tbuckley/cabot-search huggingface dataset:
Shared Treatment Decision Making: What Does It Mean to Physicians?
Authors: Cathy A. Charles, Tim Whelan, Amiram Gafni, Andy Willan, Sylvia Farrell
Journal: Journal of Clinical Oncology (2003)

Purpose: Physicians are urged to practice shared treatment decision making (STDM), yet this concept is poorly understood. We developed a conceptual framework describing essential characteristics of a shared approach. This study assessed the degree of congruence in the meanings of STDM as described in the framework and as perceived by practicing physicians. Methods: A cross-sectional survey questionnaire was mailed to eligible Ontario medical and radiation oncologists and surgeons treating women with early-stage breast cancer. Open-ended and structured questions elicited physicians’ perceptions of shared decision making. Results: Most study physicians spontaneously described STDM using characteristics identified in the framework as essential to this concept. When presented with clinical examples in which the decision-making roles of physicians and patients were systematically varied, study physicians overwhelmingly identified example 4 as illustrating a shared approach. This example was deliberately constructed to depict STDM as defined in the framework. In addition, more than 85.0% of physicians identified as important to STDM specific patient and physician roles derived from the framework. These included the following: the physician gives information to the patient on treatment benefits and risks; the patient gives information to the physician about her values; the patient and physician discuss treatment options; both agree on the treatment to implement. Conclusion: Substantial congruence was found between the meaning of STDM as described in the framework and as perceived by study physicians. This supports use of the framework as a conceptual tool to guide research, compare different treatment decision-making approaches, clarify the meaning of STDM, and enhance its translation into practice.
Fibroblast Growth Factor Receptor Signaling Dramatically Accelerates Tumorigenesis and Enhances Oncoprotein Translation in the Mouse Mammary Tumor Virus–Wnt-1 Mouse Model of Breast Cancer
Authors: Adam C. Pond, Jason I. Herschkowitz, Kathryn L. Schwertfeger, Bryan Welm, Yiqun Zhang, Brian York, Robert D. Cardiff, Susan Hilsenbeck, Charles M. Perou, Chad J. Creighton, Richard E. Lloyd, Jeffrey M. Rosen
Journal: Cancer Research (2010)

Fibroblast growth factor (FGF) cooperates with the Wnt/beta-catenin pathway to promote mammary tumorigenesis. To investigate the mechanisms involved in FGF/Wnt cooperation, we genetically engineered a model of inducible FGF receptor (iFGFR) signaling in the context of the well-established mouse mammary tumor virus-Wnt-1 transgenic mouse. In the bigenic mice, iFGFR1 activation dramatically enhanced mammary tumorigenesis. Expression microarray analysis did not show transcriptional enhancement of Wnt/beta-catenin target genes but instead showed a translational gene signature that also correlated with elevated FGFR1 and FGFR2 in human breast cancer data sets. Additionally, iFGFR1 activation enhanced recruitment of RNA to polysomes, resulting in a marked increase in protein expression of several different Wnt/beta-catenin target genes. FGF pathway activation stimulated extracellular signal-regulated kinase and the phosphorylation of key translation regulators both in vivo in the mouse model and in vitro in a human breast cancer cell line. Our results suggest that cooperation of the FGF and Wnt pathways in mammary tumorigenesis is based on the activation of protein translational pathways that result in, but are not limited to, increased expression of Wnt/beta-catenin target genes (at the level of protein translation). Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling.
BASEM moving from strength to strength: More education, more member benefits
Authors: Eleanor J Tillett
Journal: British Journal of Sports Medicine (2014)

Welcome to BASEM's highlight issue for 2014. Our mini theme edition focuses on rowing, as well as highlighting updates in clinical decision-making across the spectrum of sport and exercise medicine.

BASEM continues to build on its new foundation and we are now on a solid financial footing. Thanks to this we have been able to increase our sponsorship of educational and research opportunities and invest in the expansion of our learning programmes. Have a look at our website to review the range of travelling fellowships and research bursaries available (http://www.basem.co.uk/benefits-of-membership.shtml). With our new website imminent, this will also allow us to delve into the field of online education, which will be available at discounted rates to BASEM members. As you will see from Babette Pluim's editorial ( see page 1522 ), BJSM is already demonstrating the value of learning in this way.

