tbuckley/cabot-search huggingface dataset:
Characterisation, utilisation and clinical relevance of isolated perfused heart models of ischaemia-induced ventricular fibrillation
Authors: M Curtis
Journal: Cardiovascular Research (1998)

The isolated perfused heart has been used increasingly during the last decade as a model for identifying actions of drugs on ventricular fibrillation (VF) induced by myocardial ischaemia. In addition, it has been used to explore the mechanisms responsible for the initiation and maintenance of VF, the concept of endogenous myocardial protection and the phenomenon of preconditioning. This article is a review of the available data (effects of drugs, sources of variation, comparison with other models and man, etc.) and an attempt to evaluate the possible clinical relevance. For several reasons, it is not possible to make a precise judgement on the absolute value of the model in terms of its ability to accurately predict the effectiveness of drugs in the prevention of sudden cardiac death, the main reason being the lack of a positive control, i.e. a drug with proven effectiveness against sudden cardiac death caused by VF in man. Nevertheless, the means by which one may reliably and reproducibly generate ischaemia-induced VF in different isolated heart preparations, and the factors (such as species, heart rate, perfusion constituents and involved zone size) that determine the incidence of VF are now well documented. Careful selection of species and experimental conditions permits the isolated heart of smaller inexpensive animals to function as a first line model for detecting anti-VF activity of probable relevance to phase 1 arrhythmogenesis (i.e., arrhythmogenesis during the first 30 min of ischaemia). In view of the absence of a clinical template from which to evaluate how well it predicts drug effectiveness in man, this model's clinical relevance, like that of all other preparations and models, can yet be neither accepted nor dismissed. Recent publication patterns suggest an increasing use of the model. Therefore, recommendations are made to facilitate its effective use.
Pre-operative intradermal administration of CpG-B ± GM-CSF in stage I-III melanoma patients arms the sentinel lymph node: evidence for reduced tumor spread
Authors: Mari F van den Hout, Bas D Koster, Rik J Scheper, Rieneke van de Ven, Berbel J Sluijter, Barbara G Molenkamp, Alfons J van den Eertwegh, Paul A van Leeuwen, Petrousjka M van den Tol, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Melanoma cutis is virtually incurable when it has metastasized to distant organs. Unfortunately, there is no safe and effective adjuvant treatment available for early stage patients that may prevent the development of metastasis. Since early melanoma development is accompanied by
Increased Burden of Cardiovascular Disease in Carriers of <i>APOL1</i> Genetic Variants
Authors: Kaoru Ito, Alexander G. Bick, Jason Flannick, David J. Friedman, Giulio Genovese, Michael G. Parfenov, Steven R. DePalma, Namrata Gupta, Stacey B. Gabriel, Herman A. Taylor, Ervin R. Fox, Christopher Newton-Cheh, Sekar Kathiresan, Joel N. Hirschhorn, David M. Altshuler, Martin R. Pollak, James G. Wilson, J.G. Seidman, Christine Seidman
Journal: Circulation Research (2013)

