tbuckley/cabot-search huggingface dataset:
FOXO3 Variants Are Associated With Lower Fetal Hemoglobin Levels In Children With Sickle Cell Disease
Authors: Vivien A Sheehan, Jacy R Crosby, Aniko Sabo, Thad A Howard, Donna M. Muzny, Jeffrey G Reid, Banu Aygun, Eric Boerwinkle, Richard A. Gibbs, Russell E. Ware
Journal: Blood (2013)
Five-year risk for advanced colorectal neoplasia after initial colonoscopy according to the baseline risk stratification: a prospective study in 2452 asymptomatic Koreans
Authors: S. J. Chung, Y. S. Kim, S. Y. Yang, J. H. Song, D. Kim, M. J. Park, S. G. Kim, I. S. Song, J. S. Kim
Journal: Gut (2011)

Postpolypectomy surveillance guidelines for colorectal cancer introduced the concept of 'risk stratification'; however, few studies have been conducted for validation of its usefulness. The aim of this study was to assess the 5-year incidence of advanced neoplasia recurrence based on the risk stratification scheme of the guidelines and to identify its risk factors.A prospective study of surveillance colonoscopy after screening colonoscopy was carried out at the Seoul National University Hospital Healthcare System Gangnam Center. 3803 asymptomatic Koreans aged 50-69 were enrolled prospectively and 5-year cumulative adenoma rates were analysed according to three risk groups: normal (no baseline adenoma), low-risk (1-2 adenomas <10 mm) and high-risk (an advanced adenoma or ≥ 3 adenomas) groups. The RR was computed by HR using Cox proportional regression after multivariate adjustments. The primary outcome was the 5-year cumulative rate of recurrent advanced adenoma in each risk category and the secondary outcome was its predictive factors.Among 3803 subjects enrolled between 2003 and 2005, 2452 were followed-up within 5 years: 1242, 671 and 539 in the normal, low-risk and high-risk groups, respectively. Compared with the normal group, the low-risk group had a sufficiently low 5-year incidence and did not show an increased risk for subsequent advanced adenoma (2.4% vs 2.0%, HR=1.14, 95% CI 0.61 to 2.17). Conversely, a significantly higher 5-year rate (12.2%) and early recurrence (4.6, 7.4 and 9.6% at 1, 2 and 3 years) of advanced adenoma were revealed in the high-risk group. Among various patients and adenoma characteristics, only high-risk adenoma (HR=5.95, 95% CI 3.66 to 9.68) along with a number of ≥ 3 (HR=3.06, 95% CI 1.51 to 6.57) and size ≥ 10 mm (HR=3.02, 95% CI 1.80 to 5.06) were independent predictors.The surveillance interval for low-risk patients could be extended beyond 5 years. Colonoscopic surveillance should be targeted to high-risk patients, and 3-year follow-up after initial polypectomy may be appropriate.
Abstract 9422: T-Type Calcium Channel Inhibitor Attenuates Cardiac Dysfunction, Improves Cardiac Sympathovagal Imbalance and Decreases Mortality in Iron-Overloaded Mice
Authors: Sirinart Kumfu, Siriporn Chattipakorn, Suthat Fucharoen, Nipon Chattipakorn
Journal: Circulation (2011)

Excess plasma iron can lead to iron deposition in many organs including the heart. In thalassemia, excess cardiac iron deposition can cause cardiac dysfunction and depressed heart rate variability (HRV). Recently, T-type calcium channel (TTCC) has been shown as a possible gateway for iron entry in thalassemic cardiomyocytes. However, the role of TTCC in “in vivo” with iron overload has never been investigated. We tested the hypothesis that TTCC blocker can improve impaired cardiac function and attenuate the depressed HRV, leading to decreased mortality in iron-overloaded mice. Methods: C57/BL6 adult mice were fed with either normal diet (control group) or diet supplemented with dicyclopentadienyl iron (FE group) for 90 days to induce iron overload condition. Then, mice in each group were divided into subgroups being treated with L-type calcium channel (LTCC) blocker, verapamil and nifedipine; TTCC blocker, efonidipine; or iron chelator deferoxamine (DFO) for 30 days. Pressure-volume (P-V) conductance catheter system was used for cardiac function assessment. HRV was determined at baseline and at the end of treatment in all mice. Results: Iron-overloaded mice demonstrated impaired cardiac function as shown by decreased stroke volume (SV), cardiac output (CO), ejection fraction (EF), impaired HRV as indicated by increased LF/HF ratio, with high mortality rate (Figure). Efonidipine effectively improved cardiac function impairment, whereas LTCC blockers and DFO did not. Efonidipine and DFO also significantly improved HRV parameter, whereas LTCC blockers could improve it at a lower extent. Both efonidipine and DFO markedly decreased mortality, while LTCC blocker did not, in these mice with iron overload. Conclusion: Impaired cardiac function and depressed HRV caused by iron overload were improved by efonidipine, but not by verapamil and nifedipine, suggesting that TTCC but not LTCC, plays an important role for iron uptake in the heart of iron-overloaded mice.
Abstract 1630: LAR Modulates Insulin-like Growth Factor-1-induced Endothelial Cell Signals for Growth, Migration and Tube Formation
Authors: Juxiang Li, Xilin Niu, Marschall S Runge, Nageswara R Madamanchi
Journal: Circulation (2006)