The …
MRI of Tumor-Associated Macrophages with Clinically Applicable Iron Oxide Nanoparticles
Authors: Heike E. Daldrup-Link, Daniel Golovko, Brian Ruffell, David G. DeNardo, Rosalinda Castaneda, Celina Ansari, Jianghong Rao, Grigory A. Tikhomirov, Michael F. Wendland, Claire Corot, Lisa M. Coussens
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The presence of tumor-associated macrophages (TAM) in breast cancer correlates strongly with poor outcome. The purpose of this study was to develop a clinically applicable, noninvasive diagnostic assay for selective targeting and visualization of TAMs in breast cancer, based on magnetic resonanceI and clinically applicable iron oxide nanoparticles. Experimental Design: F4/80-negative mammary carcinoma cells and F4/80-positive TAMs were incubated with iron oxide nanoparticles and were compared with respect to magnetic resonance signal changes and iron uptake. MMTV-PyMT transgenic mice harboring mammary carcinomas underwent nanoparticle-enhanced magnetic resonance imaging (MRI) up to 1 hour and 24 hours after injection. The tumor enhancement on MRIs was correlated with the presence and location of TAMs and nanoparticles by confocal microscopy. Results: In vitro studies revealed that iron oxide nanoparticles are preferentially phagocytosed by TAMs but not by malignant tumor cells. In vivo, all tumors showed an initial contrast agent perfusion on immediate postcontrast MRIs with gradual transendothelial leakage into the tumor interstitium. Twenty-four hours after injection, all tumors showed a persistent signal decline on MRIs. TAM depletion via αCSF1 monoclonal antibodies led to significant inhibition of tumor nanoparticle enhancement. Detection of iron using 3,3′-diaminobenzidine-enhanced Prussian Blue staining, combined with immunodetection of CD68, localized iron oxide nanoparticles to TAMs, showing that the signal effects on delayed MRIs were largely due to TAM-mediated uptake of contrast agent. Conclusion: These data indicate that tumor enhancement with clinically applicable iron oxide nanoparticles may serve as a new biomarker for long-term prognosis, related treatment decisions, and the evaluation of new immune-targeted therapies. Clin Cancer Res; 17(17); 5695–704. ©2011 AACR.
Contractile Activity of Arterioles in the Bat Wing during Intraluminal Pressure Changes
Authors: MARY P. WIEDEMAN
Journal: Circulation Research (1966)

Spontaneous contractile activity in the smooth muscle cells that invest arteriolar vessels is widely variable. Arteriolar branches originating from the same parent vessel contract independently of one another with no similarity in frequency or duration of individual contractions. Direct microscopic observations were made of these vessels in the wing of unanesthetized bats before and after surgical denervation or nerve block by procaine. A major artery of the wing was cannulated and buffered saline was perfused in retrograde fashion to produce periods of increased intra-arterial pressure. Elevation of intraluminal pressure led to enhanced contractile activity both before and after denervation of the vessels. It is concluded that these vessels respond by contraction to increased pressure and that the response is not dependent on nervous activity.
Meta-analysis of minimally invasive internal thoracic artery bypass versus percutaneous revascularisation for isolated lesions of the left anterior descending artery
Authors: Omer Aziz, Christopher Rao, Sukhmeet Singh Panesar, Catherine Jones, Stephen Morris, Ara Darzi, Thanos Athanasiou
Journal: BMJ (2007)