Rationale: Two distinct alleles in the gene encoding apolipoprotein L1 ( APOL1 ), a major component of high-density lipoprotein, confer protection against Trypanosoma brucei rhodesiense infection and also increase risk for chronic kidney disease. Approximately 14% of Americans with African ancestry carry 2 APOL1 risk alleles, accounting for the high chronic kidney disease burden in this population. Objective: We tested whether APOL1 risk alleles significantly increase risk for atherosclerotic cardiovascular disease (CVD) in African Americans. Methods and Results: We sequenced APOL1 in 1959 randomly selected African American participants in the Jackson Heart Study (JHS) and evaluated associations between APOL1 genotypes and renal and cardiovascular phenotypes. Previously identified association between APOL1 genotypes and chronic kidney disease was confirmed ( P =2.4×10 −6 ). Among JHS participants with 2 APOL1 risk alleles, we observed increased risk for CVD (50/763 events among participants without versus 37/280 events among participants with 2 risk alleles; odds ratio, 2.17; P =9.4×10 −4 ). We replicated this novel association of APOL1 genotype with CVD in Women’s Health Initiative (WHI) participants (66/292 events among participants without versus 37/101 events among participants with 2 risk alleles; odds ratio, 1.98; P =8.37×10 −3 ; JHS and WHI combined, P =8.5×10 −5 ; odds ratio, 2.12). The increased risk for CVD conferred by APOL1 alleles was robust to correction for both traditional CVD risk factors and chronic kidney disease. Conclusions: APOL1 variants contribute to atherosclerotic CVD risk, indicating a genetic component to cardiovascular health disparities in individuals of African ancestry. The considerable population of African Americans with 2 APOL1 risk alleles may benefit from intensive interventions to reduce CVD.
Group Health Cooperative — One Coverage-and-Delivery Model for Accountable Care
Authors: Eric B. Larson
Journal: New England Journal of Medicine (2009)

"On January 1, 1947, Group Health Cooperative of Puget Sound began delivering a new kind of healthcare. Consumers paid flat monthly dues for comprehensive care. Members elected the board of trustees and bought bonds to fund new facilities. Doctors and nurses devoted as much energy to promoting wellness as they did to treating illness. Group Health Cooperative's founders believed that health was everybody's business and everybody's right. They prescribed democracy to cure an expensive and inefficient health care system."So reads historian Walt Crowley's description of the Seattle health plan's birth, in his book named for the organization's mission, To . . .
The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection.
Authors: K Aupeix, B Hugel, T Martin, P Bischoff, H Lill, J L Pasquali, J M Freyssinet
Journal: Journal of Clinical Investigation (1997)

The plasma membrane remodeling, including the early transverse redistribution of phosphatidylserine, is a general feature occurring in cells in which a death program has been induced. In most cases, studies of this kind have focused mainly on cells. In this study, we report a clear correlation between the degree of apoptosis induced by a variety of agents in several types of cultured cells and the amount of shed membrane microparticles captured in the corresponding supernatants by insolubilized annexin V, a protein showing a strong affinity for phosphatidylserine. Such particles carry membrane antigens specific of the cells they stem from, and through which capture is also feasible. Homologous circulating microparticles were captured in peripheral blood from individuals with HIV-1 infection. A substantial proportion bore CD4 antigen. In some cases, CD4+ particles could be detected even in the absence of circulating CD4+ T cells, testifying to the presence of such resident cells in lymphoid tissues. These results suggest that shed membrane particles are one of the hallmarks of programmed cell death, of particular interest when the corresponding cells are hardly accessible.
Hemodynamic and metabolic responses to leukotriene C4 in isolated perfused rat liver
Authors: Herbert Krell, Eberhard Dietze
Journal: Hepatology (1989)

Responses of isolated perfused rat liver to leukotriene C 4 were studied in order to assess the mechanisms involved in leukotriene-mediated liver injury. Infusion of leukotriene C 4 (11 and 44 pmoles per min per gm liver weight) into the portal vein resulted in a rise in portal pressure, a decrease in oxygen consumption, an increase in hepatic glucose and lactate efflux and lactate/pyruvate ratio in the perfusate and a small decrease in bile flow. Isoproterenol (1 μ M ) counteracted the effects of leukotriene C 4 on respiration and portal pressure, whereas bile flow and glucose efflux were reversibly stimulated. The same changes were observed upon with-drawal of leukotriene C 4 . The release of glucose was correlated with the increase in oxygen consumption upon both isoproterenol addition and withdrawal of leukotriene C 4 . These results are indicative of leukotriene C 4 -induced microcirculatory redistribution of perfusate flow. Since, in the presence of nitroprusside (50 μ M ), both the effects of leukotriene C 4 and their reversal by isoproterenol were diminished, a vascular site of action can be assumed. Accordingly, the accompanying metabolic responses can be explained by gradual changes in oxygen supply to parts of the liver. Reversibility of the leukotriene C 4 effects and lack of short-term impairment of viability of the isolated liver suggest that leukotriene-mediated liver injury is a long-term effect related to events subsequent to microcirculatory changes.
Effect of ketanserin on proximal and distal coronary constrictor responses to intracoronary infusion of serotonin in patients with stable angina, patients with variant angina, and control patients.
Authors: E P McFadden, C Bauters, J M Lablanche, F Leroy, J G Clarke, M Henry, C Schandrin, G J Davies, A Maseri, M E Bertrand
Journal: Circulation (1992)

