tbuckley/cabot-search huggingface dataset:
Abstract 2491: Neurohumoral Effects Of A New Oral Direct Renin Inhibitor In Stable Heart Failure: The Aliskiren Observation Of Heart Failure Treatment Study (ALOFT).
Authors: Bertram Pitt, John J McMurray, Roberto Latini, Aldo Maggioni, Scott D Solomon, Beverly A Smith, Christopher A Bush, Margaret F Prescott
Journal: Circulation (2007)

Background: Treatments that inhibit the renin-angiotensin-aldosterone system (RAAS) are of established benefit in heart failure (HF). These include ACE-inhibitor, angiotensin receptor blockers (ARB) and aldosterone antagonists (AA). In addition, beta blockers (BB) are also effective inhibitors of renin secretion. In this first placebo-controlled study, we have investigated whether the new orally-active direct renin inhibitor, aliskiren, has additional neurohumoral actions when added to these proven therapies. Methods: Inclusion criteria for the AL iskiren O bservation of Heart F ailure T reatment study (ALOFT) were: age 18 years or older, stable heart failure with NYHA functional class II–IV, prior or current hypertension, plasma B-type natriuretic peptide (BNP) concentration &gt;100 pg/mL and treatment with an ACE-I or ARB and BB, unless contraindicated or not tolerated. Patients were randomized to 3 months double-blind treatment with placebo or aliskiren (150 mg qd), added to standard therapy. Results: Overall, 302 patients (78% male, mean age 68 years, mean LVEF 31%) were randomized. Baseline treatment: 84% ACE-I, 15% ARB, 94% BB and 33% AA. Change in neurohormones versus baseline are shown in the table (expressed as % change using geometric means in an analysis of covariance model). Aliskiren significantly suppressed plasma renin activity (PRA), BNP and urinary aldosterone excretion overall and to a similar extent in patients treated and not treated with an AA. Conclusions: Aliskiren suppresses PRA in patients treated with a beta blocker and has additional and potentially beneficial neurohumoral effects in patients already comprehensively treated with neuroendocrine antagonists.
Interaction of Caffeine With Regadenoson-Induced Hyperemic Myocardial Blood Flow as Measured by Positron Emission Tomography
Authors: Oliver Gaemperli, Tiziano Schepis, Pascal Koepfli, Patrick T. Siegrist, Samuel Fleischman, Patricia Nguyen, Ann Olmsted, Whedy Wang, Hsiao Lieu, Philipp A. Kaufmann
Journal: Journal of the American College of Cardiology (2008)
SPECT in Adult Mosaic Downʼs Syndrome With Early Dementia
Authors: BASANT K. PURI, ZHIJIAN ZHANG, IQBAL SINGH
Journal: Clinical Nuclear Medicine (1994)

