tbuckley/cabot-search huggingface dataset:
Abstract 1454: Targeted Molecular Imaging Probes For <i>In Vivo</i> MR Detection Of Atherosclerotic Lesions Using Antibodies Against Oxidized Low Density Lipoprotein
Authors: Karen C Briley-Saebo, Willem Mulder, Peter X Shaw, Seung-Hyuk Choi, Venkatesh Mani, Sotirios Tsimikas, Zahi A Fayad
Journal: Circulation (2007)

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the initiation, progression and destabilization of atherosclerotic plaque. Molecular imaging probes that target OxLDL may allow in vivo detection of vulnerable plaques. In this study, magnetic resonance imaging (MRI) was used to detect atherosclerotic lesions in apolipoprotein deficient mice (ApoE−/−) using micelles comprised of gadolinium lipids, fluorescent rhodamine, PEG-lipids, and MDA2, a murine monoclonal antibody that binds malondialdehyde (MDA) lysine epitopes present in OxLDL. Materials and Results: Untargeted micelles, MDA2-labeled micelles and nonspecific polyclonal IgG micelles were prepared and characterized with respect to OxLDL binding capacity, pharmacokinetics, and biodistribution in wild type (WT) and ApoE−/− mice. MR imaging was performed at 9.4T over a 3-week interval after administration of 0.075 mmol Gd/kg micelles. MDA2 increased the micelle size, blood half-life, and MR efficacy relative to untargeted and IgG-micelles. Maximal plaque enhancement (&gt;125%) was observed 72 hours post MDA2-micelle injection (Figure ). Untargeted and IgG-micelles did not exhibit significant wall enhancement at any of the time points studied. Confocal microscopy revealed that MDA2-micelles accumulate within foam cells associated with atherosclerotic plaque. WT mice showed no significant MR wall enhancement for any of the micelles studied. Conclusions: MR imaging using MDA2-micelles demonstrates specific targeting of OxLDL and foam cells and provides excellent MR image quality. This study suggests that it may be feasible to image similar atherosclerotic lesions in humans with MRI.
Abstract 16849: Mice Lacking Cyp8b1 Have Dramatically Improved Cardio-Metabolic Profile Due to Alterations in Bile Acid Profile
Authors: Saj Parathath, Raymond Rosa, Judith N Gorski, Sheng-ping Wang, Karni Schlessinger, Kithsiri Herath, Stephen Previs, Jose M Castro-Perez, Kenny K Wong
Journal: Circulation (2014)

Bile acids are important amphoteric biomolecules that can serve in a variety of biological functions including; fat emulsification and molecular signaling via nuclear receptors. Bile acid synthesis mediated via CYP7A1is the primary route for excess cholesterol elimination. The major bile acids in humans are cholic acid (CA) and chenodeoxycholic acids (CDCA). CYP8B1 is part of the family of CYP P450 enzymes. CYP8B1 is expressed in the endoplasmic reticulum as a membrane protein which is responsible for the catalysis of 7α-hydroxy-4cholesten-3-one (7-HCO) into 7-12- α-dihydroxy-4-cholesten-3-one (7-12 diHCO) both being rate-limiting step intermediates of bile acid (BA) synthesis. We hypothesized that CYP8B1 KO mice would have several favorable cardiometabolic changes due to improved BA profile. CYP8B1 KO mice lack CA resulting in a 50% decrease in cholesterol absorption as determined by dual isotope kinetics. These mice also have increased fecal excretion of total-bile acids (~300%) and cholesterol (40%). E...
Abstract 1902: Prevalence Of Atherosclerosis in Middle-age: Results from the Asklepios Study in 2524 Subjects Free from Overt Cardiovascular Disease
Authors: Ernst Rietzschel, Marc De Buyzere, Dirk De Bacquer, Patrick Segers, Sofie Bekaert, Guy De Backer, Thierry C Gillebert
Journal: Circulation (2006)

Background : Ultrasonographic atherosclerosis phenotypes are currently advocated as intermediate phenotypes in risk prediction, in clinical trials and in biomarker discovery. Nevertheless data on the prevalence of atherosclerotic phenotypes such as intima-media thickening (IMT>0.9mm) or plaque at different sites (carotid, femoral) within single population databases are limited.