Insulin-like growth factor-1 (IGF-1) induces endothelial cell migration and promotes angiogenesis. We showed previously that leukocyte antigen-related (LAR) protein tyrosine phosphatase is a negati...
The emerging translational oncology toolkit
Authors: Stephen Friend
Journal: Clinical Cancer Research (2008)

FO01-02   Until we have better awareness of which compounds will down-modulate which modules in which patients, our probability of success will continue to be low. Until we have intermediate markers capable of driving clinical decisions in less than one to two months, the expenses associated with clinical trials will stay too high. And, finally, if we were to be able to enroll all patients being treated into trials where their samples were collected and interrogated, we could begin to do efficient, robust combination trials that will be needed to advance new therapies in a more appropriate time frame. We will discuss our efforts to move in this direction.
Abstract 19155: Cardiac Stem Cell Activation and Ensuing Myogenesis and Angiogenesis Contribute to Cardiac Adaptation following Intensity-Controlled Exercise Training
Authors: Cheryl D Waring, Angela Papalambrou, Lisa Sharp, Andrew J Smith, Saranya Purushothaman, Carla Vicinanza, David Goldspink, Daniele Torella, Bernardo Nadal-Ginard, Georgina M Ellison
Journal: Circulation (2010)

The role of cardiac stem/progenitor cells (CSCs) in the cardiac adaptation to exercise stress is undefined. We evaluated whether treadmill exercise training at different intensities can stimulate c-kit positive (c-kitpos) CSCs and their differentiation into new myocytes and microvasculature in the adult rat myocardium. To this aim, 33 male Wistar rats (∼220g) were exercised at either a low (LI; 55–60% VO2 max) or high (HI; 85–90% VO2 max) intensity for 30 min/day, 4 days/wk for up to 4 wks on motorized treadmills. Eighteen untrained rats acted as age-matched sedentary controls (CTRL). To track myocardial cell proliferation, BrdU was administered (i.p.) twice daily. Immunohistochemical and confocal microscopy analysis of the left ventricle (LV) showed an increase (P<0.05) in average myocyte diameter in exercised animals compared to CTRL. In addition to larger (hypertrophied) myocytes, smaller BrdU (3.4±0.2% LI, 7.4±0.3% HI) and Ki67 (0.8±0.1% LI, 1.0±0.1% HI) positive myocytes were observed in the LV of ex...
Abstract 21342: Angiotensin II Blockade and Beta-Blockade Combination Therapy Slows Down the Aortic Root Dilatation in Patients with Marfan Syndrome
Authors: Hsin-Hui Chiu, Mei-Hwan Wu, Jou-Kou Wang, Chun-Wei Lu, Ming-Tai Lin, Shuenn-Nan Chiu, Chun-An Chen
Journal: Circulation (2010)

Introduction: Beta-blockade, the standard treatment for Marfan syndrome (MFS), had limited effects in aortic root growth. Losartan, an angiotensin II blockade (ARB), had potential efficacy to prevent aortic root dilatation in an animal model of MFS. Hypotheses. Combination therapy with ARB and beta-blockade has synergic effects on attenuation of aortic root dilation in patients with MFS. Methods: A randomized, open-label, active control trial was conducted in National Taiwan University Hospital. From May 2007 to Jan 2010, twenty-eight patients (M/F: 12/16, 16.5 ± 6.6 years) diagnosed as MFS with recognized aortic root dilation (Z score >2.0) and under beta-blockade were enrolled and randomized into two groups. One group continued previous beta-blocker therapy. The other group received a combination therapy with beta-blocker and ARB. The study medication, Losartan, was prescribed with a starting dose and then titrated to an optimal dose in one to two weeks according to the resting heart rate and blood pres...
Public interest in child health not matched by government resources
Authors: Steven Welch
Journal: BMJ (1999)

The high priority given to child health issues by the general public has not been mirrored by the allocation of government resources, Dr James Appleyard, chairman of the British Medical Association's working party on child health, told a conference in London last week.

