tbuckley/cabot-search huggingface dataset:
Abstract P306: Effect of A Low-Carbohydrate Diet on Weight and Cardiovascular Risk Factors: A Randomized Controlled Trial
Authors: Lydia A Bazzano, Kristi Reynolds, Tian Hu, Lu Yao, Calynn Bunol, Yanxi Liu, Chung-Shiuan Chen, Jiang He
Journal: Circulation (2012)

There are few studies examining the effects of a diet low in carbohydrates on cardiovascular disease (CVD) risk factors in the long term, particularly in contrast to the current dietary recommendations for decreased fat intake to reduce risk of CVD. We recruited 148 study participants with a body mass index (BMI) of 30–45 kg/m2, who were free of diabetes, CVD and kidney disease at baseline and randomly assigned them (74 in each group) to either a low carbohydrate diet (&lt;40 g/day) or a low fat (&lt;30% energy from fat, &lt;10% from saturated fat) diet. Participants met with a study dietitian weekly for the first month then in group settings bi-weekly for 5 months then monthly for the next 6 months. Each group was provided the same behavioral curriculum related to diet emphasizing portion control and eating habits. Two 24-hour dietary recalls were conducted at each clinic visit (0, 3, 6 and 12 months of intervention). The primary outcome measures were weight, body composition, lipids, blood pressure, and glucose. Mean age of participants was 46.8 years, mean BMI was 35.4 kg/m2; 11.5% were men, and 51% were African-American. Of the study participants, 60 in the low fat group (81.1%) and 59 in the low carbohydrate group (79.7%) completed the entire intervention. At 12 months, mean total energy intake on the low carbohydrate diet was 1,448 kcal/day with 23.6% from protein, 40.7% from fats, and 34.0% from carbohydrate versus 1,527 kcal/day with 18.6% from protein, 29.8% from fats, and 50.0% from carbohydrate on the low fat diet. Compared to low fat diets, over 12 months the low carbohydrate group had greater reductions in weight (net change −3.62 kg, p&lt;0.001), fat mass (−2.83 kg, p&lt;0.0001), waist circumference (−1.79 cm, p=0.03), triglycerides (−12.83 mg/dL, p=0.05), and a greater increase in high density lipoprotein cholesterol (HDL-C, 6.74 mg/dL, p&lt;0.001). There were no differences in net changes between diets for total cholesterol, low density lipoprotein cholesterol, blood pressure, glucose, creatinine, or lean body mass. Our findings document that a low carbohydrate diet was more effective for weight loss than a low fat diet, and did not have significant adverse effects on cardiovascular risk factors. In contrast, the low carbohydrate diet improved HDL-C and triglycerides as compared to a low fat diet. Restricting carbohydrates is an effective method of weight loss and could be recommended for persons with and without increased CVD risk factors who need to lose weight.
Abstract 5664: Left Atrial Strain In Patients With Atrial Fibrillation: Relationship To Fibrosis By Delayed Enhancement-MRI
Authors: Suman S Kuppahally, Robert S Oakes, Eric N Fish, Eugene Kholmovski, Sathya Vijayakumar, Edward V DiBella, Rob S MacLeod, Sheldon E Litwin, Nassir F Marrouche
Journal: Circulation (2008)