 Methods : The 2524 participants (1301 F) of the ASKLEPIOS Study are a representative cohort of 35–55 year-old subjects (median age 45.9 y) free from overt cardiovascular disease at baseline. Extensive physical and laboratory evaluations included echography (GE/Vingmed Vivid 7; all single observer, device and site). Phenotypes studied include: IMT, plaque (Mannheim criteria) at both carotid and femoral arteries.

 Results : Using conservative definitions (limiting IMT measurement to high-shear areas): 40% of subjects had atherosclerosis (femoral 30%; carotid 22%) with obvious age/gender dependency (see fig[⇓][1].). Males have a prevalence increase of 20%/5 years; females of 10%/5 years. Prevalence data are highly dependent on the definition used, using less conservative definitions including low shear areas of the vasculature for IMT measurement would dramatically increase prevalence of atherosclerosis to >80% even in subjects <40 years.

 Conclusions : Ultrasound evidence for atherosclerosis (IMT or plaque) is very common in apparently healthy 35–55 year old subjects, with pronounced age and gender gradients. Expanding current definitions of atherosclerosis to include low-shear wall thickening yields prevalence data effectively invalidating its discriminative use as a risk marker.



   ![][2]  [1]: #graphic-1
 [2]: /embed/graphic-1.gif
Abstract 14570: Direct Comparison of CMR Dobutamine Stress Wall Motion Analysis and Perfusion with Adenosine Perfusion in Patients after Bypass Surgery
Authors: Christoph Klein, Rolf Gebker, Sebastian Kelle, Bernhard Schnackenburg, Stephan Dreysse, Eckard Fleck
Journal: Circulation (2010)

Introduction:  Dobutamine and adenosine stress are the two methods most often used in cardiac magnetic resonance (CMR) for the diagnosis of ischemia and most centers use adenosine perfusion due to its ease to perform. Both methods have demonstrated good Results in patients after coronary artery bypass graft (CABG). However, a direct comparison has not been examined.   Purpose:  Comparison of the diagnostic accuracy of wall motion analysis (DSMR) and perfusion (DSPERF) with dobutamine stress with adenosine perfusion (APERF).   Methods:  Sixty eight patients (57 men, 65±8 years, BMI 28.7±3.3) after CABG underwent CMR imaging on two appointments. 1) LV-function, DSMR (10–40μg/kg/min + 2mg atropine if needed until target heart rate) imaging (SSFP) of 3 short axis (apical, medial, basal) and 3 long axis views at each stress level. Perfusion imaging of 3 short axis (SSFP, TR/TE 2.8 ms/1.4 ms, FA 50°, SENSE-factor 3.0) were acquired every second heart beat during dobutamine stress at maximal stress level with a contrast bolus of 0.1mmol/kg Gd-DTPA. Late gadolinium enhancement (LGE) imaging (3D inversion recovery technique, TE/TR 2.8/6.6, FA 15°) 10min after additional 0.1mmol/kg Gd-DTPA. 2) Adenosine and rest perfusion (140 μg/min/kg body weight) (SSFP, TE/TR 2.7/1.4, FA 50°, 3 short axis per heart beat) using a 0.05mmol/kg contrast bolus of Gd-DTPA. Invasive coronary angiography served as the reverence. Images were analyzed visually using the standard 16 segment model. Significant stenosis was defined as >50% in a bypass graft or a native vessel ≥ 2mm diameter in areas without 100% transmural LGE.   Results:  Prevalence of angiographically significant stenosis was in 63% of patients, after adjustment of the presence of LGE in 42%. Surgery was performed 9.5±6.6 years before CMR. LGE was present in 68% of patients. Sensitivity, specificity and diagnostic accuracy are shown in table 1.   Conclusions:  DSMR was the best test for the detection of ischemia in patients after bypass surgery and outperforms adenosine stress perfusion. The addition of DSMR perfusion increases sensitivity, but decreases diagnostic accuracy. Table 1 Sensitivity Specificity Diagnostic accuracy DSMR 88% 96% 93% DSPERF 76% 73% 75% DSMR + DSPERF 94% 73% 83% APERF 75% 91% 85%
Abstract P123: Vasopressin, but not Norepinephrine, causes Ventriculoarterial Mismatch in Experimental Post Ischemic Cardiogenic Shock
Authors: Ole-Jakob How, Assami Røsner, Petter Gjessing, Stig E Hermansen, Truls Myrmel
Journal: Circulation (2008)