A 52-year-old patient with mosaic Down's syndrome exhibiting clinical features of early dementia who underwent high resolution SPECT neuroimaging is reported. While a CT scan of the brain showed no abnormality, cranial SPECT confirmed the presence of marked cortical blood flow deficits.
LV Outflow Tract Area in Discrete Subaortic Stenosis and Hypertrophic Obstructive Cardiomyopathy
Authors: Hirotsugu Mihara, Kentaro Shibayama, Kenji Harada, Javier Berdejo, Yuji Itabashi, Takahiro Shiota
Journal: JACC. Cardiovascular imaging (2014)
Abstract #3606: Azixa, a microtubule formation inhibitor in solid tumors: results of a phase 1 clinical trial
Authors: Apostolia Tsimberidou, Wallace Akerley, Chaan Ng, David Hong, Cynthia Uehara, Terri Warren, Margaret Yu, Edward Swabb, Razelle Kurzrock
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Purpose: Azixa\#8482; (MPC-6827) (4-arylaminoquinazolines) is a small molecule inhibitor of microtubule formation, which exerts its actions via binding to the same or nearby site as colchicine on \#946;-tubulin. We determined the dose-limiting toxicity (DLT) and maximum tolerated dose of Azixa\#8482; in patients with solid tumors. Experimental Design: Patients with advanced or metastatic cancer were treated with a 2-hour intravenous (IV) infusion once weekly for 3 consecutive weeks. Cycles were repeated every 28 days. The starting dose was escalated as follows: 0.3, 0.6, 1.0, 1.5, with subsequent increments of 0.6 mg/m² until the maximum tolerated dose 3.3 mg/m2 was reached. A conventional \#8220;3 + 3\#8221; design was used. Responses were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). Results: Forty-eight patients (median age, 56; median number of prior therapies, 4) with advanced solid tumors received therapy; and 93 cycles were administered (median 1; range, 1-10). Toxicities reported to be study drug-related include Grade 3 allergic reaction (n=1) and Grade 3 confusion (n=1) at 1.5 mg/m2, Grade 3 arrhythmia (n=1) at 3.3 mg/m2, and Grade 3 myocardial infarction at 3.9 mg/m2 (n=1) and 4.5 mg/m2 (n=1). Thirty-five patients (73%) reported no greater than Grade 1 drug-related toxicities. No drug-related DLTs were reported with azixa dose levels ranging from 0.3 to 3.3 mg/m2. Five (10.4 %) of the 48 patients achieved stable disease by RECIST for \#8805; 4 months (median = 5, range = 4-10). These patients had received 2 to 11 prior therapies and they had the following diagnoses: breast cancer, parathyroid cancer, carcinoid of the rectum, thymoma, and endometrial cancer. Conclusions : The maximum tolerated dose of Azixa\#8482; was determined to be 3.3 mg/m2 IV administered over 2 hours once weekly for 3 consecutive weeks every 4 weeks. Axiza therapy resulted in disease stabilization for \#8805; 4 months in 5 patients with heavily pretreated advanced cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3606.
Abstract 545: Polyethylene-glycol Coated Liposomal Adenosine Attenuates Hypotension and Bradycardia and Augments Cardioprotection Against Ischemia/reperfusion Injury in Rats - Nano-size Drug Delivery System Targeted to Infarcted Myocardium -
Authors: Hiroyuki Takahama, Tetsuo Minamino, Hiroshi Asanuma, Masashi Fujita, Masakatsu Wakeno, Masanori Asakura, Jiyoong Kim, Seiji Takashima, Kazuo Komamura, Masatsugu Hori, Naoki Mochizuki, Masafumi Kitakaze
Journal: Circulation (2007)

Background Liposome is a nano-size particle that can delay the drug degradation and induce the drug to the specific tissues including ischemia/reperfused myocardium. Coating liposome with polyethylene-glycol (PEG) prolongs the residence time in the blood stream. Although adenosine reduces myocardial infarct size in clinical trials, its half-time is extremely short and a high-dose of adenosine administration causes both hypotension and bradycardia. In this study, we investigated whether PEGylated liposomal adenosine minimizes systemic hemodynamic effects of adenosine and maximize cardioprotective effects against ischemia/reperfusion injury. Methods and Results We obtained PEGylated liposomal adenosine (average diameter: 126.2+/−42.9 nm) by the remote loading method. In rats, the intravenous administration of free adenosine (450 μg/kg/min for 10 minutes) decreased mean blood pressure and heart rate by 22.7% and 15.4% compared with the baseline, respectively. PEGylated liposomal adenosine at the same dose did not significantly change either mean blood pressure or heart rate compared with the baseline. Next, we produced myocardial infarction (MI) in male rats by 30-minutes of ligation of the left anterior descending coronary artery followed by reperfusion. We evaluated the accumulation of liposome in the hearts and infarct size 72 hours after the MI. Fluorescence microscopy revealed the accumulation of fluorescent-labeled PEGylated liposomes in ischemic, but not non-ischemic area. PEGylated liposomal adenosine (450 μg/kg/min), free adenosine (450 μg/kg/min) or free-PEGylated liposome was intravenously administered for 10 minutes starting 5 minutes before the onset of reperfusion. PEGylated liposomal adenosine significantly (p&lt;0.05 each) reduced infarct size (11.4±3.1 %) compared with free adenosine (21.7±3.0%) or free PEGylated liposome (23.6±2.2%). Conculusion PEGylated liposomal adenosine attenuated the systemic hemodynamic effects of adenosine and augmented cardioprotection against ischemia/repefusion injury. Nano-size PEGylated liposomal adenosine is a promising candidate for the adjunctive therapy for AMI.
Abstract 15085: Long-Term Outcomes of Patients With Coronary Artery Disease and Type 2 Diabetes Mellitus With Chronic Kidney Disease Undergoing Surgery, Angioplasty, or Medical Treatment
Authors: Eduardo G Lima, Cibele L Garzillo, Paulo C Rezende, Rodrigo M Melo, Thiago Scudeler, Luiz A Cesar, Alexandre C Hueb, Whady Hueb, Jose A Ramires, Roberto Kalil Filho
Journal: Circulation (2013)