Introduction: The extent of left atrial (LA) wall fibrosis detected by delayed enhancement (DE)-cardiac MRI prior to catheter ablation of atrial fibrillation (AF) appears to predict procedural success. However, it is currently unknown how the degree of fibrosis affects atrial mechanical function. Methods: Prior to catheter ablation of AF, 31 patients underwent DE-CMRI and 2-dimensional transthoracic echocardiography. 3D segmentation of LA was performed and the degree of fibrosis was determined using a semi-automated quantification algorithm. Longitudinal mid-septal and mid-lateral LA wall velocity, strain and strain rate were measured during ventricular systole from the apical 4-chamber view by velocity vector imaging. Results : There was greater percent of fibrosis as LA maximum (R = 0.4, p = 0.05) and minimum (R=0.52, p = 0.008) volumes increased. Figure shows examples of DE-CMRI and strain curves (C) for two patients: Patient 1(A) with mild fibrosis and patient 2 (B) with extensive fibrosis. Patient 1 shows much larger strain than patient 2. Larger LA volumes correlated inversely with maximal LA mid-lateral systolic wall strain (p &lt; 0.005). The percent fibrosis also correlated inversely with maximal LA mid-lateral systolic wall strain (R=0.56, p &lt; 0.005) and the systolic strain rate (R = 0.58, p = 0.002). Conclusion: LA strain and strain rate can be assessed using standard echocardiographic gray scale images. LA strain is related to both atrial volumes and fibrosis, which are markers of atrial disease progression. This relationship may represent changes in the properties of LA substrate. These novel imaging approaches may be helpful in predicting outcomes in patients with AF.
Abstract 12821: Short Interfering RNA-Mediated Knockdown Of Glucose-6-Phosphate Dehydrogenase Impairs Cardiac Contractile Performance and Efficiency in Conscious Dogs
Authors: Claudio Vimercati, Khaled Qanud, Rakhee Gupte, Neel Patel, Rahim Khan, Michael Pfeffer, Margherita Maioli, Eugene Cioffi, Sachin Gupte, Fabio A Recchia
Journal: Circulation (2011)

The oxidative pentose phosphate pathway (oxPPP) generates cytosolic NADPH and has been found critically important for redox homeostasis and function of isolated cardiomyocytes. However, no studies ...
Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data
Authors: Hiroshi Deguchi, Yajnavalka Banerjee, Sunia Trauger, Gary Siuzdak, Ewa Kalisiak, José A. Fernández, Linh Hoang, Minerva Tran, Subramanian Yegneswaran, Darlene J. Elias, John H. Griffin
Journal: Blood (2015)
Targeted downregulation of TGF-beta2 as immunotherapy for high-grade glioma: A phase IIb study
Authors: P. Hau, M. Kunst, J. Pichler, V. E. Parfenov, K. V. R. Sastry, L. Spitznagel, M. Zaaroor, U. Bogdahn, K.-H. Schlingensiepen
Journal: Journal of Clinical Oncology (2005)

1537 Background: High-grade (malignant) glioma are highly aggressive tumors showing marked overexpression of transforming growth factor-beta2 (TGF-beta2). TGF-beta plays a key role in malignant progression by inducing proliferation, invasion and metastasis, angiogenesis and immunosuppression and is responsible for the immunodeficient state of malignant glioma patients. AP 12009, a phosphorothioate antisense oligodeoxynucleotide specific for the human TGF-beta2 mRNA, has been developed as a targeted anti-tumor therapy. AP 12009 has already proven safety and shown anti-tumor activity in phase I/II clinical studies as therapy for recurrent high-grade glioma after intratumoral infusion. Methods: Based on the successful phase I/II studies with AP 12009 a phase IIb multinational study in adult patients with recurrent high-grade glioma, i.e. Anaplastic Astrocytoma (AA), WHO grade III, and Glioblastoma Multiforme (GBM), WHO grade IV, is currently ongoing. Patients are randomized into 3 treatment groups to receive either one of two doses of AP 12009 or standard chemotherapy, i.e. temozolomide, or the combination Procarbazine/CCNU/Vincristine (PCV). The primary objectives of this open label, phase IIb study are response rate (RR), progression free survival (PFS) and overall survival at different time points. AP 12009 is administered intratumorally as continuous high-flow microperfusion for 7 days every other week for up to 11 cycles. Both, efficacy and safety will be used as criteria for evaluation. Results and Conclusion: In the previous phase I/II studies the median overall survival time was longer than the one reported in the recent literature (Yung et al, 2000, Theodosopoulus et al, 2001, Chang et al, 2004) on standard chemotherapy. Data on anti-tumor activity in phase I/II studies with 24 patients included several patients with stabilizations and two patients with complete tumor remissions, both of them long-lasting without recurrence. In the current phase IIb study more than 120 patients have been enrolled. Based on the clinical data in malignant glioma and very encouraging preclinical results in pancreatic carcinoma AP 12009 is now in phase I/II studies in pancreatic carcinoma as its second tumor indication. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisense Pharma GmbH Antisense Pharma GmbH Antisense Pharma, Antisense Pharma GmbH
The IL-12Rβ2 gene functions as a tumor suppressor in human B cell malignancies
Authors: Irma Airoldi, Emma Di Carlo, Barbara Banelli, Lidia Moserle, Claudia Cocco, Annalisa Pezzolo, Carlo Sorrentino, Edoardo Rossi, Massimo Romani, Alberto Amadori, Vito Pistoia
Journal: Journal of Clinical Investigation (2014)