BACKGROUND Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.
Statin Toxicity From Macrolide Antibiotic Coprescription
Authors: Sonja Gandhi, Amit X. Garg
Journal: Annals of Internal Medicine (2013)

LettersOctober 15, 2013Statin Toxicity From Macrolide Antibiotic CoprescriptionSonja Gandhi, BSc and Amit X. Garg, MD, PhDSonja Gandhi, BScFrom Western University, London, Ontario, Canada.Search for more papers by this author and Amit X. Garg, MD, PhDFrom Western University, London, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-8-201310150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We disagree that inclusion of a nondrug comparator group would have been useful, because patients with infection who receive antibiotics would be expected to have a different risk for outcomes than those who do not receive antibiotics (and a comparison of the 2 groups would be heavily criticized for confounding by indication). Rather, we recently published another study to reassure readers that the associations that we reported in all probability reflect differences related to the type of macrolide antibiotic coprescribed with a statin (1).In brief, this second study was also conducted using large health care databases in ...Reference1. Fleet JL, Shariff SZ, Bailey DG, Gandhi S, Juurlink DN, Nash DM, et al. Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions. BMJ Open. 2013;3:. [PMID: 23847265] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Western University, London, Ontario, Canada.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1300. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoStatin Toxicity From Macrolide Antibiotic Coprescription Amit M. Patel , Salimah Shariff , David G. Bailey , David N. Juurlink , Sonja Gandhi , Muhammad Mamdani , Tara Gomes , Jamie Fleet , Y. Joseph Hwang , and Amit X. Garg Statin Toxicity From Macrolide Antibiotic Coprescription Houman Farzin , Mai Takematsu , and Robert S. Hoffman Metrics October 15, 2013Volume 159, Issue 8Page: 575KeywordsAcute renal failureAdverse eventsAntibioticsDatabasesDrug administrationDrug interactionsDrugsErythromycinFoodHospitalizationsInformation storage and retrievalPharmacokineticsPhysiciansResearch laboratoriesRespiratory infectionsRhabdomyolysisStatinsToxicityUpper respiratory tract infections ePublished: 15 October 2013 Issue Published: October 15, 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Universal Entitlement to Health Care
Authors: D M Kinzer
Journal: New England Journal of Medicine (1990)

One of the linguistic inventions of Harvard professor John Dunlop was the term "disjointed incrementalism." Dunlop, former U.S. secretary of labor and an expert on conflict resolution, used it frequently in his lectures to describe the American political style in addressing large public issues. Instead of taking them on in their entirety, he pointed out, our political bodies nearly always nibble at them around the edges, dealing only with the piece of the problem that has high public visibility, causes the most political discomfort, or both.Examples of disjointed incrementalism abound in the health field. Back in the 1960s, Medicare . . .
Technetium-99m MDP Bone Scan and MRI Correlation in the Detection of Occult Bone Infarction
Authors: BRIAN EISENBERG, GLENN G. COATES, LARRY R. HOLDER
Journal: Clinical Nuclear Medicine (1994)

