tbuckley/cabot-search huggingface dataset:
Abstract #LB-226: IL-18 gene polymorphisms and colorectal cancer risk among atomic bomb survivors
Authors: Tomonori Hayashi, Yukari Morishita, Hiroko Nagamura, Mayumi Maki, Yoichiro Kusunoki, Kengo Yoshida, Kei Nakachi
Journal: Cancer Research (2009)

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

Atomic bomb (A-bomb) radiation exposure has resulted in long-term health effects in survivors, increasing risk of such inflammation-related diseases as cancer with increase of radiation dose. We have thus far elucidated that A-bomb radiation diminished immune function and accelerated inflammatory status, thereby reporting on possible involvement of such accelerated inflammation in the onset of cancer/non- cancer diseases observed among A-bomb survivors. In this study, we investigated possible involvement of cytokine gene polymorphisms in the development of radiation-related colorectal cancer, using a case-control study design in an A-bomb survivor cohort. We determined genotypes of an inflammatory cytokine gene, IL-18, in 210 colorectal cancer cases (70 proximal colon cancer cases, 88 distal colon cancer cases, 45 rectal cancer cases, and seven cases of cancer in unknown or boundary segments) developing in 1982 or later, and 843 controls from the Adult Health Study cohort of the Radiation Effects Research Foundation. We identified a haplotype block containing two htSNPs (main haplotype alleles: IL18-AT, IL18-CG) in the IL-18 promoter region, and evaluated risk for colorectal cancer by site (i.e., colon and rectum) and by IL-18 haplotype, in a case-control study. A multiple regression analysis showed: 1) that radiation-associated risk increase was significant for colon cancer (OR=1.33/Gy, 95%CI: 1.10-1.60) but not for rectal cancer; and 2) that individuals with IL18-CG allele homozygotes, compared to those with the IL18-AT allele, showed significantly higher risk for colon cancer (OR=1.71, 95%CI: 1.13-2.59) but not for rectal cancer. When the subjects were divided into three subgroups relative to radiation dose for estimation of odds ratio by IL-18 haplotype, significant increase in colon cancer risk (OR=3.58, 95%CI: 1.81-7.10) was observed for those with IL18-CG allele homozygotes in the highest dose group (>0.7 Gy). These results suggest that colon cancer risk for A-bomb survivors might depend on both IL-18 haplotype and radiation dose. A further investigation into colon cancer and radiation exposure will be required in terms of subsites or/and MSI (CIN) status.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-226.
Physical activity and survival after breast cancer diagnosis
Authors: Michelle D. Holmes, Wendy Y. Chen, Diane Feskanich, Candyce H. Kroenke, Graham A. Colditz
Journal: Cancer Research (2004)

0.80 (95% confidence interval [CI], 0.60-1.06) for 3 to 8.9 MET-hours per week; 0.50 (95% CI, 0.31-0.82) for 9 to 14.9 MET-hours per week; 0.56 (95% CI, 0.38-0.84) for 15 to 23.9 MET-hours per week; and 0.60 (95% CI, 0.40-0.89) for 24 or more METhours per week (P for trend = .004). Three MET-hours is equivalent to walking at average pace of 2 to 2.9 mph for 1 hour. The benefit of physical activity was particularly apparent among women with hormone-responsive tumors. The RR of breast cancer death for women with hormone-responsive tumors who engaged in 9 or more METhours per week of activity compared with women with hormone-responsive tumors who engaged in less than 9 MET-hours per week was 0.50 (95% CI, 0.34-0.74). Compared with women who engaged in less than 3 MET-hours per week of activity, the absolute unadjusted mortality risk reduction was 6% at 10 years for women who engaged in 9 or more MET-hours per week.
Abstract 17081: Risk Factors for Developing Takotsubo Cardiomyopathy
Authors: Abhishek Deshmukh, Gagan Kumar, George Dibu, Sameer Raina, Freij Gobal, Chiranjit Rihal, Jawahar L Mehta
Journal: Circulation (2011)