It has come to our attention that multiple gel images in Figure 1A were inappropriately duplicated from a previous
Abstract 3307: Early Use of Beta-blockers Attenuates Systemic Inflammatory Response and Lung Oxygenation Impairment after Distal Type Acute Aortic Dissection
Authors: Yusuke Jo, Toshihisa Anzai, Yasuo Sugano, Hidehiro Kaneko, Kotaro Naito, Koji Ueno, Takashi Kohno, Toshiyuki Takahashi, Tsutomu Yoshikawa, Satoshi Ogawa
Journal: Circulation (2007)

BACKGROUND: Systemic activation of the inflammatory system after aortic injury may play a role in the development of lung oxygenation impairment (LOI) in patients with acute aortic dissection (AAD). We have reported that serum C-reactive protein (CRP) elevation is an independent predictor of this complication. We evaluated the effect of beta-blocker on systemic inflammation and the development of LOI after distal type AAD. METHODS: A total of 49 patients, who were admitted with distal type AAD and treated conservatively, were examined. Patients were divided into 2 groups according to the presence or absence of beta-blocker treatment, started within 24 hours of the onset. White blood cell (WBC) count, serum CRP level and arterial blood gases were measured serially. Clinical outcome, maximum WBC count, maximum CRP level, and lowest PaO 2 /FiO 2 (P/F) ratio were compared between the two groups. RESULTS: There was no difference between the groups in patients’ backgrounds, blood pressure, serum level of CRP, WBC count and P/F ratio on admission. Beta-blocker treatment was associated with lower maximum WBC count (14,856 ± 3201 vs. 11,687 ± 2610 /mm 3 , p =0.0028) and lower maximum serum CRP level (28.2 ± 20.5 vs. 14.2 ± 5.6 mg/dl, p =0.0004). The minimum P/F ratio was higher in patients with beta-blocker than in those without (140 ± 41 vs. 226 ± 90 mmHg, p =0.0076). Multivariate analysis revealed that administration of a beta-blocker was an independent negative determinant of LOI (P/F ratio ≤ 200 mmHg). CONCLUSIONS: Early use of beta-blockers prevented excessive inflammation and LOI after distal type AAD, suggesting a pleiotropic effect of beta-blockers on the inflammatory response after AAD.
Lord Todd of Trumpington and Lord Zuckerman of Burnham Thorpe
Authors: John Warden
Journal: BMJ (1989)

Labour party's view of complaintsThe NHS complaints procedure needs over- hauling, says the Labour party, because it is too complex, is inflexible, encourages con- frontation, and too frequently fails to give a simple explanation and apology.Information on complaints is not collected centrally so the party decided to collect its own statistics by writing to district health authorities and family practitioner commit- tees (FPCs) in England.The results are given in a new report, When Things Go Wrong.Compensation and Complaints in the NHS.In it the Labour party adds its voice to those, including the BMA, who are calling on the government to-introduce no fault com- pensation so that victims ofmedical accidents get adequate and prompt compensation without having to face lengthy court actions.The party plans to seek an amendment to the National Health Service and Community Care Bill when it reaches the committee stage.
Abstract 12697: Omega-3 Fatty Acids Effects on Carotid IMT in Metabolic Syndrome
Authors: Edward A Gill, Michael A Chen, Pathmaja Paramsothy, Brian Fish, Daniel Isquith, Aarthi Thirumalai, Xue-Qiao Zhao
Journal: Circulation (2014)

