tbuckley/cabot-search huggingface dataset:
Abstract 18002: Coronary Collaterals Predict Improved Survival and Allograft Function in Patients with Coronary Allograft Vasculopathy
Authors: Kory J Lavine, Marc Sintek, Eric Novak, Susan Joseph, Gregory Ewald
Journal: Circulation (2011)

Coronary allograft vasculopathy (CAV) remains the most prevalent cause of allograft failure and cardiac mortality beyond the first year following heart transplantation. To date there are few proven therapies for this important disease. The presence of coronary collaterals has previously been demonstrated to impart a favorable prognosis in patients with ischemic heart disease. To determine whether the development of coronary collaterals is also associated with improved outcomes in patients with CAV, we performed a retrospective cohort study of all patients followed in the heart transplant clinic at Barnes Jewish Hospital between 1994 and 2008. The primary endpoint was the composite of all cause mortality, retransplantation, and inotrope dependence. LV end diastolic pressure and NYHA class served as surrogate measures of allograft function and heart failure symptoms. We screened 493 patients and identified 60 (13%) with moderate to severe CAV as defined by the International Society of Heart and Lung Transplantation. Coronary collaterals were present in 34 (57%) subjects. Patients with collaterals had a significantly lower risk of death, retransplanation, or inotrope dependence compared to patients without collaterals (OR 0.15, 95% CI 0.05-0.48, p= 0.002). In addition, patients with collaterals had lower LV end diastolic pressures and NYHA class. Multivariate analysis confirmed that the presence of collaterals independently predicted each of these outcomes. Immunohistochemical staining of biopsy specimens collected from patients with CAV revealed alterations in microvascular density that correlated with the presence of angiographically visible collaterals. Together these data demonstrate that the development of coronary collaterals predicts a favorable prognosis in patients with CAV and suggests that interventions aimed at promoting collateral growth may serve as effective therapies for this disease.
Ultrastructure of Rabbit Synovial Membrane
Authors: F. N. Ghadially, S. Roy
Journal: Annals of the Rheumatic Diseases (1966)

Recent electron microscopic studies of normal and pathological synovia have given a fresh insight into the structure and function of this tissue.The structure of human (Barland, Novikoff, and Hamer- man, 1962; Roy, Ghadially, and Crane, 1966) and guinea-pig synovium (Wyllie, More, and Haust, 1964) has been studied in some detail, but only brief accounts of normal rabbit synovium can be found in papers dealing with the removal of injected sub- stances from joints (Ball, Chapman, and Muirden, 1964; Cochrane, Davies, and Palfrey, 1965).The rabbit is the largest common laboratory rodent and as such its knee joint has been the subject of much study and many experimental procedures.It is therefore necessary to study and record the ultrastructure of the synovium of this valuable experimental animal in some detail.
Abstract 12585: Antianginal Efficacy of Ivabradine in Patients With History of Coronary Revascularization
Authors: Ioannis Zarifis, Violetta Grammatikou, Emmanouil Kallistratos, Apostolos Katsivas
Journal: Circulation (2014)

Introduction: Coronary revascularization procedures are widely performed for the symptomatic treatment of patients with coronary artery disease (CAD). Even after such procedures, angina symptoms often remain. Hypothesis: To evaluate the antianginal effectiveness and the effect on quality of life of ivabradine co-administered with a β-blocker, during 4-month therapy of CAD patients with a history of coronary revascularization. Methods: This is a post hoc analysis (926 post-revascularization patients) of a Pan-Hellenic, prospective, non interventional study including 2403 patients with CAD and stable angina. Data were recorded at baseline, and at 1 and 4 months after inclusion, while patients’ quality of life was assessed by means of the EQ-5D questionnaire. Results: Of 926 CAD patients who participated in the study, 28 (3%) prematurely discontinued treatment. Addition of ivabradine decreased mean heart rate from 80.3±9.5 bpm (1st visit) to 67.8±7.3 bpm (2nd visit) and 63.9±6.2 bpm (3rd visit) (P&lt;0.001). Mean number of angina attacks and nitroglycerin consumption decreased, respectively, from 2.2±2.3/1.5±2.2 times/week (1st visit) to 0.5±1.0/0.3±0.8 (2nd visit) and 0.3±0.6/0.1±0.4 times times/week (3rd visit) (P&lt;0.001). Moreover, the percentage of patients with angina CCS I (Canadian Cardiovascular Society classification) increased from 36% at baseline to 83% at study completion (P&lt;0.001), while those with angina CCS III-IV decreased from 21% to 2% (P&lt;0.001). All dimensions of the EQ-5D questionnaire were significantly improved after 4 months of treatment with ivabradine (P&lt;0.001) (Table 1). Compliance with ivabradine treatment was high. Throughout the trial, 884 patients (95.5%) were taking their treatment “every day” or “quite often.” Conclusions: These results confirm the antianginal effectiveness as well as the beneficial effect of ivabradine on the quality of life of patients with CAD and a history of coronary revascularization.
Antithrombins Wibble and Wobble (T85M/K): Archetypal Conformational Diseases With In Vivo Latent-Transition, Thrombosis, and Heparin Activation
Authors: N.J. Beauchamp, R.N. Pike, M. Daly, L. Butler, M. Makris, T.R. Dafforn, A. Zhou, H.L. Fitton, F.E. Preston, I.R. Peake, R.W. Carrell
Journal: Blood (1998)
Clopidogrel-Atorvastatin Interaction
Authors: Ryan A. Hobbs, Mohammad J. Tafreshi
Journal: Circulation (2004)