Background: Diabetes (DM) is related to worse prognosis in coronary artery disease (CAD) patients. There is an additional risk when chronic kidney disease (CKD) is present. Few data are available c...
Abstract 2322: Genetic Risk for Low HDL-cholesterol or High LDL-cholesterol Concentrations
Authors: Mitsutoshi Oguri, Kimihiko Kato, Tetsuro Yoshida, Takeshi Hibino, Kazuhiro Yajima, Tetsuo Fujimaki, Kiyoshi Yokoi, Hitoshi Matsuo, Shunichiro Warita, Tomonori Segawa, Sachiro Watanabe, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa, Sahoko Ichihara, Yoshiji Yamada
Journal: Circulation (2007)

Introduction. A low serum concentration of HDL-cholesterol and a high serum concentration of LDL-cholesterol are risk factors for atherosclerosis. Our goal was to identify genetic variants that confer susceptibility to a low serum concentration of HDL-cholesterol (&lt;1.04 mmol/L) or a high serum concentration of LDL-cholesterol (≥3.64 mmol/L). Methods. A total of 5213 individuals from two independent populations was examined: Subject panel A comprised 3794 individuals who either visited outpatient clinics of or were admitted to the participating hospitals because of various symptoms or for a health checkup; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. Given the multiple comparisons of genotypes with these conditions, we adopted the criterion of a false discovery rate (FDR) of &lt;0.05 for significant association in initial screening with the chi-square test. Results. Examination of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that six [−1131T→C, −3A→G, and 553G→T (Gly185Cys) of APOA5 ; −250G→A and −515C→T of LIPC ; 13989A→G (Ile119Val) of CYP3A4 ] and three [4070C→T (Arg158Cys) and 3932T→C (Cys112Arg) of APOE ; 190G→A (Val64Ile) of CCR2 ] polymorphisms were significantly (FDR &lt; 0.05) associated with low HDL-cholesterol and high LDL-cholesterol, respectively, in subject panel A. To validate these associations, we examined the same polymorphisms in subject panel B. The three polymorphisms of APOA5 and two polymorphisms of APOE were significantly associated with low HDL-cholesterol and high LDL-cholesterol, respectively. The serum concentrations of HDL-cholesterol and LDL-cholesterol differed significantly ( P &lt; 0.01, ANOVA) among genotypes of the corresponding polymorphisms in both subject panels. The polymorphisms of APOA5 and APOE were each in linkage disequilibrium. Conclusions. Polymorphisms of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively. Genotyping of these polymorphisms may prove informative for prediction of the genetic risk for these conditions.
Impaired Myocardial Oxygenation Response During Stress in Patients With Severe Aortic Stenosis: Insights From Oxygenation-sensitive Cardiovascular Magnetic Resonance
Authors: M Mahmod, J M Francis, N Pal, A Lewis, D Sairia, R De Silva, M Petrou, R Sayeed, S Westaby, H Ashrafian, S Neubauer, T D Karamitsos
Journal: Circulation (2013)
Abstract 19340: Long-term Clopidogrel Therapy and The Impact on CV Mortality: Lessons from the Large Randomized Controlled Trials
Authors: Freek W Verheugt, Jeroen Jaspers Focks, Marc A Brouwer
Journal: Circulation (2010)

Objective: Long-term clopidogrel treatment has become standard of care for ACS patients treated with or without coronary intervention. Also for other indications, clopidogrel has been studied. Conc...
Abstract 368: Beta-1 Adrenergic Receptor Haplotypes Based on Codon 389 and 49 Polymorphisms Influence the Magnitude of the Left Ventricular Ejection Fraction Response to Beta-blocker Therapy
Authors: Ronald Zolty, Brian D Horne, Mona Cantu, JoAnn Lindenfeld, Simon Shakar, Eugene E Wolfel, Andreas Brieke, Joshua A Melcer, Brian D Lowes, Michael R Bristow
Journal: Circulation (2007)