Background:  37% of Americans are affected by metabolic syndrome (MS), but the effect of Omega-3 fatty acids (O3FA) in MS is largely unexplored. By new guidelines, those with MS may not meet criteria for statin treatment but are still at increased risk of CVD. O3FA supplementation reduced CV events in 2 large trials (Gissi-Prevenzione and JELIS). In a prior abstract we reported the impact of O3FA on lipid levels and inflammatory markers in 101 subjects with MS. Apo B, Apo A1, and triglycerides were significantly reduced, but there was no change in CRP or serum amyloid A. Here we report results on CIMT.   Methods:  101 subjects with MS, mean age 55.1 years, 53% women, were randomized to placebo or O3FA (1.8 grams of EPA +DHA) daily vs. matching placebo for 2 years. Common carotid (CCIMT) and internal carotid IMT (ICIMT) were measured at baseline and at 2 years.   Results:  80 subjects completed the CIMT protocol. There were no significant differences in any baseline clinical characteristics between groups (supplement (S) vs. placebo (P)), or between baseline mean CCIMT or ICIMT. After two years, there were non-significant increases in the IMT in both S and P but no between group differences (see table and figure). The results were similar whether comparing the average of the maximum of both sides or comparing the sides with the greatest IMT at baseline. Removing the significant outlier in the S group, did not change the results (see figure).   Conclusion:  In this modest sized sample group, despite favorable effects on lipid levels, treatment with O3FA did not stop progression of carotid IMT although the increase in CIMT in both groups was small and insignificant.
Abstract 3649: Menstrual Cycling and Mechanisms of Cardiovascular Disease Events in Post-Menopausal Women: Results from the NIH-NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Authors: B. Delia Johnson, C. Noel Bairey Merz, Ricardo Azziz, Glenn D Braunstein, Leslee J Shaw, Carl J Pepine, George Sopko, Sheryl F Kelsey
Journal: Circulation (2007)

Background: Menstrual cycling irregularity is being associated with greater frequency of diabetes and adverse cardiovascular (CV) events, suggesting a mechanistic link between ovarian dysfunction, CAD risk factors, and CAD. Confirmation of this link and potential explanatory mechanism(s) have not been established. Methods: We compared 686 postmenopausal women with and without a history of irregular cycles who were undergoing coronary angiography for suspected ischemia and enrolled in the WISE study. Coronary angiography was assessed by a core laboratory, and the women were prospectively followed for a median of 5.9 years. Chi square and rank sums analyses were used to compare the women on the presence and severity of CAD, CAD risk factors, and CV events. Multivariate Cox regression, adjusting for angiographic CAD and CAD risk factors was used to define time to death, MI, stroke, and angina hospitalization. Results: Overall mean age was 62, 18% were non-white, 130 (19%) reported a history of irregular cycles, and 42% had CAD (≥ 50% stenosis). Women with irregular cycles were younger (p=0.01) but did not exhibit more diabetes, obesity, or metabolic syndrome than those with regular cycles. They became menopausal at a younger age (42 ±10 vs 46 ±8, p=0.001) and had more frequent hysterectomy or oophorectomy (both p&lt;0.01). Women with irregular cycles had a similar adjusted prevalence and severity of angiographic CAD compared to those without irregular cycles, yet had a doubled risk for MI (6% vs. 3%, p=0.02) and higher angina hospitalization rate (34% vs. 28%, p=0.01). No differences were found for the incidence of stroke or death. The relationship was maintained in risk-adjusted models controlling for metabolic syndrome, ethnicity and angiographic CAD severity (p=0.01 for MI and p=0.01 for angina hospitalization). Conclusion: Although less commonly applied, a history of menstrual cycling irregularity may be an important clinical marker of downstream risk, which is not immediately explained by the presence or severity of CAD risk factors or angiographic CAD. Additional, non-CAD risk factors, such as hormonal, inflammatory and thrombotic variables, may play a role mechanistically in the link between menstrual irregularity and adverse events.
Abstract 41: Signal Characteristics of 2-d Epicardial Surface and Lead-II ECG During Untreated Ventricular Fibrillation and Cardiopulmonary Bypass Resuscitation
Authors: David D Salcido, Greggory J Housler, Eric S Logue, Youngmin Kim, James J Menegazzi
Journal: Circulation (2010)