Clopidogrel-Atorvastatin InteractionTo the Editor:Clopidogrel is a pro-drug, which must be converted to its active form to exert its antiplatelet effect.This conversion appears to occur via the cytochrome P4503A4 isoenzyme. 1Several statins are substrates for CYP3A4, whereas others are not.As a result, some investigators have proposed that the coadministration of statins that are CYP3A4 substrates with clopidogrel may competitively inhibit the metabolic activation of clopidogrel in the liver in a dose-related manner. 2,3e read with interest the paper by Saw et al 4 evaluating the interaction between statins and clopidogrel from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial.Although similar event rates at 1 year comparing atorvastatin and pravastatin were reported, there appears to be a trend toward improved outcomes with pravastatin.In addition, event rates from day 29 to 1 year appear to be significantly higher with atorvastatin compared with pravastatin.This post hoc evaluation unfortunately was not adequately powered to assess event rates in the pravastatin group.Given these data and the in vivo data published by Lau et al 2 and more recently by Neubauer et al, 3 the potential for a significant interaction between clopidogrel and statins that are CYP3A4 substrates cannot be discounted.Because of limitations with post hoc and observational study evaluations of drug interactions, well-designed clinical trials are needed to specifically evaluate this interaction.
Abstract 17041: Attenuating the Interaction Between Delta PKC (dPKC) and the d Subunit of F1Fo ATP Synthase (dF1Fo) protects Against Myocardial Infarction in Rats
Authors: Matthew Walker, Robert W Caldwell, John A Johnson
Journal: Circulation (2014)

Our laboratory previously, developed a mitochondrially-targeted peptide inhibitor [NH2-YGRKKRRQRRRMLATRALSLIGKRAISTSVC-COOH] of the dPKC-dF1Fo interaction that improves contractility and energetics, and reduces infarction following ischemia / reperfusion (IR) injury in perfused rat hearts. In the present study we tested the hypothesis that dPKC inhibits ATP production in vivo via an interaction with dF1Fo to exacerbate cardiac IR injury. In rats administered the dPKC-dF1Fo inhibitor (5 ug/kg) intravenously (I.V.) for 20 min, we observed substantial FLAG immunoreactivity (The dPKC-dF1Fo inhibitor is tagged with a FLAG epitope) in cardiac subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria (n=6, p<0.03 and p<0.006). In rats receiving a 10 min coronary occlusion we observed a 5-fold induction of dPKC-dF1Fo co-immunoprecipitation (co-IP) in the left ventricular (LV) region at risk (RAR) for ischemia). This was reduced by 71 +/- 13 %,( p<0.001, n=8) in rats receiving the dPKC-dF1Fo inhibitor I.V. In add...
Abstract 5290: Cypher Long but not Short Isoform Specific Knockout Mice Result in Cardiac Signaling Defects and Dilated Cardiomyopathy
Authors: Hongqiang Cheng, Ming Zheng, Farah Sheikh, Kunfu Ouyang, Li Cui, Yusu Gu, Nancy Dalton, Ju Chen
Journal: Circulation (2008)