Introduction  Long term stimulation of the sympathetic nervous system is associated with myocardial remodeling and randomized trials have demonstrated β-blockers improve mortality and left ventricular ejection fraction (LVEF) in the HF population. Improvement of the LVEF with β-blocker therapy displays a high degree of inter-individual and inter-ethnic variation that might be explained by underlying genetic variation in adrenergic mechanisms. The β 1  adrenergic receptor (AR) plays a critical role for maintenance of homeostasis in the human heart. β 1  389 and 49 AR polymorphisms have been shown to act as disease modifiers in HF. A haplotype represents a certain combination of two or more polymorphism at a locus. Haplotypes are often more informative in association studies than are individual single nucleotide polymorphisms (SNPs). We hypothesized that the inter-individual variation in LVEF with β-blockers might be influenced by the different haplotypes of the β 1  AR gene   Methods.  485 patients with LVEF ≤ 40% from any etiology were selected from the HF Clinic at the University of Colorado Hospital and correlation between the different β-1 AR haplotypes and LVEF response to β-blockade therapy was evaluated retrospectively.   Results  With β 1  AR 389 and 49 SNP, haplotype analysis demonstrated that for African Americans, the combination Gly389/Gly49 did not co-occur. There was a highly significant relationship between these 4 genetic combinations and LVEF improvement.The association between the different haplotypes and LVEF changes on β-blockade therapy are shown in Table with the  P -values in parentheses. A  P -value 389 /Ser 49  wild-type haplotype. Conclusion This study shows a strong and significant association between the different β-1 AR haplotypes (based on codon 49 and 389 polymorphisms) and improvement in LVEF with β-blocker therapy.
Abstract #2486: TRMT12 overexpression in cancer cells affects the cell cycle and the nonsense mediated decay pathways by regulating the SMG-1 kinase, a member of the PIKK family of kinases
Authors: Virginia Rodriguez, Bradley Carlson, Akiko Noma, Abdel Elkahloun, Jeffrey Green, Tsutomu Suzuki, Settara Chandrasekharappa
Journal: Cancer Research (2009)

Previously, we reported the overexpression of TRMT12 (tRNA methyltransferase 12) in breast cancer. This gene is located on chromosome 8 in the 8q24 region, an area commonly amplified in many types of cancer. The human TRMT12 gene has never been studied. TRMT12 is homologous to the yeast TYW2, a tRNA methyltransferase involved in the posttranscriptional modification that converts guanosine to wybutosine, a highly modified base in tRNA-phenylalanine. Wybutosine is present only in tRNA-phenylalanine at the 37th position adjacent to the anticodon. This modification stabilizes the codon-anticodon interaction and functions to maintain the correct reading frame. Recently, we cloned the human TRMT12 gene and determined that TRMT12 catalyzes the third step in the biosynthetic pathway of wybutosine. This is the first time the biological function of one of the human enzymes in the wybutosine pathway has been demonstrated. We find that wybutosine modification in tRNA-phenylalanine is not affected in a mouse mammary tumor model that overexpresses Trmt12. To determine the effect of TRMT12 overexpression in cancer, we evaluated the expression changes in cells treated with TRMT12 siRNAs. Results indicate that the SMG-1 gene had a >2 fold increase in expression when TRMT12 was brought down, and this was validated by RT-qPCR and Western blot analysis. SMG-1 is a critical phosphatidylinositol-3-kinase-related kinase (PIKK) that is a key player in DNA damage response and in the nonsense mediated decay pathway (NMD), a surveillance system that maintains the quality and fidelity of mRNA transcripts. Overexpression of TRMT12 results in altered expression of SMG-1, a reduction in p53 (Ser 15) phosphorylation and associated disruption to the cell cycle; overexpression of TRMT12 also results in compromising the NMD pathway. Thus, overexpression of TRMT12 in cancer is likely to disrupt SMG-1 function, which in turn may allow DNA damage to go unchecked and mutated RNA transcripts to escape degradation.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2486.
Abstract 6207: Derivation of a Novel Prediction Algorithm for Idiopathic Venous Thromboembolism in Women
Authors: Brendan M Everett, Nina P Paynter, Julie E Buring, Robert J Glynn, Nancy R Cook, Paul M Ridker
Journal: Circulation (2008)

Background : Established risk factors for idiopathic venous thromboembolism (VTE) include age, prothrombotic mutations, and obesity. A risk prediction algorithm might allow clinicians to focus preventive efforts. Methods : We derived a prediction model for idiopathic VTE using 22 possible predictor variables and their interactions in 19,458 initially healthy Caucasian women who were followed for incident idiopathic VTE. Minimization of the Bayes Information Criterion (BIC) was used to help identify the best, most parsimonious model, and estimates of discrimination (C-index) and calibration (Hosmer-Lemeshow (H-L) statistic) comparing observed and predicted risk were computed and compared with a model including only age and weight. Results: The mean (SD) age was 54.1 (7.1) years, the mean (SD) weight 69.9 (14.1) kilograms, and 2.8% and 5.3% of participants carried the prothrombin and factor V Leiden mutations, respectively. After a median of 12.4 years of follow up, we observed 130 idiopathic cases of VTE. The best fitting model included log(age), log(weight), log(apolipoprotein A1), and the presence of the prothrombin or factor V Leiden mutations (C-index 0.704; H-L statistic 5.9). When compared to model including only log(age) and log(weight) (C-index 0.636; H-L statistic 3.9), the full model achieved higher discrimination at similar calibration and led to a net reclassification of 34.5 percent (6705) of participants, all correctly. Conculsion: In our population of middle-aged, initially healthy Caucasian women, a model that includes age, weight, apolipoprotein A1, and the prothrombin and factor V Leiden mutations predicts incident idiopathic VTE more accurately than one including age and weight alone. Table. Idiopathic venous thromboembolism risk reclassification - basic and best-fitting models
Abstract 4155: Comparison of Stent Underexpansion and Recoil Between 4 Commercially Available First- and Second-generation Coronary Stents
Authors: Byung-Ok Kim, Jeong Hoon Kim, Choong Won Goh, Young Sub Byun, Kun-Joo Rhee
Journal: Circulation (2009)