Child health had not featured as a specific target in either the last government's Health of the Nation white paper or the current government's Our Healthier Nation, said Dr Appleyard, …
Impact of Chronic Graft-Versus-Host disease (GVHD) After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) As Treatment for Acute Myeloid Leukemia (AML): A Survey From the Acute Leukemia Working Party of the EBMT
Authors: Frederic Baron, Myriam Labopin, Dietger Niederwieser, noel-Jean Milpied, Jan J Cornelissen, Claes Malm, Lars Vindelov, Didier Blaise, Jeroen JWM Janssen, Eefke J Petersen, Gerard Socie, Vanderson Rocha, Arnon Nagler, Mohamad Mohty
Journal: Blood (2011)
Allocating prescribing budgets
Authors: C A Ryle
Journal: BMJ (2000)

Editor—Rice et al present what they describe as a “needs based” formula for allocating prescribing budgets.1 This seems an improvement on the ASTRO-PU (age, sex, and temporary resident originated prescribing unit), which it replaces, but in view of its crucial impact on the resources available to general practitioners and their patients its limitations should be stated more clearly.

Despite its title, the formula does not assess need directly but relies on data from the national census to generate proxy measures. The association between these measures and prescribing costs “explains” observed variation in these costs only in the narrow statistical sense of the word. Bains and Parry,2 and Majeed3 point out further important limitations.

These criticisms are of more than academic importance. The formula is “needs based” only in a vague and general sense, but despite its manifold weaknesses there is a danger that NHS organisations will use it as if it were an adequate basis for budget setting and monitoring prescribing performance. The patients whose access to treatment will be thus determined and rationed will not be proxies.

Primary care groups have the difficult task of salvaging something from this minefield. If we wish to explain variations in prescribing in the full sense of the word and if we are serious about the pursuit of equity and quality, we have a great deal of work to do. Several actions spring to mind.

Firstly, computerisation gives us the means to collect detailed morbidity data at practice level. This will allow us to test the formula for allocating prescribing budgets against real measures of need and, if necessary, make allowances in practice based budgets.

Secondly, by combining prescribing and morbidity data, and auditing standards of care, we can ensure that measures of quality are built into our incentive schemes. We will also gain considerably in our understanding of the many causes of variations in prescribing costs.

Thirdly, we might consider foregoing the right to keep savings from our practice prescribing budgets. In a cash starved NHS, large handouts for cheap prescribing should be seen as the occasion for red faces rather an opportunity for red carpets.
Carcinogenesis in the Adrenal<xref ref-type="fn" rid="fn1">1</xref><xref ref-type="fn" rid="fn2">2</xref>
Authors: G W WOOLLEY
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Carcinogenesis in the Adrenal Get access George W. Woolley George W. Woolley Chief, Professor of Biology Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 717–723, https://doi.org/10.1093/jnci/15.3.717 Published: 01 December 1954
Abstract 1770: Left Ventricular Filling Curve Variables are Superior to Resting Lung to Heart Ratios in Predicting Left Ventricular End-diastolic Pressure in Patients with Preserved Systolic Function Undergoing Gated Myocardial Perfusion Imaging
Authors: Dineshkumar Patel, Vincent J Robinson, Roque B Arteaga, John W Thornton, Laura K Norman, Jimel Carpenter, Mahendra K Mandawat
Journal: Circulation (2007)