Our previous studies have demonstrated that Cypher, a PDZ-LIM protein localized at the Z line, plays a pivotal role in heart function. We recently identified long and short splice isoforms of Cypher, which are characterized by the presence and absence of LIM domains, respectively. The LIM domain of Cypher is thought to be involved in signaling, based on its ability to directly interact with signaling proteins. In human patients with dilated cardiomyopathy (DCM) we discovered Cypher gene mutations, which affect either long or short isoform or both isoforms. However, the precise molecular mechanisms underlying the role of Cypher isoforms in DCM remain unclear. To determine the role of Cypher isoforms in cardiac signaling and disease in vivo , we generated two Cypher isoform specific knockout mice. Selective ablation of Cypher long isoforms in mice resulted in partial neonatal lethality. However, hearts from viable Cypher long isoform deficient mice displayed Z line abnormalities and decreased cardiomyocyte widths, which resulted in a progressive form of DCM, characterized by fibrosis, calcification and lethality. The effects on cardiac function and disease observed in long-isoform specific Cypher knockout mice were preceded by significant decreases in cardiac protein kinase C and extracellular signal-regulated kinase signaling. These results are in contrast to Cypher short isoform deficient mice, which were viable with no overt cardiac morphology and signaling abnormalities. These results reveal distinct functional roles for Cypher isoforms in the heart as well as shed light into the molecular mechanisms underlying dilated cardiomyopathy.
Cataract surgery in very elderly patients
Authors: N. Beare, L. Dandona
Journal: BMJ (2001)

Editor—Wong's article on the effectiveness of cataract surgery in elderly people contains an emphasis on chronological age and final visual acuity as a measure of success.1 Wong does not mention the importance of biological age of individual patients and pays little attention to the potential improvement in daily functioning associated with cataract surgery. These are important factors when considering patients of any age for cataract surgery. But they are difficult to measure quantitatively and difficult to investigate; consequently they are not easily shoehorned into guidelines or health policy. A visual acuity of 6/12 or better is generally taken as a successful outcome in most studies in this area, and Wong applies this assumption to very elderly people. Very elderly people are, however, two to three times more likely to start with severely impaired vision (acuity of 6/60 or worse).2 Depending on an individual patient's circumstances, a final postoperative vision of 6/18 may still be a good result, with improvement in ability to perform activities of daily living.

The benefit risk analysis for cataract surgery varies for each patient. Wong cites work by Armbrecht et al,3 which has shown that elderly patients with moderate cataracts and mild age related maculopathy benefit more from cataract surgery than patients whose pathology is vice versa. This is common clinical sense and applied daily by ophthalmologists who are not familiar with this research. The importance of assessing the needs, risks, and potential benefits of cataract surgery on an individual patient basis means that guidelines are difficult to formulate. The decision on whether cataract surgery is appropriate depends on the clinical assessment by the examining surgeon, and discussion with the patient. Any ophthalmologists, or other healthcare professionals aspiring to do cataract surgery, must be prepared to use clinical acumen and take the responsibility for reaching the decision to operate themselves. Attempts to include chronological age as a factor in healthcare policy, or guidelines on management of cataract, are bound to founder.
Development and Evaluation of a Novel Patient Information System
Authors: Peter H Wise, Roger G Pietroni, Vikram B Bhatt, Catherine S Bond, Stephen Hirst, Richard J Hooker
Journal: Journal of the Royal Society of Medicine (1996)

A comprehensive patient information datafile of 320 topics has been developed, subserving the domains of medicine, surgery, gynaecology and paediatrics. The system was designed as loose-leaf sheets capable of being photocopied, as well as a computer-based datafile. In a four-practice study, 73% of consecutive general practice attenders could be issued with the relevant disorder or procedure information sheet. With a questionnaire return rate of 79%, 886 patients rated the three criteria of readability, understandability and usefulness of their leaflets as very or quite easy and very or quite useful in more than 94% of instances. This system could be a valuable adjunct to patient education in both general and hospital practice settings.
Abstract P229: Magnitude, Treatment, and Impact of Diabetes Mellitus in Patients Hospitalized with Non-ST Elevation Myocardial Infarction: A Community-based Study.
Authors: Hamza H Awad, Mayra Tisminetzky, Robert J Goldberg
Journal: Circulation (2014)