Background: Failure to achieve predicted stent diameter caused by stent underexpansion and stent recoil poses a risk of treatment failure in coronary stenting. Due to improved stent design and deli...
P1205 : Comprehensive analyses of autoimmune hepatitis type 1 associated mRNA, lncRNA, and miRNA in CD4+ T cells targeted by prednisolone treatment
Authors: R. Nakagawa, R. Muroyama, S. Ito, K. Takano, K. Goto, M. Nakano, C. Saeki, Y. Matsubara, N. Kato, M. Zeniya
Journal: Journal of Hepatology (2015)
Controversies in Management: Should backache be treated with spinal fusion?
Authors: J. P O'Brien
Journal: BMJ (1996)

Backache indicates pain originating in the vertebral column (most commonly in the lowest two mobile segments of the lumbar spine). It is felt mainly in the lower back and buttocks, often being referred to the lower limbs. Referred pain in the limb can be confused with radicular pain (sciatica) from nerve root compression.

Fusion is a non-specific term. It comes from the Latin fundere—to pour or to melt. In the context of the spine, fusion entails welding or stiffening two or more vertebral bodies. Arthrodesis might therefore be a more appropriate word (removing of the articular surfaces and securing bony union1).

Hippocrates in 380 BC observed spontaneous fusion of the facet joints in a case of spinal tuberculosis. It was nature's attempt to halt the progress of the deformity. Hibbs read the work of Hippocrates, and in 1911 surgically fused the posterior spinal elements in young patients with spinal tuberculosis.2 This successfully prevented subsequent deformity. Later Hodgson and Stock …
Reduction of tumor growth and spontaneous metastasis through induction of carbohydrate cross-reactive apoptotic antibodies
Authors: Behjatolah Monzavi Karbassi, Cecile Artaud, Fariba Jousheghany, Jaime Carcel-Trullols, Leah Hennings, Soheila Korourian, Thomas Kieber-Emmons
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4275 

Induction of immune responses against metastatic disease is the most challenging strategy in cancer vaccine development. Tumor cells, however, escape an ongoing immune response using various mechanisms including loss of target antigen and down regulation of MHC molecules or disruption of complement cascade. Therefore, employing novel anti-tumor immunological mechanisms in the immunotherapy array are needed. Induction of humoral responses that mediate apoptosis is perceived to be beneficial in vaccine formulations. Some plant lectins like Griffonia simplicifolia lectin I (GS-I) and wheat germ agglutinin (WGA) mediate apoptosis of tumor cells. We hypothesize that using these lectins as a template to select peptide mimotopes enables us to develop mimotope vaccines capable of inducing carbohydrate cross-reactive apoptotic antibodies upon immunization. We selected a peptide mimotope based on its specific reactivity with the above-mentioned lectins. Immunization of animals with the selected mimotope induced serum IgM antibodies that bound to murine 4T1 and human MCF7 cell lines as assayed by flow cytometry. Serum antibodies mediated apoptosis in both cell lines as assayed by annexin V surface expression, paralleling the apoptotic activity of the lectins. Confocal microscopy demonstrated that serum IgM antibodies internalized after co-incubation with the cells. Using 4T1 as a spontaneous metastatic tumor model, we observed that immunization of tumor-bearing animals with the mimotope significantly increased the survival time that was attributed to an observed diminished metastatic ratio of the tumor cells colonizing the liver. In prophylactic immunization of naive mice, we found that the vaccine is able to also affect solid tumor and lung metastasis. This finding parallels suggestions that carbohydrate reactive IgM can function as apoptotic mediators of tumor cell. Therefore, induction of apoptotic IgM antibodies might be targeted as an end-point in the development of vaccination strategies against cancer especially in the adjuvant setting for metastatic disease.