Background: Quantitative waveform measures (QWM) of the ventricular fibrillation (VF) electrocardiogram (ECG) are descriptors of electrical activity of the heart during VF. The correspondence betwe...
Abstract 16897: Morphologic and Functional Assessment of Coronary Artery Disease: Potential Application of CT Angiography and Myocardial Perfusion Imaging
Authors: Sadako Motoyama, Masayoshi Sarai, Kaori Inoue, Hideki Kawai, Hiroto Harigaya, Hajime Ito, Kayoko Takada, Hiroyuki Naruse, Junichi Ishii, Jagat Narula, Yukio Ozaki
Journal: Circulation (2011)

Purpose: Now that the technological advances have substantially and favorably allowed reduction in radiation burden both from CT angiography (CTA) and myocardial perfusion imaging (MPI) by single-photon emission computed tomography (SPECT), and because CT-SPECT combination is becoming a mainstream investigative tool, we evaluated the role of combined evaluation of MPI and CTA in coronary artery disease (CAD). For CTA, we evaluated both, the extent of luminal stenosis as also the features of high-risk plaques (HRP, including positive remodeling and low attenuation. Methods: 280 patients (65±11 years, mean f/u: 26 months) underwent both CTA and MPI. Patients without significant stenosis on CTA, or suspected of stenosis by CTA but normal MPI findings were classified as normal, and patients with significant CTA stenosis and reversible defect on MPI were classified as abnormal. On CTA, HRP was also reported regardless of luminal stenosis. Patients were classified into group 1: abnormal CTA and MPI (n=81), group 2: normal CTA and MPI but with HRP (n=25), and group 3: normal by CTA and MPI and also no HRP (n=174). Cardiac events were defined as percutaneous coronary intervention (PCI) or bypass surgery (CABG) after CTA and MPI, and unexpected coronary event. Results: Cardiac event was observed in 56 patients; 43 PCI or CABG, and 13 unexpected events. CTA+MPI showed higher diagnostic accuracy than CTA or MPI (sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 89, 44, 28, 94%, 83, 69, 37, 91%, and 70, 81, 48, 92%, respectively). The prognosis of group1, 2, and 3 were significantly different (logrank: p&lt;0.0001) (figure). Unexpected events were also more frequent in group1 and 2 than group3 (9%vs16%vs1%, p=0.0006). Conclusion: The combination of CTA and MPI was more accurate than MPI alone for risk stratification in patients suspected CAD. Furthermore, plaque detection by CTA would be the additional valuable information to predict the cardiac event.
Phase I/II trial of twice-daily temozolomide and celecoxib for treatment of relapsed malignant glioma: Final data
Authors: S. C. Pannullo, J. Burton, J. Serventi, P. Stieg, H. Subramanian, R. Elsoueidi, I. El-Jassous, C. Balmaceda
Journal: Journal of Clinical Oncology (2006)