Introduction: There is a 4–5 fold increase in morbidity and mortality when diastolic dysfunction is present in patients with coronary artery disease (CAD). Thallium-201 lung/heart ratio (TLHR) at stress has been proven to capture this increased risk. Most laboratories however use technetium-99m agents for stress myocardial perfusion imaging (MPI) which prevents access to stress TLHR. Method: This is a retrospective study of 52 consecutive patients (age 58±11 years, 73% had CAD) who underwent MPI and cardiac catheterization within 15 days, without interval change in medication or intervention. All patients had ejection fraction ≥45% and normal sinus rhythm. Left ventricular end-diastolic pressure (LVEDP) at cardiac catheterization was recorded. From MPI, peak filling rate (PFR), time to peak filling rate (TPFR), filling rate during first 1/3 of diastole (1/3FR) were obtained using 4D-MSPECT (University of Michigan) and rest TLHR was calculated manually. Results: PFR, TPFR and 1/3FR correlated significantly with LVEDP (r= −0.53, 0.45, −0.45 and p =0.00005, 0.0008, 0.0009 respectively). Rest TLHR did not correlate with PFR, TPFR and 1/3FR (r=0.11, 0.06, 0.09 and p =0.47, 0.68, 0.55 respectively) or with LVEDP (r=0.10, p =0.49). These variables had excellent negative predictive value (NPV) of ≥90% but modest positive predictive value (PPV) of ≥54%. Since PFR did not correlate with 1/3FR (r=0.18, p =0.19), we combined these 2 variables. This combination had a NPV of 84% and improved PPV to 86% and specificity to 94%. Conclusions: Our study validates diastolic filling variables from 4D-MSPECT showing excellent correlation with LVEDP at cardiac catheterization ( p ≤0.0009). PFR, TPFR and 1/3FR are superior to rest TLHR and they have excellent sensitivity (≥82%) and specificity (≥63%) for detecting LVEDP ≥18mmHg. Hence, a valid methodology of combining the risk of perfusion defects with diastolic impairment can be achieved by adding PFR, TPFR and 1/3FR to MPI results. Receiver Operated Characteristic Curve Analysis
Abstract 9048: Once-Daily Esomeprazole 20mg Prevents Recurrence of Peptic Ulcer in East Asian Low-Dose Aspirin Users at Gastrointestinal Risk: the LAVENDER Study
Authors: Shinya Goto, Yasushi Okada, Myung-Gyu Choi, Jaw-Town Lin, Yoshikazu Kinoshita, Hiroto Miwa, Chern-En Chiang, Kentaro Sugano
Journal: Circulation (2012)

Objectives: Gastroprotective therapy is recommended for cardiovascular (CV) patients (pts) taking low-dose aspirin (LDA) and at increased gastrointestinal risk, eg history of peptic ulcer. This study assessed the potential effects of esomeprazole (ESO) in prevention of recurrent peptic (gastric and/or duodenal) ulcer in East Asian pts taking LDA for CV protection. Methods: Pts aged &gt;=20y with history of endoscopically confirmed peptic ulcer and taking LDA (81-324mg/d) for CV protection were enrolled ( NCT01069939 ). Pts with serious heart failure/unstable hypertension/history of acute coronary syndromes were excluded. Eligible pts were randomized to ESO 20mg/d or placebo (PBO) for a maximum of 72 wks. All pts received concomitant mucosal protection (gefarnate 100mg/d). Primary end point was time to ulcer recurrence, analyzed by the Kaplan-Meier method. Findings are presented up to wk 60, as per a planned event-driven analysis. Results: A total of 427 pts (mean age 67y; 79% men) comprised the full analysis set (ESO, n=213; PBO, n=214). There was a statistically significant difference in the time to ulcer recurrence between ESO and PBO (hazard ratio, 0.14; 96.65% CI: 0.04-0.42; p&lt;.001). Estimated ulcer-free rate up to wk 60 was 96.0% and 75.8%, respectively. Sub-analysis showed superior ulcer-free rates for ESO vs PBO regardless of LDA dose (81mg, 100mg, and &gt;100mg) and reason for LDA treatment (primary vs secondary prevention). Treatment with ESO was well tolerated. The rate of serious cardiac-related adverse events with ESO was similar to PBO (1.4% and 1.9% of pts, respectively). No deaths were reported. Conclusions: Daily ESO 20mg is efficacious and well tolerated for reducing the recurrence of peptic ulcer in East Asian pts who have a history of ulcers and are taking LDA for cardioprotection. Supported by AstraZeneca K.K., Osaka, Japan. Medical writing support from in Science Communications was funded by AstraZeneca.
Graft TCR-Alpha/Beta Depletion and Peri-Transplant Use Of Eculizumab In Matched Unrelated Donor Transplantation For Severe Aplastic Anemia-Paroxysmal Nocturnal Hemoglobinuria: Report Of Two Cases
Authors: Michael Maschan, Larisa Shelikhova, Elena Kurnikova, Elena Boyakova, Alexey Levadnyy, Yakov Muzalevskii, Vlasta Bobrynina, Varvara Kalinina, Irina Kalinina, Dina Baidildina, Dmitriy Balashov, Galina Novichkova, Alexey Maschan
Journal: Blood (2013)
FDG PET/CT Imaging of an Isolated Recurrence in the Eyelid of a Patient With Follicular Lymphoma
Authors: Ozgul Ekmekcioglu, Betul Vatankulu, Resit Akyel, Mustafa Ozbayrak, Kerim Sonmezoglu
Journal: Clinical Nuclear Medicine (2015)