Background: Takotsubo cardiomyopathy (TTC) has emerged as a new clinical entity which has not been fully understood. Numerous case reports exist regarding association of TTC with high adrenergic state conditions like Pheochromocytoma. Our aim was to explore the association of common medical conditions with TTC. Methods: This was a cross sectional study using the National Inpatient Sample (NIS) 2007 database.TTC or Broken heart syndrome or Reversible left ventricular dysfunction following sudden emotional stress or Stress induced cardiomyopathy or Transient left ventricular apical ballooning syndrome was defined as patients discharged with any ICD code of 429.83 ( http://www.cdc.gov/nchs/data/icd9/agendasept05.pdf ). The common medical conditions were identified by appropriate ICD 9 codes Results: We indentified total 6229 discharges with any discharge diagnosis of TTC. The likelihood of common medical conditions with TTC is shown in Table 1. Conclusions: This is the first study to explore the association of common medical conditions associated with TTC on a nationwide basis. We conclude that the patient with hyperlipidemia, smoking, pulmonary hypertension, sub arachnoid hemorrhage, migraine, hyperthyroidism, collagen vascular diseases, anxiety state, and stress have higher odds of developing TTC. Further research needs to be done for better understanding the causes and pathophysiology of TTC which in turn will help risk stratification and define optimal therapy.
Abstract A102: Combination treatment with hypoxia-activated prodrug TH-302 and radiation reduce pancreatic tumor initiating cells and tumor growth in patient-derived xenografts
Authors: Ines Lohse, Joanna Rasowski, Pinjian Cao, Melania Pintilie, Trevor Do, Emin Ibrahimov, Ming-Sound Tsao, Richard P. Hill, David W. Hedley
Journal: Cancer Research (2015)

Abstract Rationale: Using orthotopically-grown primary pancreatic cancer xenografts we recently identified an association between hypoxia and spontaneous metastasis formation, and we hypothesized that metastatic potential is conferred by the presence of tumor-initiating cells (TIC). We therefore investigated the relationship between hypoxia, tumor growth and TIC, and examined the effect of the hypoxia-activated prodrug TH-302 and ionizing radiation (IR) on pancreatic TIC and tumor growth. Methods: Eleven patient-derived pancreatic cancer xenograft models were used to examine tumor-initiation potential in relation to the tumor phenotype. To examine the effect of TH-302 and IR on TIC, tumor-bearing mice were treated with 50 mg/kg or 150 mg/kg TH-302, 10Gy of IR, or with the combination of TH-302 and IR. To examine the effect of TH-302 and IR on tumor growth, mice were treated with either TH-302 or IR alone, or with the combination treatment according to a clinically relevant schedule. Animals were treated with 50mg/kg TH-302 injected ip on days 1, 5 and 9 and/or 2Gy irradiation per day on days 2, 3 and 4. Tumor hypoxia was measured by EF5 administration and immunostaining. Results: TIC frequency varied across the patient-derived xenograft models and rapid tumor growth was strongly correlated with high TIC frequency but not hypoxia. Treatment with TH-302 in combination with IR led to a significant reduction in TIC frequency compared with either treatment alone in all models tested. Treatment-induced reduction in TIC frequency was independent of the magnitude of tumor hypoxia. Treatment-induced reduction of tumor growth was only observed in fast-growing hypoxic models. Additionally, TH-302 treatment also induced DNA damage in tumor tissue adjacent to the hypoxic zone which is consistent with the previously demonstrated bystander effect of TH-302. Conclusions: These results suggest that TIC can reside in both the oxic and the hypoxic microenvironment and that the combination of TH-302 and IR may present a novel therapeutic strategy to reduce the frequency of TIC and tumor growth rate of pancreatic tumors. Citation Format: Ines Lohse, Joanna Rasowski, Pinjian Cao, Melania Pintilie, Trevor Do, Emin Ibrahimov, Ming-Sound Tsao, Richard P. Hill, David W. Hedley. Combination treatment with hypoxia-activated prodrug TH-302 and radiation reduce pancreatic tumor initiating cells and tumor growth in patient-derived xenografts. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A102.
Abstract 1667: Early Childhood Mental Development After Transfusion-free Cardiac Surgery On Cardiopulmonary Bypass: A Multi-institutional Study
Authors: Tomohiko Ukai, Takenori Adachi, Atsusi Numaguchi, Daichi Fukumi, Toshiaki Yasuda, Hiroki Hasegawa, Jyun Yokote, Miwako Kado, Masami Nagashima, Masanobu Maeda
Journal: Circulation (2007)