<b>Objective</b> To compare outcomes between minimally invasive left internal thoracic artery bypass and percutaneous coronary artery stenting as primary interventions for isolated lesions of the left anterior descending artery. <b>Design</b> Meta-analysis of randomised and non-randomised comparative peer reviewed publications. <b>Data sources</b> Embase, Medline, Cochrane, Google Scholar, and Health Technology Assessment databases (1966-2005). <b>Review methods</b> Studies comparing the two procedures as the primary intervention for isolated left anterior descending artery stenosis were identified and the following extracted: study design, population characteristics, severity of coronary artery disease, cardiovascular risk factors, and outcomes of interest. <b>Results</b> 12 studies (1952 patients) reporting results from eight groups were included: one was a retrospective design, one prospective non-randomised, and six prospective randomised. Meta-analysis of randomised trials showed a higher rate of recurrence of angina (odds ratio 2.62, 95% confidence interval 1.32 to 5.21), incidence of major adverse coronary and cerebral events (2.86, 1.62 to 5.08), and need for repeat revascularisation (4.63, 2.52 to 8.51) with percutaneous stenting. No significant difference was found in myocardial infarction, stroke, or mortality at maximum follow-up between interventions. <b>Conclusions</b> Minimally invasive left internal thoracic artery bypass for isolated lesions of the left anterior descending artery resulted in fewer complications in the mid-term compared with percutaneous transluminal coronary artery stenting.
Stable Isotope Ratios as Biomarkers of Diet for Health Research
Authors: Diane M. O'Brien
Journal: Annual Review of Nutrition (2015)

Diet is a leading modifiable risk factor for chronic disease, but it remains difficult to measure accurately due to the error and bias inherent in self-reported methods of diet assessment. Consequently, there is a pressing need for more objective biomarkers of diet for use in health research. The stable isotope ratios of light elements are a promising set of candidate biomarkers because they vary naturally and reproducibly among foods, and those variations are captured in molecules and tissues with high fidelity. Recent studies have identified valid isotopic measures of short- and long-term sugar intake, meat intake, and fish intake in specific populations. These studies provide a strong foundation for validating stable isotopic biomarkers in the general US population. Approaches to improve specificity for specific foods are needed; for example, by modeling intake using multiple stable isotope ratios or by isolating and measuring specific molecules linked to foods of interest.
Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery
Authors: M. D. FLAMM, EDWARD B. STINSON, HERBERT N. HULTGREN, NORMAN E. SHUMWAY, E. W. HANCOCK
Journal: Circulation (1968)

Two cases of anomalous origin of the left coronary artery from the pulmonary artery are reported in asymptomatic patients 15 and 27 years of age, bringing to 30 the total number of cases of this anomaly reported in the postinfantile age group. ECG exercise tests demonstrated marked ischemic changes in both patients, but angina or abnormal shortness of breath did not develop in either patient during or after exercise. The anomalous vessel was interrupted by closure of its ostium through a pulmonary arteriotomy during cardiopulmonary bypass, a procedure felt to offer a distinct technical advantage in the surgical treatment of this condition. Following ligation of the anomalous vessel, ECG exercise tests no longer showed definitive evidence of myocardial ischemia. This is interpreted as evidence that ligation should reduce the incidence of exercise-induced sudden deaths in this anomaly.
Inside Saatchi &amp; Saatchi
Authors: Trevor Jackson
Journal: BMJ (2005)

BBC 2, 15 February, 9 50 to 10 30 pm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> How do you get people to become drinkers of a new alcoholic beverage? Given the current popular image of young Britons as alcohol fuelled party animals, you might wonder if they need much encouragement. But the manufacturers of the Brazilian drink Sagatiba want their new tipple to have a chic global presence, a must-imbibe for all the bright young things of the coolest bars in London, Amsterdam, Rome, and Paris. And they have £20m to spend on their European campaign to persuade more and more people to drink more and more of the stuff. Sagatiba the company wants Sagatiba … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Platelet Reactivity Characterized Prospectively
Authors: Samer S. Kabbani, Matthew W. Watkins, Taka Ashikaga, Edward F. Terrien, Peter A. Holoch, Burton E. Sobel, David J. Schneider
Journal: Circulation (2001)

Background — Platelet activation is pivotal in the pathogenesis of complications after percutaneous coronary interventions (PCI). We previously reported substantial interindividual variability in activation of glycoprotein (GP) IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa activation prospectively to determine whether this could differentiate patients at low risk from those at high risk for complications early and late after PCI. Methods and Results — A total of 112 patients undergoing PCI were studied. Platelet reactivity was determined with the use of flow cytometry. Patients were classified into high and low platelet reactivity groups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 μmol/L ADP. The median value was used for differentiation. The incidence during 90-day follow-up interval of a composite end point (myocardial infarction, urgent revascularization, or repeat revascularization) was determined in each group. Follow up was completed in all 112 patients. The 2 groups were similar with respect to diverse clinical characteristics. Nevertheless, the incidence of the composite end point occurred in 26.8% of the high and 7.1% in the low platelet reactivity group ( P =0.01). The difference in the composite end point was most striking during the 30- to 90-day interval after PCI (16.7% versus 1.9%; P =0.02). Repeat revascularization was more frequent in those with increased platelet reactivity (17.9% versus with 3.6%, P =0.029). Conclusions — Prospective assessment of platelet GP IIb/IIIa activation permits stratification of patients into low- and high-risk groups with respect to adverse events after PCI.
The association between blood pressure, age, and dietary sodium and potassium: a population study.
Authors: K T Khaw, E Barrett-Connor
Journal: Circulation (1988)