Background: Diabetes mellitus is a major risk factor for coronary heart disease (CHD) and CHD related mortality. Despite improvements in the medical management of patients presenting with non-ST segment elevation myocardial infarction (NSTEMI), this condition is still associated with a poor prognosis among diabetic patients. The objectives of this study in residents of a large central Massachusetts metropolitan area were to examine differences in the characteristics, treatment practices, and short-term outcomes of patients with and without a prior history of diabetes hospitalized for NSTEMI at all 11 medical centers in the Worcester, MA, metropolitan area. Methods: Data from the Worcester Heart Attack Study were analyzed for 4,366 patients diagnosed with NSTEMI during 6 biennial years between 1997 and 2009. Of these, 1,645 (38%) had previously diagnosed diabetes based on the review of information from hospital medical records. Results: Diabetic patients were more likely to be female, and to have a higher prevalence of several important comorbidities including hypertension (85 vs 67%), heart failure (42 vs 23%), stroke (19 vs 11%), and renal disease (32 vs 15%) compared with non-diabetics, respectively. While diabetic patients were significantly more likely to have been treated with ACE Inhibitors/ARBs (65 vs 53%), Calcium channel blockers (33 vs 26%), diuretics (72 vs 53%), and lipid lowering medications (66 vs 60%) during their index hospitalization, a similar proportion of diabetic and non-diabetic patients received aspirin and Beta Blockers. Diabetics were significantly less likely to have been treated with PCI (24% vs 29%), but were more likely to have undergone CABG surgery (7 vs 5%) than non-diabetics. Compared with non-diabetics, diabetic patients were more likely to have developed important in-hospital clinical complications including heart failure (50 vs 36%), stroke (2.0 vs 1.6%), cardiogenic shock (5 vs. 3%), and to have a longer hospital stay (6.7 vs 5.4 days). Diabetic NSTEMI patients were at significantly higher risk for dying during hospitalization compared with non-diabetics (12 vs 9%). Multivariable adjusted models showed significant declines in hospital death rates during the years under study for both diabetic and non-diabetic patients, though diabetic patients remained at greater risk for dying during each of the years under study. Conclusions: Our findings demonstrate that diabetic patients presenting with NSTEMI are more likely to suffer from comorbidities and remain at higher risk for developing complications or dying during hospitalization than non-diabetic patients presenting with NSTEMI at all central Massachusetts hospitals between 1997 and 2009.
Abstract 2092: FOXO1/Sprouty2 pathway regulates vascular tumor growth
Authors: Sriram Ayyaswamy, Wa Du, Christopher Anderson, Thuy L. Phung
Journal: Cancer Research (2015)

Abstract Vascular tumors are endothelial cell neoplasms with a wide spectrum of clinical presentations, ranging from benign infantile hemangiomas in children to low-grade malignant hemangioendotheliomas and highly aggressive angiosarcomas in adults. To date, the molecular basis of vascular tumor pathogenesis is poorly understood and standard therapy for these tumors have limited clinical efficacy. Forkhead box protein O1 (FOXO1) is a transcription factor with tumor suppressor function and is dysregulated in human cancer. In this study, we showed that FOXO1 suppressed vascular tumor growth, and mechanistically, the inhibitory effects of FOXO1 were mediated by Sprouty2. FOXO1 expression was reduced in a variety of human vascular tumors examined (infantile hemangioma, hemangioendothelioma and angiosarcoma) as compared with normal blood vessels as determined by western blotting and immunohistochemical stains. Knockdown of FOXO1 gene expression with short hairpin RNA resulted in increased vascular tumor cell migration and proliferation in vitro and in vivo. Conversely, over-expression of constitutively active FOXO1 in these cells suppressed cell growth. We observed that FOXO1 interacted with Sprouty2 promoter in situ in chromatin immunoprecipitation assay and increased Sprouty2 gene expression in tumor cells. Similar to FOXO1, Sprouty2 expression was reduced in vascular tumors. Over-expression of Sprouty2 decreased tumor cell growth and migration. Conversely, knockdown of Sprouty2 increased tumor growth in vitro and in vivo. Knockdown of Sprouty2 in cells with over-expression of constitutively active FOXO1 resulted in reduced tumor growth and “rescued” the FOXO1 phenotype, indicating that Sprouty2 is an important mediator of the biological effects of FOXO1. Microarray gene expression profiling of human angiosarcoma cells with Sprouty2 knockdown together with network data integration using bioinformatics analysis and validated by quantitative PCR revealed important Sprouty2-regulated genes that are involved in angiogenesis, apoptosis and growth signal transduction pathways, including the collagen gene family, Notch signaling pathway and the GTPase IMAP family members. In summary, these findings demonstrate important growth regulatory role of the FOXO1/Sprouty2 pathway in vascular tumors and highlight the potential roles of novel pathways downstream of Sprouty2 in these tumors. Citation Format: Sriram Ayyaswamy, Wa Du, Christopher Anderson, Thuy L. Phung. FOXO1/Sprouty2 pathway regulates vascular tumor growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2092. doi:10.1158/1538-7445.AM2015-2092
Abstract 5817.5: Assessment of Global Left Ventricular Function and Volumes with 320-Slice MSCT: A Comparison with 2D Echocardiography
Authors: Fleur R de Graaf, Joanne D Schuijf, Jacob M van Werkhoven, J Wouter Jukema, Gaetano Nucifora, Mark M Boogers, Arthur J Scholte, Albert de Roos, Ernst E van der Wall, Jeroen J Bax
Journal: Circulation (2008)