Introduction In agreement with existing guidelines, inotropic and vasopressor support is given routinely in cardiogenic shock (CS). However, there is a lack of scientific evidence supporting the efficacy and safety of such treatment. Hypothesis Vasoconstrictors given in cardiogenic shock will increase the ventriculoarterial mismatch and thus lead to reduced cardiac output Methods In a closed chest pig model we tested the inodilator (dobutamine, Dobut) alone and combined with either an inoconstrictor (norepinephrine, NE) or a pure vasopressor (arginine vasopressin, AVP). In anesthetized animals, CS was induced by coronary microembolization under fluoroscopic guidance. Hemodynamic indices were obtained by Swan-Ganz catheters, left ventricular pressure-volume catheters and echocardiography, and the ventriculoarterial coupling calculated. Results In the normal heart, Dobut (2ug/kg/min) enhanced ventriculoarterial energy transfer, shown as a decreased Ea/Ees (ratio of arterial and ventricular elastance), 1.0 ± 0.1 to 0.8 ± 0.1, and an increased preload recruitable stroke work (PRSW), 53 ± 5 to 63 ± 2. This was further enhanced by NE (100 ng/kg/min) to 0.7 ± 0.1 and 79 ± 6. In contrast, adding AVP (0.001 u/kg/min) resulted in an increased Ea/Ees (1.0 ± 0.1) and decreased PRSW (56 ± 8) compared to Dobut alone (a two fold increase in systemic vascular resistance (SVR), concomitant with no elevation in contractility). In post ischemic CS, energy transfer from the ventricle to the arterial system (Ea/Ees 1.8 ± 0.2, PRSW 26 ± 2 and Ejection fraction 42 ± 6 %) was partly restored by Dobut (1.4 ± 0.2, 46 ± 2 and 47 ± 6%) unaffected by further adding NE (1.5 ± 0.2, 53 ± 2 and 45 ± 5%), but impaired after adding AVP (2.0 ± 0.1, 43 ± 1 and 34 ± 4%). Consequently, Dobut improved the shock by increasing cardiac output (CO) and SVO2 from 74 ± 3 ml/kg and 37 ± 2% to 103 ± 8 ml/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 ml/kg) and SVO2 (59 ± 4%). In contrast AVP further worsened the shock state by decreasing CO (70 ± 6 ml/kg) and SVO2 (45 ± 5%) compared to Dobut alone. Conclusion A pure afterload increasing substance in acute ischemic hearts with cardiogenic shock aggravate the shock state by causing a ventriculoarterial mismatch.
Renal-Cell Cancer
Authors: H. Grabstald
Journal: CA A Cancer Journal for Clinicians (1966)

A number of tei-ms have been cor rectly and incorrectly applied to this commonest, most significant and ex tremely interesting malignant tumor of renal tubular epithelium.(Figs. 1 and 2.) The terms renal-cell cancer and renal adenocarcinoma al-c both correct and ai'e often used interchangeably.Incidence Renal cancer takes third place among malignant genitourinary tumors occur ring among males, preceded by cancer of the prostate and bladder, respec tively.Among kidney cancers, renal adenocarcinomas account for slightly more than foui'-fifths of the tumors ob served.'-2Renal cancei' represents ap proximately 1.7% of the cancers found among males, and about 1.0% among females.Etiology Etiologic data on renal adenocar cinoma are notable by both their scarc ity and by the large extent to which they are drawn from animal experi mentation.The suggestion that hormones may play a definite role in the causation and/or development of renal adeno Dr. (;rabstald is .1 ssociate A ttendinq Surgeon, Uroloqtc
Minimising the impact of visual impairment
Authors: J. M Carter, N. Markham, W. Birchall, A C Burden, M. L Burden, L. Hayward
Journal: BMJ (1999)

Editor—Margrain’s editorial on minimising the impact of visual impairment is firmly based on the medical model of disability, which locates disability in individuals.1 Disabled people have developed the social model as an accurate description of their life experience, and the World Health Organisation is revising its definition of disability to take this into account.2 The social model locates disability in society; therefore it is society that causes “much individual suffering and economic hardship,” not visual impairment.