1519 Background: Anaplastic astrocytoma (AA) and Glioblastoma multiforme (GBM) overexpress COX-2 enzyme. COX-2 inhibitors demonstrate preclinical efficacy in glioma models and have non-overlapping toxicity with chemotherapy, prompting a phase I/II trial for patients with recurrent/progressive AA or GBM utilizing a regimen of combined temozolomide (TMZ) and celecoxib (CEL). Final survival data is presented. Methods: For phase I, TMZ was given as a fixed loading dose of 200 mg/m 2 followed by 9 doses of 90 mg/m 2 BID for 5 days. CEL was given in 5 dose levels starting at 60 mg/m 2 BID, escalating to 240 mg/m 2 BID (maximum 400 mg BID) for 10 days. Cycles were repeated every 28 days until disease progression or toxicity occurred. Results: 46 patients (28 M, 18 F) received 247 cycles of therapy. 37 patients had GBM, 9 AA. Prior treatment was radiation (N=46) and chemotherapy (N=12). No patient received prior TMZ. Median age was 54 years (range 34–74). No dose-limiting toxicity was observed. Hematologic toxicity was mild with Grade 3/4 neutropenia occurring in 3/235 cycles and Grade 3 thrombocytopenia in 3/235 and did not recur following TMZ dose reduction. Grade 1/2 constipation was common, occurring in 28% of patients. No thrombotic events occurred. Overall response rate after 6 cycles was 72%, with 1/18 (5.6%) CR, 7/18 (38.9%) PR, 5/18 (27.8%) SD, and 5/18 (27.8%) PD. Average duration of response was 6 months (range 2–15). Median survival (MS) from time of trial entry for recurrent disease was 8 months (8 months for GBM, 10 months for AA). MS from initial tumor diagnosis was 15 months (15 months GBM, 23 months AA). Conclusion: A regimen of twice-daily TMZ and CEL is safe and potentially effective for the treatment of recurrent/progressive GBM and AA. This combination warrants further study, especially in patients newly diagnosed, given the current use of TMZ in newly diagnosed GBM and the possible value of COX-2 inhibitors in the upfront setting. [Table: see text]
Abstract 16896: Kinin-Mediated Recruitment of Circulating Endothelial Supporting Cells is Impaired in Patients with CAD or Diabetes: Impact on Endothelial Healing
Authors: Nicolle Kraenkel, Kira Kuschnerus, Maja Mueller, Timo Speer, Sylvie Briand, Michael Bader, Paolo Madeddu, Francois Alhenc-Gelas, Thomas F Luescher, Ulf Landmesser
Journal: Circulation (2011)

Purpose: We have investigated the role of vascular-derived kinins for the recruitment of angiogenic monocytes and circulating angiogenic progenitor cells (CPC) to the vessel wall, and the functionality of this mechanism during coronary artery disease (CAD) and type 2 diabetes mellitus (T2D). Methods: Expression of the kinin B2 receptor (B2R) on peripheral blood mononuclear cell (PBMC) subsets of CAD patients with or without T2D, and age- matched healthy subjects (HS) was assessed by flow cytometry. Adhesion to an endothelial monolayer and subsequent healing of a scratch gap in the endothelium was studied in vitro. In vivo, recruitment of systemically injected human PBMC to injured carotid endothelium was assessed in a mouse model. B2R blockade by icatibant or B2R deficient bone marrow cells (B2R-/- BMC) were used in those analyses to verify the relevance of the B2R. Results: In HS PBMC, B2R was low expressed (&lt;1000MFI) on CD14hi inflammatory monocytes and highest in angiogenic Tie2+ or KDR+ monocytes and in KDR+ or CXCR4+ angiogenic CPCs (2517 to 7516MFI; P&lt;0.05 vs. CD14hi). Recruitment of healthy CXCR4+ CPC to the endothelium was blocked by B2R inhibition in vitro (-67% vs. vehicle, P&lt;0.05) and in vivo (-58% vs. vehicle; P&lt;0.05), while adhesion of CD14hi monocytes was unchanged, indicating a critical role of B2R for vascular homing of CPCs, but not of CD14hi monocytes. Kinin receptor expression on CXCR4+ PC was reduced in CAD patients with or without T2D (-75% vs. H; P&lt;0.05). Endothelial recruitment of CXCR4+ PC from T2D patients was markedly impaired and not regulated by the B2R. In vitro, endothelial gap closure was, partially mediated by the B2R during adhesion of healthy PBMC, which was lost in patients with T2D PBMC. Adenoviral B2R overexpression increased in vitro endothelial healing, while silencing of B2R abolished the recruitment and acceleration of gap closure by healthy CPC. In vivo endothelial healing was impaired in B2R-/- derived BMC that were transplanted in mice with endothelial injury (24.7% vs. 36.1%, P&lt;0.05). Conclusions: We newly describe that vascular kinins recruit endothelial-supportive circulating cells to the vessel wall via B2R on the circulating cell. The loss of B2R on those cells might contribute to the loss of endothelial function in T2D.