Background. Multi-slice computed tomography (MSCT) has been demonstrated as a feasible imaging modality for non-invasive assessment of coronary artery disease and left ventricular (LV) function analysis. Recently, 320-slice systems have become available with 16 cm anatomical coverage allowing prospective image acquisition of the entire heart within a single rotation or heart beat. However, limited data are currently available with these systems. The purpose of the present study therefore was to evaluate the accuracy of 320-slice MSCT in the assessment of global LV function as compared to 2-dimensional (2D) echocardiography. Methods. A head-to-head comparison between 320-slice MSCT and 2D echocardiography was performed in 40 patients (24 male; mean age 61 ± 9 years) with known or suspected coronary artery disease (CAD). During intravenous contrast agent administration, the entire heart was imaged in a single heartbeat, using prospective dose modulation (full dose during 65–85% of R-R interval). The following parameters were used: gantry rotation time 350 ms, tube voltage 120 kV, tube current 300–500mA. LV end-diastolic volumes (LVEDV) and LV end-systolic volumes (LVESV) were determined and the LV ejection fraction (LVEF) was derived. Two-dimensional echocardiography served as the gold standard. Results. Average LVEF was 59% ± 8% (range 31%–77%) as determined on 2D-echocardiography, compared with 61% ± 8% (range 33%–78%) on MSCT. Evaluation of LVEF by linear regression analysis showed a good correlation between MSCT and 2D-echocardiography (r = 0.84; p &lt; 0.001). A close correlation between MSCT and 2D-echocardiography was also demonstrated for the assessment of LVEDV (r = 0.81; p &lt; 0.001) and LVESV (r = 0.89; p &lt; 0.001). At Bland-Altman analysis, mean differences (± SD) of 20.88 ml ± 23.07 ml (p &lt; 0.01) and 6.83 ml ± 13.01 ml (p &lt; 0.01) were observed between MSCT and 2D-echocardiography for LVEDV and LVESV respectively. As a result, LVEF was slightly overestimated with MSCT (1.98% ± 4.54%; p &lt; 0.01). Conclusion. Accurate assessment of LV function and volumes is feasible with 320-slice MSCT in patients with known or suspected CAD.
Abstract 15227: Microrna-21 Contributes to Diabetic Cardiomyopathy Associated Cardiac Fibrosis
Authors: Akhilesh Kumar, Satish K. Raut, Uma Nahar Saikia, Rajni Sharma, Madhu Khullar
Journal: Circulation (2011)

Background: Myocardial fibrosis is most common pathological feature of Diabetic Cardiomyopathy (DCM) and is associated with differential expression of fibrogenic genes in diabetic heart. Several mi...
Dicoumarol
Authors: J. A. F. Roberts
Journal: BMJ (1948)

the reason for this peculiar phenomenon appears to be unknown.It seems, however, to be purely transitory.Lastly I think that, in the interests of the patients and for the sake of the reputation of the operation, fenestration ought only to be performed by surgeons already perfectly trained in aural surgery and with considerable experience of fenestration on the cadaver.It appears to me that professional ethics forbid the performance of this very specialized operation by surgeons who have not the necessary training.-Iam, etc.,