The editorial refers to the percentage of visually impaired people who could read normal print before and after the provision of a low vision aid and some training. But if everyone who produced information in print realised that the size of the print (or the use of print) can exclude people from gaining access to the information all information might be fully accessible.

Under the terms of the Disability Discrimination Act 1995, from October 1999 those who offer goods or services to the public are required to take reasonable steps to ensure that disabled people can make use of their services. A code of practice makes specific reference to the provision of documents in larger or clear print, Moon, or Braille; information on computer diskette; information on audiotape; and telephone services to supplement other information.3

For the health sector this means, for example, that hospital and primary care information must be available in formats accessible to everyone. The data given in the editorial about the number of people who are visually impaired indicates how many people potentially face discrimination if providers of goods and services do not produce information that is fully accessible.

The Royal National Institute for the Blind recently reported a survey of health authorities and NHS trusts in Great Britain.4 Of the 326 trusts that responded to a questionnaire, 35% offered general information for patients in large print but only 4% could provide test results in that format. The Royal College of Physicians’ charter for disabled people using hospitals states that “every disabled patient, visitor, or hospital employee has the right to relevant and accessible information, especially about the hospital’s provision for disabled people.”5

The principle of ensuring that disabled people are not marginalised can be applied not only to the provision of information but also to other aspects of minimising the impact of an impairment. From October this will no longer be merely about good practice and equity but about conforming to the law.
Abstract 19016: Angiographic Obstructive Disease Predicted by Calcium Scanning and XECG in Real-World Patients With Stable Chest Complaints
Authors: Admir Dedic, Lisan Neefjes, Gert-Jan ten Kate, Alexia Rossi, Adriaan Moelker, Tjebbe Galema, P.J. de Feyter, Koen Nieman
Journal: Circulation (2010)

Introduction: Catheter (CAG) and computed angiography (CTA) are reliable means for exclusion of obstructive coronary artery disease (CAD), although costly with considerable exposure to radiation an...
Nitroglycerin and Nitric Oxide — A Rondo of Themes in Cardiovascular Therapeutics
Authors: Benjamin S. Steinhorn, Joseph Loscalzo, Thomas Michel
Journal: New England Journal of Medicine (2015)

The development of a wide range of therapeutics based on the nitric oxide signaling pathway has been fueled by keen clinical observation followed by laboratory study and a return to the bedside in an iterative process that is continuing to yield new insights.
Ultrasound treatment for carpal tunnel syndrome
Authors: L. Deliss
Journal: BMJ (1998)

Breast cancer screening: false positive rate is lower in older womenEditor-Werneke and McPherson 1 question the detection rates of cancer observed in the breast screening programme in East Sussex, Brighton, and Hove that we reported in our recent paper. 2 They suggest that these are the result of a high proportion of false positive screens.It is unfortunate that they did not consult us beforehand.The paper gives results of an ongoing study, but the cancers reported are those confirmed by histological examination after surgery, not preliminary suspected cancers at "positive" screens.The statistical programme was not run until some months after the end of the screening period, when all the screening episodes had been completed and the women concerned had been assessed, diagnosed, and operated on as appropriate.The East Sussex area has always tended to have a high detection rate for cancer, possibly because of the local sociodemographic composition of the population, and the rate over this period was higher than in the following year, without being exceptional.The 1995-6 result for the whole South West Thames region was 7.6 women with cancer for every 1000 women screened overall. 3he small study of older women in north London found 14.2 women with cancer per 1000 women screened aged 65-9. 4uring the period reported in our study the recall for assessment rate in women aged 65-7 was 4.6% (95% confidence interval 3.9% to 5.2%) and 6.2% (5.2% to 7.2%) in those aged 68-9, compared with 6.1% (5.8% to 6.4%) in those aged 50-64.Given the higher number of cancers detected this indicates a lower false positive rate in older women.This is to be expected because of the relative ease of interpreting mammograms and decreasing incidence of benign breast lesions in older women. 5 We now have the first year's results from the other two pilot sites, which will be published in due course.They confirm higher detection rates of cancer in older women but similar recall rates.Attendance is also encouragingly high.
Abstract 17056: Telomerase Reverse Transcriptase (TERT) and Endothelial NO Synthase (eNOS) Mediate Vascular Anti-Senescent and Endothelial-Protective Effects of Physical Exercise
Authors: Christian Werner, Tobias Furster, Judith Haendeler, Michael Bohm, Ulrich Laufs
Journal: Circulation (2010)

