tbuckley/cabot-search huggingface dataset:
Positron emission tomography scanning is not superior to whole body multidetector helical computed tomography in the preoperative staging of colorectal cancer
Authors: H Furukawa
Journal: Gut (2005)

The role of positron emission tomography with the glucose analogue [18F] fluoro-2-deoxy-D-glucose (FDG-PET) in the initial staging of disease in patients with primary colorectal cancer (CRC) has not been adequately assessed.To evaluate the additional value of FDG-PET as a staging modality, complementary to routine multidetector row computed tomography (MDCT) in patients with CRC.Forty four patients with CRC underwent preoperative MDCT and FDG-PET. The accuracy of intraoperative macroscopic staging was also investigated compared with histopathological diagnosis. All FDG-PET images were evaluated with respect to detectability of the primary tumour, lymph node involvement, and distant metastases. Both MDCT and FDG-PET diagnoses and treatment plan were compared with surgical and histopathological results.Thirty seven patients underwent surgery. Tumour detection rate was 95% (42/44) for MDCT, 100% (44/44) for FDG-PET, and 100% (37/37) for intraoperative macroscopic diagnosis. Pathological diagnosis of T factor was T1 in five, T2 in four, T3 in 24, and T4 in four cases. Concordance rate with pathological findings of T factor was 57% (21/37) for MDCT and 62% (23/37) for macroscopic diagnosis. Lymph node involvement was pathologically positive in 19 cases. Regarding N factor, overall accuracy was 62% (23/37) for MDCT, 59% (22/37) for FDG-PET, and 70% (26/37) for macroscopic diagnosis. For all 44 patients, FDG-PET findings resulted in treatment changes in only one (2%) patient.FDG-PET is not superior to routine MDCT in the initial staging of primary CRC.
Comparison of olopatadine nasal spray 0.6%, placebo and fluticasone propionate 0.05% in patients with Seasonal Allergic Rhinitis (SAR) symptoms
Authors: D.L. Spangler, R. Berkowitz, S. Shaver, C. Lutz, D. Bazelmans, G.M. Wall, M. Brubaker, M. Drake, L.G. Hogg, K. Crenshaw
Journal: Journal of Allergy and Clinical Immunology (2005)
Social and lifestyle characteristics and burden of ill-health associated with self-reported hearing and vision impairments in older men in the British community: a cross-sectional study
Authors: Ann E M Liljas, S Goya Wannamethee, Olia Papacosta, Kate Walters, Lucy T Lennon, Livia A Carvalho, Sheena E Ramsay
Journal: The Lancet (2014)
An Address on Disease of the Heart in Children
Authors: J. M. Bruce
Journal: BMJ (1890)

PRESIDENT AND GENTLEMEN,-Disease of the heart as it occurs in the child possesses so many features of special interest that we feel justified in discussing it apart from-indeed as dis- tinguished from-disease of the heart in the adult.The very anatomy and physiology of the circulation are peculiar in young subjects.The causes of disease incident on the puerile heart are
Functional proteomics characterization of residual triple-negative breast cancer after standard neoadjuvant chemotherapy
Authors: J. Sohn, K.A. Do, S. Liu, H. Chen, G.B. Mills, G.N. Hortobagyi, F. Meric-Bernstam, A.M. Gonzalez-Angulo
Journal: Annals of Oncology (2013)
Effects of Once-Daily Angiotensin-Converting Enzyme Inhibition and Calcium Channel Blockade-Based Antihypertensive Treatment Regimens on Left Ventricular Hypertrophy and Diastolic Filling in Hypertension
Authors: Richard B. Devereux, Vittorio Palmieri, Norman Sharpe, Vincent De Quattro, Jonathan N. Bella, Giovanni de Simone, J. Findlay Walker, Rebecca T. Hahn, Björn Dahlöf
Journal: Circulation (2001)

The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)).An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS).Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.
A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists
Authors: Martin C. Michel, Carolyn Foster, Hans R. Brunner, Lisheng Liu
Journal: Pharmacological Reviews (2013)