We examined the relationship between blood pressure and dietary sodium and potassium intake estimated from 24 hr diet recall in a population of 584 men and 718 women 30 to 79 years old in Southern California. In men, but not women, age-adjusted systolic and diastolic blood pressure correlated significantly with dietary sodium intake. In both men and women, age-adjusted diastolic blood pressure significantly inversely correlated with dietary potassium intake. Age-adjusted systolic and diastolic blood pressure correlated significantly with the dietary sodium/potassium ratio in each sex; correlations were better for the ratio than for either sodium or potassium alone. The relationship was apparent over the whole range of blood pressure and dietary intake. A marked age gradient was apparent in men, the regression slope for blood pressure vs sodium/potassium ratio increasing with increasing age, suggesting increasing sensitivity to dietary sodium/potassium ratio with age. Adjusting for intake of other dietary variables, including calories, protein, carbohydrate, saturated fat, alcohol, calcium, and fiber, did not alter the relationships; adjusting for body mass index reduced the strength of the association in women but not in men. These results support the hypothesis that dietary sodium and potassium are related to blood pressure within a population.
A simple specific pattern of chromosomal aberrations at early stages of head and neck squamous cell carcinomas: PIK3CA but not p63 gene as a likely target of 3q26-qter gains.
Authors: Richard Redon, Danièle Muller, Krishna Caulee, Kristell Wanherdrick, Joseph Abecassis, Stanislas du Manoir
Journal: Cancer Research (2001)

Low-grade head and neck squamous cell carcinomas without lymph node involvement or distant metastasis (N(0)M(0)) were screened for chromosomal imbalances by comparative genomic hybridization (CGH). pT(1-2) tumors contain a low number of aberrations (average number, 4.3; 15 cases), in contrast to pT(3) tumors (average number, 11.8; 6 cases), and exhibit a specific CGH pattern, affecting three chromosomes: partial or total 3q gain and/or 3p loss (73% of cases), 8q gain (47%), and 11q13 gain (27%). Thus, these changes represent early events in the pathogenesis of low-grade tumors. Cytogenetic exploration of chromosome 3 aberrations in head and neck cell lines suggests that the formation of an isochromosome 3q is one intermediate mechanism leading to 3p losses and/or 3q gains. On the long arm of chromosome 3, most of tumors exhibit low-level gains of large segments, involving systematically the 3q26-qter area, but with two alternative smallest region overlaps at 3q26 and 3q28-qter. We decided to refine the mapping of 3q26-qter gains by using fluorescence in situ hybridization on tumor nuclei, with clones containing two outstanding positional and functional candidate genes, PIK3CA and p63, located respectively at 3q26 and at 3q28. Although PIK3CA or p63 were preferentially gained in few cases (4 of 45), both genes were over-represented in 27 of 45 low-grade N(0)M(0) carcinomas analyzed by CGH or fluorescence in situ hybridization. To evaluate the relative contribution of PIK3CA and p63 in the pathogenesis of head and neck carcinomas displaying a 3q gain, we measured their respective transcription levels in tumors with previously determined gene copy number. DNp63, the predominant p63 transcript, is overexpressed in tumors compared with normal tissues, but its expression level is independent to gene copy number. In contrast, a significant PIK3CA overexpression is associated with increased gene dosage. These results indicate that PIK3CA, contrary to DNp63, may participate to the progression of head and neck tumors consequent to a low-level 3q over-representation. Interestingly, survival analysis using CGH suggested, in accordance with previous data, that 3q26 gain, the locus of PIK3CA, could predict clinical outcome for early disease tumors. This prompts us to pursue 3q26 (or PIK3CA) prognostic evaluation in a larger population of head and neck squamous cell carcinomas.
The Molecular Basis of Human Cancer
Authors: D.J. Kerr
Journal: Annals of Oncology (2002)