Background: The prevalence of cardiovascular disease increases with age. Aging on the cellular level depends on the function of telomeres and telomere-associated proteins. Physical exercise reduces...
Chemotactic Factor Inactivation by the Myeloperoxidase-Hydrogen Peroxide-Halide System
Authors: Robert A. Clark, Seymour J. Klebanoff
Journal: Journal of Clinical Investigation (1979)

Polymorphonuclear leukocytes may modulate the acute inflammatory response by the secretion of enzymes capable of inactivating mediators of inflammation. The ability of the myeloperoxidase-H2O2-halide system of the neutrophil to inactivate chemoattractants was examined using both a radioassay and a morphologic assay of chemotaxis. Incubation of either a complement-derived agent, C5a, or a synthetic formyl-methionyl peptide chemoattractant with the myeloperoxidase system for 15 min at 37°C resulted in essentially complete loss of chemotactic activity. Inactivation was dependent on enzymatically active myeloperoxidase, H2O2 or a peroxide-generating enzyme system, and a halide cofactor. It was blocked by agents which inhibit peroxidase (azide) or degrade H2O2 (catalase). Inactivation of chemoattractants was time-dependent, reaching maximal levels within 1-5 min, and temperature-dependent with no significant inactivation occurring at 0°C. H2O2 alone had no significant inactivating ability at concentrations as high as 10 mM, whereas in the presence of myeloperoxidase and a halide, 0.1 μM H2O2 showed significant activity and 10 μM H2O2 caused complete inactivation. On a molar basis, the order of effectiveness of the halide cofactors was Br− > I− > Cl−, although only chloride was fully active at physiologic concentrations. Neutrophils stimulated by phagocytosis or by membraneperturbing agents secrete enzymatic constituents, including myeloperoxidase, and metabolic products such as H2O2. Thus, it is suggested that the myeloperoxidase system acting at an extracellular site serves as an inflammatory control mechanism by virtue of its ability to inactivate neutrophil chemoattractants.
Abstract 5954: Does Sirolimus-Eluting Stent Implantation Lead to an Increased Risk of Stent Fracture?
Authors: Hisashi Umeda, Tomoko Gochi, Mitsuhiro Iwase, Hideo Izawa, Mitsuhiro Yokota, Toyoaki Murohara
Journal: Circulation (2008)

Stent fracture (SF) of sirolimus-eluting stents (SES) has emerged recently in literature and shown to be associated with an increased risk of restenosis. We sought to assess whether the use of SES increases the frequency of SF compared with bare-metal stents (BMS). A consecutive series of 499 lesions of 434 patients undergoing SES implantation (total stent length: 10 to 40 mm) followed by coronary angiography at 6 to 9 months were compared with 137 consecutive patients (147 lesions) treated with BMS (total stent length: 10 to 40 mm) which consists of stent platform of SES. SF was defined as single or multiple stent strut fracture as well as complete separation of stent segments. There were no significant differences in total stent length and the angulation of the lesion between the 2 groups. At follow up, SF occurred in 21 lesions (4.2%) in the SES group and 2 lesions (1.4%) in the BMS group (P=0.129). In-stent restenosis rates were 34.8% (SES; 33.3%, BMS; 50.0%) in lesions with SF and 7.7% (SES; 3.8%, BMS; 20.7%) in lesions without SF (P&lt;0.001). As a result, cumulative rate of major adverse cardiac events at 1 year (death, myocardial infarction, or target lesion revascularization) was higher in patients with SF than in patients without SF (27.3% vs. 12.0%, P=0.035, SES; 25.0% vs. 8.2%, P=0.035, BMS; 50.0% vs. 23.7%, P=0.425). Figure summarizes multivariable predictors of SF. In this model, SES use was not associated with a significantly increased risk of SF at 6 to 9 months. The implantation of stents in tortuous lesion and/or longer lesions covered with longer stents rather than the use of SES may increase the likelihood of SF in this population subset.