A 37-year-old female on prednisone therapy for inflammatory bowel disease had chronic focal knee pain bilaterally for several months. Plain film imaging results were normal. However, Tc-99m MDP bone scintigraphy obtained the same day revealed diffuse increased uptake of radionuclide within the distal femoral metaphases and knees bilaterally. Additional diffuse increased activity was seen in the left tibial plateau, with a second small focal area of activity within the proximal tibial diaphysis. An MRI performed 2 weeks later shows classic bilateral bone infarctions in these regions.
New developments in percutaneous coronary intervention
Authors: J. Gunn
Journal: BMJ (2003)

Percutaneous coronary intervention has become a more common procedure than coronary artery bypass surgery in many countries, and the number of procedures continues to rise. In one day an interventionist may treat four to six patients with complex, multivessel disease or acute coronary syndromes. Various balloons, stents, and other devices are delivered by means of a 2 mm diameter catheter introduced via a peripheral artery. The success rate is over 95%, and the risk of serious complications is low. After a few hours patients can be mobilised, and they are usually discharged the same or the next day. Even the spectre of restenosis is now fading.

The present success of percutaneous procedures is largely because of refinement of our “basic tools” (intracoronary guidewires and low profile balloons), which have greatly contributed to the safety and effectiveness of procedures. However, the greatest technological advance has been in the development of stents. These are usually cut by laser from stainless steel tubes into a variety of designs, each with different radial strength and flexibility. They are chemically etched or electropolished to a fine finish and sometimes coated.

Digital angiography is a great advance over cine-based systems, and relatively benign contrast media have replaced the toxic media used in early angioplasty. Although magnetic resonance and computed tomographic imaging may become useful in the non-invasive diagnosis of coronary artery disease, angiography will remain indispensable to guide percutaneous interventions for the foreseeable future.

View this table:

Interventional devices and their uses



Pre-eminent among new devices is the drug eluting (coated) stent, which acts as a drug delivery device to reduce restenosis. The first of these was the sirolimus coated Cypher stent. Sirolimus is one of several agents that have powerful antimitotic effects and inhibit new tissue growth inside the artery and stent. In a randomised controlled trial (RAVEL) …
FAVORABLE EFFECTS OF L-ARGININE ON ARTERIAL FUNCTION, INFLAMMATORY AND FIBRINOLYTIC PROCESS IN SMOKERS
Authors: Gerasimos Siasos, Dimitris Tousoulis, Charalampos Vlachopoulos, Elias Gialafos, Evaggelos Oikonomou, Aris Plastiras, Marina Zaromitidou, Konstantinos Zisimos, Charalampos Antoniades, Georgia Siasou, Dimitra Papaspiridi, Georgios Marinos, Athanasios G. Papavassiliou, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2010)
Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science
Authors: Richard D. Lane, Lee Ryan, Lynn Nadel, Leslie Greenberg
Journal: Behavioral and Brain Sciences (2014)

Since Freud, clinicians have understood that disturbing memories contribute to psychopathology and that new emotional experiences contribute to therapeutic change. Yet, controversy remains about what is truly essential to bring about psychotherapeutic change. Mounting evidence from empirical studies suggests that emotional arousal is a key ingredient in therapeutic change in many modalities. In addition, memory seems to play an important role but there is a lack of consensus on the role of understanding what happened in the past in bringing about therapeutic change. The core idea of this paper is that therapeutic change in a variety of modalities, including behavioral therapy, cognitive-behavioral therapy, emotion-focused therapy, and psychodynamic psychotherapy, results from the updating of prior emotional memories through a process of reconsolidation that incorporates new emotional experiences. We present an integrated memory model with three interactive components - autobiographical (event) memories, semantic structures, and emotional responses - supported by emerging evidence from cognitive neuroscience on implicit and explicit emotion, implicit and explicit memory, emotion-memory interactions, memory reconsolidation, and the relationship between autobiographical and semantic memory. We propose that the essential ingredients of therapeutic change include: (1) reactivating old memories; (2) engaging in new emotional experiences that are incorporated into these reactivated memories via the process of reconsolidation; and (3) reinforcing the integrated memory structure by practicing a new way of behaving and experiencing the world in a variety of contexts. The implications of this new, neurobiologically grounded synthesis for research, clinical practice, and teaching are discussed.
Can neural models of cognition benefit from the advantages of connectionism?
Authors: Friedrich T. Sommer, Pentti Kanerva
Journal: Behavioral and Brain Sciences (2006)

