = 0.04, respectively), whereas IMT was significantly higher in patients then in healthy control subjects (0.36 vs. 0.30 mm, P = 0.001). However, no association of IMT with VMRr was found. We found a significant reduction of VMRr and BHI in patients with diabetic nephropathy. CONCLUSIONS The presence of diabetic nephropathy, but not IMT, can be regarded as an indicator of cerebral microangiopathy severity in patients with type 1 diabetes.
A Placebo-Controlled Study of Guanfacine in the Treatment of Children With Tic Disorders and Attention Deficit Hyperactivity Disorder
Authors: L Scahill, P B Chappell, Y S Kim, R T Schultz, L Katsovich, E Shepherd, A F Arnsten, D J Cohen, J F Leckman
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). METHOD: Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. RESULTS: Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.
Response to Letters Regarding Article, “Percutaneous Treatment With Drug-Eluting Stent Implantation Versus Bypass Surgery for Unprotected Left Main Stenosis: A Single-Center Experience”
Authors: Alaide Chieffo, Nuccia Morici, John Cosgrave, Matteo Montorfano, Flavio Airoldi, Mauro Carlino, Iassen Michev, Gloria Melzi, Giuseppe Sangiorgi, Antonio Colombo, Francesco Maisano, Ottavio Alfieri, Erminio Bonizzoni
Journal: Circulation (2006)
Operations for Duodenal Ulcer Disease
Authors: Paul H. Jordan
Journal: Annual Review of Medicine (1989)

Operative treatment of duodenal ulcer has been restricted to the small proportion of ulcer patients who have complications of ulcers or to those patients who do not respond to medical treatment. The principal surgical procedures that have been used include different types of gastric drainage, gastric resection, gastric denervation, or various combinations of these principles. Initially, the primary objective of ulcer surgery was to prevent recurrent ulcer. Currently, the objectives of operation are to cure an ulcer without a recurrent ulcer or any undesirable sequelae developing as a result of altered gastric physiology. Perhaps no operation will satisfy each of these conditions for every patient. Parietal cell vagotomy without a drainage procedure, the latest contribution to ulcer surgery, has been intensively studied for 19 years. The operative mortality of 0.26%, the recurrence rate of 4 to 11%, and virtually no significant side effects have caused the operation to become the procedure of choice for an increasingly large number of gastric surgeons.
Lack of funding could undermine UK antibiotic resistance strategy, say experts
Authors: A. O'Dowd
Journal: BMJ (2013)

Biology experts have raised several concerns about the government’s plans for how to deal with growing antimicrobial resistance.

Funding, prioritisation, surveillance, and early warning response plans, along with leadership, were all areas of concern raised during an evidence session held on 18 December of the House of Commons Science and Technology Committee’s inquiry into antimicrobial resistance.

MPs asked the witnesses whether they thought that the government’s antimicrobial resistance strategy,1 published in September, would be successful in slowing down growing resistance to antibiotics.

The strategy includes plans for better education and training in prescribing of antibiotics to reduce inappropriate use and treatment, better monitoring of bacteria, and more …
Turner's Phenotype: Pregnancy and Cyanotic Congenital Heart Disease
Authors: A. Pidd Miller
Journal: JAMA (1970)

<h3>To the Editor.—</h3> This case is reported because of the typical findings to Turner's syndrome in a young pregnant woman with cyanotic congenital heart disease. This patient, a 24-year-old housewife, was the sixth child of a 40-year-old mother with an uncomplicated pregnancy. All siblings are apparently normal. Her birth weight was 8 Ib, and there was no history of peripheral edema during infancy. During infancy cyanotic congenital heart disease was diagnosed which caused slight restriction of her activities during the preschool years. At the age of 6 years she was seen by a pediatric cardiologist who advised that surgical correction of the heart defect was not possible; he did not give a specific diagnosis. She had the usual childhood diseases hut was never seriously ill or admitted to the hospital and had never received any type of heart medication. Menarchy occurred at the age of 14 years. As an adult
A systematic review of randomised controlled trials of interventions reporting outcomes for relatives of people with psychosis
Authors: Fiona Lobban, Adam Postlethwaite, David Glentworth, Vanessa Pinfold, Laura Wainwright, Graham Dunn, Anna Clancy, Gillian Haddock
Journal: Clinical Psychology Review (2013)

Relatives play a key role in supporting people with psychosis at all stages of recovery, but this can be associated with high levels of distress. Family interventions, with an international evidence base, improve outcomes for service users but little is known about their impact on relatives' outcomes. This review of published evaluations aimed to assess whether family interventions are effective in improving outcomes for relatives of people with psychosis, to identify the key components of effective intervention packages, and to identify methodological limitations to be addressed in future research. Fifty studies were identified which evaluated an intervention to support relatives against a control group, and in which outcomes for the relatives were reported. Thirty (60%) studies showed a statistically significant positive impact of the intervention on at least one relatives' outcome category. Eleven key intervention components were identified across all 50 studies, but there was no evidence that the presence or absence of any of these key components reliably distinguished effective from ineffective interventions. Methodological quality of studies was generally poor with only 11 studies rated as adequate using the Clinical Trial Assessment Measure (CTAM). Recommendations to improve future research include larger samples; better defined interventions and controls; true randomisation and blind assessors; clearly specified primary outcomes; pre-published analysis plans that account appropriately for missing data and clustering of data; a consensus on the most relevant outcomes to assess and valid and reliable measures to do so. Alternative research designs need to be considered to evaluate more recent approaches which focus on family support, personalised to meet individual need, and offered as an integral part of complex clinical services.