Angiotensin II type 1 receptor antagonists (ARBs) have become an important drug class in the treatment of hypertension and heart failure and the protection from diabetic nephropathy. Eight ARBs are clinically available [azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan]. Azilsartan (in some countries), candesartan, and olmesartan are orally administered as prodrugs, whereas the blocking action of some is mediated through active metabolites. On the basis of their chemical structures, ARBs use different binding pockets in the receptor, which are associated with differences in dissociation times and, in most cases, apparently insurmountable antagonism. The physicochemical differences between ARBs also manifest in different tissue penetration, including passage through the blood-brain barrier. Differences in binding mode and tissue penetration are also associated with differences in pharmacokinetic profile, particularly duration of action. Although generally highly specific for angiotensin II type 1 receptors, some ARBs, particularly telmisartan, are partial agonists at peroxisome proliferator-activated receptor-<i>γ</i>. All of these properties are comprehensively reviewed in this article. Although there is general consensus that a continuous receptor blockade over a 24-hour period is desirable, the clinical relevance of other pharmacological differences between individual ARBs remains to be assessed.
Performance of an A1C and Fasting Capillary Blood Glucose Test for Screening Newly Diagnosed Diabetes and Pre-Diabetes Defined by an Oral Glucose Tolerance Test in Qingdao, China
Authors: Xianghai Zhou, Zengchang Pang, Weiguo Gao, Shaojie Wang, Lei Zhang, Feng Ning, Qing Qiao
Journal: Diabetes Care (2009)

OBJECTIVE The study's goal was to evaluate the performance of A1C and fasting capillary blood glucose (FCG) tests as mass screening tools for diabetes and pre-diabetes, as determined by the standard oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Data from 2,332 individuals aged 35–74 years who participated in a population-based cross-sectional diabetes survey in Qingdao, China, were analyzed. A 2-h 75-g OGTT was used to diagnose diabetes. The performance of A1C and FCG was evaluated against the results of the OGTTs by using receiver operating characteristic curve (ROC) analysis. RESULTS The prevalence of newly diagnosed diabetes and pre-diabetes (impaired fasting glucose and/or impaired glucose tolerance) was 11.9 and 29.5%, respectively. For subjects with newly diagnosed diabetes, the area under the ROC curve was 0.67 for A1C and 0.77 for FCG (P &amp;lt; 0.01) in men and 0.67 and 0.75 (P &amp;lt; 0.01) in women, whereas for pre-diabetes, these values were 0.47 and 0.64 (P &amp;lt; 0.001) in men and 0.51 and 0.65 (P &amp;lt; 0.001) in women. At the optimal A1C cutoff point of ≥5.6% for newly diagnosed diabetes, sensitivities (specificities) were 64.4% (61.6%) for men and 62.3% (63.3%) for women. CONCLUSIONS As a screening tool for newly diagnosed diabetes and pre-diabetes, the FCG measurement performed better than A1C in this general Chinese population.
TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1
Authors: B. Doleschal, U. Primessnig, G. Wolkart, S. Wolf, M. Schernthaner, M. Lichtenegger, T. N. Glasnov, C. O. Kappe, B. Mayer, G. Antoons, F. Heinzel, M. Poteser, K. Groschner
Journal: Cardiovascular Research (2015)