Cognitive function certainly poses the biggest challenge for computational neuroscience. As we argue, past efforts to build neural models of cognition (the target article included) had too narrow a focus on implementing rule-based language processing. The problem with these models is that they sacrifice the advantages of connectionism rather than building on them. Recent and more promising approaches for modeling cognition build on the mathematical properties of distributed neural representations. These approaches truly exploit the key advantages of connectionism, that is, the high representational power of distributed neural codes and similarity-based pattern recognition. The architectures for cognitive computing that emerge from these approaches are neural associative memories endowed with additional mapping operations to handle invariances and to form reduced representations of combinatorial structures.
Abstract P4-11-13: A Multi-Institutional Assessment of the Feasibility, Implementation, and Early Clinical Results with Noninvasive Image-Guided Breast Brachytherapy for Tumor Bed Boost
Authors: S Hamid, S Ackerman, D Arthur, R Benda, S Cavanaugh, R Kuske, B Prestidge, C Quiet, S Sha, DE. Wazer
Journal: Cancer Research (2010)

Abstract Background: Noninvasive image-guided breast brachytherapy (NIIGBB) is an FDA-approved, commercially available (AccuBoost®, Billerica, MA) mammography-based, breast brachytherapy system whereby the treatment applicators are centered on the planning target volume (PTV) to direct 192Ir emissions along orthogonal axes. This study evaluates the feasibility, implementation, and early results of NIIGBB for breast tumor bed boost in combination with external beam whole breast radiation therapy (WBRT), as part of post-lumpectomy radiation. Material and Methods: A privacy-encrypted online data registry was created to collect clinical and technical information from 8 independent academic and community-based institutions. Data were collected from consecutive 110 individual women with early stage breast cancer after breast conserving surgery, who received adjuvant WBRT (mean dose 48.3 ± 2.5 Gy) and tumor bed boost with NIIGBB between July, 2007 and March, 2010. Of the patients, 74% had invasive cancer, with 80% ER+ and 34% HER2+. NIIGBB was delivered before, during, or after WBRT in 57%, 39%, or 4% of the patients. Patient age and lumpectomy cavity size ranged from 32-88 yrs and 0.1-5.3 cm, respectively. Boost dose was delivered in 1.9 ± 0.3 Gy/fx for a total of 12.9 ± 3.4Gy. Toxicity and cosmesis were evaluated after radiation therapy and graded according to the Common Toxicity Criteria (v3.0) and the Harvard scale. Median follow up was 6 months (1-17 months). Results: Grade 1-2 skin toxicity was observed in 18%, 7%, and 0% during the acute (1-3wks), intermediate (4-26 wks), and late-intermediate (&amp;gt;26wks) periods. There were no Grade 3 or higher skin toxicity events. At 6 months, for the entire cohort, cosmetic grading was excellent, good, fair/poor in 52%, 48%, and 0%. The breast compression achieved for each treatment session was remarkably consistent with a mean mammographic plate separation of 6.4 ± 0.3 cm. Breast compression was scored as “uncomfortable” when NIIGBB was delivered before or during WBRT. The mean total duration of set-up and treatment per fraction was 16.7 ± 2.1 min. For each patient, the fraction-to-fraction variability in estimated PTV was low as 69% of treatments were completed with the same applicator size. Discussion: These data indicate that NIIGBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIIGBB is associated with acceptably mild normal tissue toxicity and favorable early cosmetic results. The application of NIIGBB before completion of WBRT may be associated with better patient tolerance at the expense of slightly less favorable short-term cosmetic outcome. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-13.