An 80-year-old woman had a history of follicular lymphoma diagnosed by biopsy of the inguinal lymph node 4 years prior. After systemic chemotherapy, she achieved complete remission. She presented with painless swelling on the left side of the eyelid. She also had suspicious lymph node enlargement in the cervical and axillary regions. FDG PET/CT showed an isolated FDG-avid lesion on the eyelid that was confirmed by biopsy to be compatible with lymphoma recurrence.
BLAST: A Confirmatory, Single-Arm, Phase 2 Study of Blinatumomab, a Bispecific T-Cell Engager (BiTE®) Antibody Construct, in Patients with Minimal Residual Disease B-Precursor Acute Lymphoblastic Leukemia (ALL)
Authors: Nicola Goekbuget, Hervé Dombret, Massimiliano Bonifacio, Albrecht Reichle, Carlos Graux, Violaine Havelange, Eike C. Buss, Christoph Faul, Monika Bruggemann, Arnold Ganser, Julia Stieglmaier, Hendrik Wessels, Vincent Haddad, Gerhard Zugmaier, Dirk Nagorsen, Ralf C. Bargou
Journal: Blood (2014)
HSV thymidine kinase gene transduction enhances tumor growth rate, neovascularization and cyclooxygenase-2 expression in murine colon cancer xenografts.
Authors: Alexander Konson, Abraham Danon, Gilad Rimon, Riad Agbaria
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3424 

Transduction of tumor cells with Herpes Simplex virus type I thymidine kinase (HSV-tk) gene and subsequent treatment with the prodrug ganciclovir (GCV) is the most common system studied for “suicide” gene therapy of cancer. However, the HSV-tk/GCV strategy has several limitations that, to some extent, plague all the cancer gene therapy strategies. Limitations include low transduction efficiency, vector cytotoxicity, high immunogenicity of transduced cells and resistance or loss of GCV sensitivity. In the present report we show that HSV-tk gene transduction significantly augments tumor growth rate (1.63±0.15 fold increase in mean tumor volume) and neovascularization (1.83±0.32 increase in mean intratumor microvessel density) in xenografts of murine colon cancer cells. Transduction of tumor cells with control vector carrying the neomycin resistance gene alone did not increase tumor growth rate but even decreased it, indicating that the observed phenomenon is related to the presence of the HSV-tk sequence insert in the retroviral vector used for HSV-tk gene delivery. Additionally, we demonstrate herein that HSV-tk gene transduction significantly enhances cyclooxygenase-2 (COX-2) expression and leads to 2.5±0.17 fold increase in prostaglandin E2 release in tumors ex vivo. Tumor growth rate of HSV-tk transduced murine colon cancer xenografts was significantly inhibited by treatment with the selective COX-2 inhibitor nimesulide. This observation may suggest a causal relationship between COX-2 overexpression and the enhanced growth rate of tumors expressing HSV-tk gene. It is further shown that the enhanced tumor growth rate observed in HSV-tk transduced murine colon cancer xenografts persists upon the development of GCV resistance, characterized by decreased susceptibility of resistant cells to the antiproliferative effect of GCV. Thus, one may expect the prognosis of HSV-tk transduced tumors to seriously deteriorate when they become resistant to GCV since tumor growth rate is enhanced, without a benefit of a prodrug to accomplish the suicide mission of this treatment. Taken together, these results may provide an insight to further understanding of the direct effect of HSV-tk gene transduction on tumor cell biology as well as to potential harmful effects of “suicide” gene therapy using retroviral vectors.
Mathematical approach for understanding deagglomeration behaviour of drug powder in formulations with coarse carrier
Authors: Irene Parisini, James L. Collett, Darragh Murnane
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Deagglomeration of cohesive particles in combination with coarse carrier is a key requirement for inhaled formulations. The aim of the project was to propose a mathematical approach to understand aerosolization behaviour of micronized particles alone and in formulation with carriers. Salbutamol sulphate and salmeterol xinafoate were blended separately with fine lactose (ratio 1:4) and fine and coarse lactose (1:4:63.5). Laser diffraction was employed to characterize the powder median particle size. The deagglomeration of micronized materials followed an asymptotic monoexponential relationship. When the coarse lactose was added, the relationship fitted a bi-exponential equation showing an easily and a poorly dispersed fraction. Using model hydrophobic and hydrophilic APIs, this study has demonstrated the utility of an analytical approach that can parameterize deagglomeration behaviour of carrier-free and carrier-based inhalation formulations. The analytical approach provides the ability to systematically study the effect of material, formulation and processing factors on deagglomeration behaviour.