TRPC3 is a non-selective cation channel, which forms a Ca2+ entry pathway involved in cardiac remodelling. Our aim was to analyse acute electrophysiological and contractile consequences of TRPC3 activation in the heart. We used a murine model of cardiac TRPC3 overexpression and a novel TRPC3 agonist, GSK1702934A, to uncover (patho)physiological functions of TRPC3. GSK1702934A induced a transient, non-selective conductance and prolonged action potentials in TRPC3-overexpressing myocytes but lacked significant electrophysiological effects in wild-type myocytes. GSK1702934A transiently enhanced contractility and evoked arrhythmias in isolated Langendorff hearts from TRPC3-overexpressing but not wild-type mice. Interestingly, pro-arrhythmic effects outlasted TRPC3 current activation, were prevented by enhanced intracellular Ca2+ buffering, and suppressed by the NCX inhibitor 3′,4′-dichlorobenzamil hydrochloride. GSK1702934A substantially promoted NCX currents in TRPC3-overexpressing myocytes. The TRPC3-dependent electrophysiologic, pro-arrhythmic, and inotropic actions of GSK1702934A were mimicked by angiotensin II (AngII). Immunocytochemistry demonstrated colocalization of TRPC3 with NCX1 and disruption of local interaction upon channel activation by either GSK1702934A or AngII. Cardiac TRPC3 mediates Ca2+ and Na+ entry in proximity of NCX1, thereby elevating cellular Ca2+ levels and contractility. Excessive activation of TRPC3 is associated with transient cellular Ca2+ overload, spatial uncoupling between TRPC3 and NCX1, and arrhythmogenesis. We propose TRPC3-NCX micro/nanodomain communication as determinant of cardiac contractility and susceptibility to arrhythmogenic stimuli.
Diagnostic Applications of High-Throughput DNA Sequencing
Authors: Scott D. Boyd
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Advances in DNA sequencing technology have allowed comprehensive investigation of the genetics of human beings and human diseases. Insights from sequencing the genomes, exomes, or transcriptomes of healthy and diseased cells in patients are already enabling improved diagnostic classification, prognostication, and therapy selection for many diseases. Understanding the data obtained using new high-throughput DNA sequencing methods, choices made in sequencing strategies, and common challenges in data analysis and genotype-phenotype correlation is essential if pathologists, geneticists, and clinicians are to interpret the growing scientific literature in this area. This review highlights some of the major results and discoveries stemming from high-throughput DNA sequencing research in our understanding of Mendelian genetic disorders, hematologic cancer biology, infectious diseases, the immune system, transplant biology, and prenatal diagnostics. Transition of new DNA sequencing methodologies to the clinical laboratory is under way and is likely to have a major impact on all areas of medicine.
Activity and Risk of Coronary Heart Disease
Authors: L. Julian Haywood
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The article entitled "Leisure-Time Physical Activity Levels and Risk of Coronary Heart Disease and Death" from the Multiple Risk Factor Intervention Trial<sup>1</sup>raises important issues. The "treatment effect" of a higher level of physical activity seems to be well supported by the data. However, prior studies have shown that physical activity that is heavy enough to produce a training effect results in an increase in left ventricular mass and a reduction of resting pulse rates. In individuals with normal coronary blood flow, these factors should be offsetting. In those with a high risk of developing a coronary event, blood flow might not be adequate for an increase in left ventricular mass. Was the level of physical activity as estimated in this trial in the high-activity group sufficient to produce a training effect and therefore to potentially increase left ventricular mass? Were any measurements taken that might
Explaining differences in English hospital death rates using routinely collected data
Authors: B. Jarman, S. Gault, B. Alves, A. Hider, S. Dolan, A. Cook, B. Hurwitz, L. I Iezzoni
Journal: BMJ (1999)

To ascertain hospital inpatient mortality in England and to determine which factors best explain variation in standardised hospital death ratios.Weighted linear regression analysis of routinely collected data over four years, with hospital standardised mortality ratios as the dependent variable.England.Eight million discharges from NHS hospitals when the primary diagnosis was one of the diagnoses accounting for 80% of inpatient deaths.Hospital standardised mortality ratios and predictors of variations in these ratios.The four year crude death rates varied across hospitals from 3.4% to 13.6% (average for England 8.5%), and standardised hospital mortality ratios ranged from 53 to 137 (average for England 100). The percentage of cases that were emergency admissions (60% of total hospital admissions) was the best predictor of this variation in mortality, with the ratio of hospital doctors to beds and general practitioners to head of population the next best predictors. When analyses were restricted to emergency admissions (which covered 93% of all patient deaths analysed) number of doctors per bed was the best predictor.Analysis of hospital episode statistics reveals wide variation in standardised hospital mortality ratios in England. The percentage of total admissions classified as emergencies is the most powerful predictor of variation in mortality. The ratios of doctors to head of population served, both in hospital and in general practice, seem to be critical determinants of standardised hospital death rates; the higher these ratios, the lower the death rates in both cases.
The Soluble VEGF Receptor sFlt1 Contributes to Endothelial Dysfunction in CKD
Authors: Giovana S. Di Marco, Stefan Reuter, Uta Hillebrand, Susanne Amler, Maximilian König, Etienne Larger, Hans Oberleithner, Eva Brand, Hermann Pavenstädt, Marcus Brand
Journal: Journal of the American Society of Nephrology (2009)

Endothelial dysfunction contributes to the increased cardiovascular risk that accompanies CKD. We hypothesized that the soluble VEGF receptor 1 (sFlt-1), a VEGF antagonist, plays a role in endothelial dysfunction and decreased angiogenesis in CKD. We enrolled 130 patients with CKD stages 3 to 5 and 56 age- and gender-matched control patients. Plasma sFlt-1 levels were higher in patients with CKD and, after multivariate regression analyses, exclusively associated with renal function and levels of vWF, a marker of endothelial dysfunction. Compared with serum from control patients, both recombinant sFlt-1 and serum from patients with CKD had antiangiogenic activity in the chick chorioallantoic membrane (CAM) assay, induced endothelial cell apoptosis in vitro, and decreased nitric oxide generation in two different endothelial cell lines. Pretreating the sera with an antibody against sFlt-1 abrogated all of these effects. Furthermore, we observed increased sFlt1 levels in 5/6-nephrectomized rats compared with sham-operated animals. Finally, using real-time PCR and ELISA, we identified monocytes as a possible source of increased sFlt-1 in patients with CKD. Our findings show that excess sFlt-1 associates with endothelial dysfunction in CKD and suggest that increased sFlt-1 may predict cardiovascular risk in CKD.
Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
Authors: Chau Dang, Hao Guo, Julie Najita, Denise Yardley, Kelly Marcom, Kathy Albain, Hope Rugo, Kathy Miller, Matthew Ellis, Iuliana Shapira, Antonio C. Wolff, Lisa A. Carey, Beverly Moy, John Groarke, Javid Moslehi, Ian Krop, Harold J. Burstein, Clifford Hudis, Eric P. Winer, Sara M. Tolaney
Journal: JAMA Oncology (2015)

Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer.To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer.In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years.Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year.Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported.Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%.Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.
Effects of Angiogenesis Inhibitors on Vascular Network Formation by Human Endothelial and Melanoma Cells
Authors: D. W. J. van der Schaft, R. E. B. Seftor, E. A. Seftor, A. R. Hess, L. M. Gruman, D. A. Kirschmann, Y. Yokoyama, A. W. Griffioen, M. J. C. Hendrix
Journal: JNCI Journal of the National Cancer Institute (2004)

Endothelial cells involved in vasculogenesis and angiogenesis are key targets in cancer therapy. Recent evidence suggests that tumor cells can express some genes typically expressed by endothelial cells and form extracellular matrix-rich tubular networks, phenomena known as vasculogenic mimicry. We examined the effects of three angiogenesis inhibitors (i.e., anginex, TNP-470, and endostatin) on vasculogenic mimicry in human melanoma MUM-2B and C8161 cells and compared them with their effects in human endothelial HMEC-1 and HUVEC cells. Anginex, TNP-470, and endostatin markedly inhibited vascular cord and tube formation by HMEC-1 and HUVEC cells in vitro, whereas tubular network formation by MUM-2B and C8161 cells was relatively unaffected. Endothelial cells expressed higher mRNA and protein levels for two putative endostatin receptors, alpha5 integrin and heparin sulfate proteoglycan 2, than melanoma cells, suggesting a mechanistic basis for the differential response of the two cell types to angiogenesis inhibitors. These findings may contribute to the development of new antivascular therapeutic agents that target both angiogenesis and tumor cell vasculogenic mimicry.
Class II-Associated Invariant Chain Peptide Expression on Myeloid Leukemic Blasts Predicts Poor Clinical Outcome
Authors: Martine E. D. Chamuleau, Yuri Souwer, S. Marieke van Ham, Adri Zevenbergen, Theresia M. Westers, Johannes Berkhof, Chris J. L. M. Meijer, Arjan A. van de Loosdrecht, Gert J. Ossenkoppele
Journal: Cancer Research (2004)

Abstract Effective antitumor responses need the activation of CD4+ T cells. MHC class II antigen presentation requires the release of class II-associated invariant chain peptide (CLIP) from the antigen-binding site. In antigen-presenting cells, human leukocyte antigen DM (HLA-DM; abbreviated DM in this article) catalyzes CLIP dissociation. In B cells, HLA-DO (DO) down-modulates DM function. Cell surface CLIP:HLA-DR (DR) ratio correlates to DO:DM ratio and the efficacy of antigen presentation. We examined 111 blood and bone marrow samples of patients with newly diagnosed acute myeloid leukemia (AML) for the expression of CLIP, DR, DM, and DO by flow cytometry. Patients with DR+/CLIP− blasts had a significant longer disease-free survival than patients with DR+/CLIP+ blasts. DO, until now believed to be restricted to lymphoid cells, could be demonstrated at protein level as well as by reverse transcription-PCR. DO:DM ratio correlated to CLIP:DR ratio, suggesting that, unlike in other antigen-presenting cells of the nonlymphoid cell type, both DO and DM mediate regulation of CLIP expression in AML blasts. We hypothesize that DR+/CLIP− AML blasts are able to present leukemia-specific antigens to CD4+ T helper cells initiating an effective and long-lasting antitumor response resulting in a prolonged disease-free survival.
Haemolysis induced by ascorbic acid in paroxysmal nocturnal haemoglobinuria
Authors: Norihiro Iwamoto, Tatsuya Kawaguchi, Kentaro Horikawa, Shoichi Nagakura, Michihiro Hidaka, Tadashi Kagimoto, Kiyoshi Takatsuki, Hideki Nakakuma
Journal: The Lancet (1994)