As a new age of medicine is ushered in by the human genome project, it behoves us to understand the broad potential that new molecular technologies will bring to definitions of novel prognostics and therapeutics for a range of different cancers. The Molecular Basis of Human Cancer is a new text book that sets out to capture recent advances in molecular biology techniques, which have substantially increased our ability to detect and characterise genetic defects in human cells. The structure of the book is fairly conventional, with an excellent scene-setting chapter that provides a clear description of widely applied methodologies. This is followed by sections on general aspects of molecular carcinogenesis, mechanisms of mutations and aetiological studies demonstrating how a variety of different carcinogens interact with the genome. The tumour-specific chapters are well written and will attract those with interests in particular tumour-types. The colorectal chapter is especially well written, focussing on how the genetic alterations lead to changes in signal transduction pathways, which underpin disordered growth regulation. All chapters are extensively referenced (probably providing too much information for the more casual clinical reader). There are some omissions, notably around gynaecological cancer, and perhaps sarcomas, each of which can be used to illustrate particular aspects of molecular carcinogenesis. Overall, the book is well written and should be useful to fellows just about to enter the laboratory to undertake a period of molecular research, and for those established clinicians who require a detailed update on the contribution that molecular biology has made to cancer research.
Skeletal muscle weakness, exercise tolerance and physical activity in adults with cystic fibrosis
Authors: T. Troosters, D. Langer, B. Vrijsen, J. Segers, K. Wouters, W. Janssens, R. Gosselink, M. Decramer, L. Dupont
Journal: European Respiratory Journal (2008)

The aim of the present study was to investigate the prevalence of muscle weakness and the importance of physical inactivity in cystic fibrosis (CF), and its relationship to exercise tolerance and muscle strength. Exercise tolerance, skeletal and respiratory muscle strength were studied in a group of 64 adults with CF (age 26+/-8 yrs, FEV(1 % predicted) 65+/-19) and in 20 age-matched controls. Physical activity (PA) was assessed in 20 patients and all controls. Quadriceps muscle weakness was present in 56% of the patients. Peak oxygen uptake and 6-min walking distance were below normal in 89 and 75% of patients, respectively. Respiratory muscle strength was normal. The differences remained after correcting for PA. Quadriceps force was correlated to the 6-min walking distance but not to peak oxygen uptake. "Mild" PA (>3 metabolic equivalents (METS)) and the number of steps overlapped with controls, but CF patients had less moderate PA (>4.8 METS). Moderate PA was related to peak oxygen uptake and quadriceps force. Skeletal muscle weakness and exercise intolerance are prevalent in cystic fibrosis. Physical inactivity is a factor significantly contributing to exercise tolerance and skeletal muscle force in adults with cystic fibrosis, but these impairments are in excess to that expected from physical inactivity only.
A Functional Polymorphism in the <b> <i>EGF</i> </b> Gene Is Found with Increased Frequency in Glioblastoma Multiforme Patients and Is Associated with More Aggressive Disease
Authors: Deb A. Bhowmick, Zhengping Zhuang, Scott D. Wait, Robert J. Weil
Journal: Cancer Research (2004)

Abstract Glioblastoma multiforme, the most aggressive form of primary brain tumor in adults, is nearly universally fatal, with 5-year survivals of &amp;lt;5% (P. Kleihues and W. K. Cavenee, eds., pp. 1–314, Lyon: IARC, 2000). Alterations in the epidermal growth factor receptor (EGFR) are common events in many glioblastoma. We hypothesized that a polymorphism in the 5′-untranslated region of the epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role in the genesis of these malignant gliomas. We find that patients with the GA or GG genotype have higher tumoral levels of EGF, irrespective of EGFR status, that they are more likely to recur after surgery, and that they have a statistically significant shorter overall progression-free survival than patients with the AA genotype. These findings suggest that a single nucleotide polymorphism in EGF may play a role in the formation of glioblastomas, is a useful and powerful prognostic marker for these patients, and may be a target for tumor therapy.