Background: The use of blood products is often necessary to prime the extracorporeal circuits for pediatric cardiac surgical patients. The use of blood products carries serious risks both in the acute and long-term aspects of patient care. However, excessive hemodilution during cardiopulmonary bypass (CPB) is associated with decreased oxygen carrying capacity, edema, and organ dysfunction. Especially, whether brain dysfunction after transfusion-free cardiac surgery on CPB occurred is unknown. Objective: This study aims to investigate whether excessive hemodilution affects child’s mental development. Methods: We studied 143 infants (24.2 +/− 15.8 months, 5 months ~ 3 years of age) had performed surgical closure of ventricular septal defect (VSD) in less than 12 months (4.8 +/− 2.6 months) of age in 7 children’s hospitals. Questionnaires mailed to the parents included the Tsumori-Inage Infant Developmental Scale estimating subjects’ behavioral developmental level as Developmental Quotients (DQ). The infants were divided into 3 groups; transfusion-free (Group A, n=52), transfusion during CPB (Group B, n=24) and transfusion after CPB (Group C, n=66). Results: Lower DQ was found for Group A (94.7 +/− 11.6) than Group B (103.5 +/− 16.0, p=0.008) and Group C (101.7 +/− 17.9, p=0.016). No correlation was found between DQ and minimum hemoglobin level during CPB (min-Hb) in Group A. The DQ was likely to be lower in the infants with below 6 g/dl (93.0 +/− 13.0) than with over 6 g/dl (98.7 +/− 8.3. p=0.10) of min-Hb. Conclusions: The results suggest that the infants after transfusion-free surgery of VSD on CPB delay in the mental development in their early childhood. Maintaining minimum hemoglobin level over 6 g/dl during CPB seems to prevent the mental development from delay.
Records prematurely destroyed
Authors: M M Hawkins, A W Craft
Journal: BMJ (1995)

health care and its evaluation have led to the expectation that studies of use of health services will become prominent.It would be deplorable if unreasonable procedures regarding access to data were to hinder practical applications of health record linkage.Some people will undoubtedly argue that the consent of each subject should be obtained for any procedure that links records.We believe that governments, as custodians of health care data- bases, have a duty to allow scientific investigators access to them in view of the benefits that have resulted from previous studies based on these databases.A requirement for individual consent would lead to the extinction of useful research using health care databases.
Global health agencies' response to malaria
Authors: A. Attaran
Journal: BMJ (2001)

# Panel should be set up to review malaria control proposals from endemic countries {#article-title-2} EDITOR—A news item about the Oxford 2000 conference on tropical medicine reports my address at the meeting.1 Readers may have been left with a negative impression of Roll Back Malaria from Yamey's précis of my remarks. I therefore wish to underscore my view that this is an extremely important and impressive global project, which has the promise to reinvigorate the global effort to control the disease. My colleagues and I at the Center for International Development at Harvard greatly applaud the effort; indeed we have worked closely with Roll Back Malaria in preparing some of the background analysis of the heavy economic burden of malaria in Africa. The purpose of my remarks was to emphasise the need for Roll Back Malaria and the donor agencies that are partners within it to implement an independent, scientifically driven review panel under the auspices of the World Health Organization. Such a panel would screen malaria control proposals from endemic countries and would urge ample and immediate funding for those thought likely to achieve success. Such an arrangement would serve as a quality check that malaria control projects are scientifically sound. The fact that the projects have passed scrutiny would help give donors confidence that they can commit the much larger funds needed for malaria control without them being wasted. 1. 1.↵1. Yamey G .Global health agencies are accused of incompetence.BMJ2000; 321:787. (30 September.) [OpenUrl][1][FREE Full Text][2] # Agencies dispute Attaran's view of Roll Back Malaria initiative {#article-title-4} EDITOR—The Roll Back Malaria initiative strives … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DYamey%26rft.auinit1%253DG.%26rft.volume%253D321%26rft.issue%253D7264%26rft.spage%253D787%26rft.epage%253D787%26rft.atitle%253DGlobal%2Bhealth%2Bagencies%2Bare%2Baccused%2Bof%2Bincompetence%26rft_id%253Dinfo%253Apmid%252F11009511%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=321/7264/787&atom=%2Fbmj%2F322%2F7279%2F174.atom
Abstract 2450: Long-term Clinical Follow-up After Rotational Atherectomy to Coronary Arterial Stenosis in Kawasaki Disease
Authors: Hiroyoshi Yokoi, Masashi Iwabuchi, Hitoshi Yasumoto, Hideyuki Nosaka, Masakiyo Nobuyoshi
Journal: Circulation (2006)

Background: Although rotational atherectomy (RA) have been proven to be effective in calcified and non-dilatable lesions in Kawasaki disease, long-term efficacy and safety have not been established...
CF102 an A3 adenosine receptor agonist induces in vivo apoptosis of Hepatocellular carcinoma
Authors: Sara Bar Yehuda, Salomon Stemmer, Lea Madi, David Castel, Avivit Ochaion, Shira Cohen, Faina Barer, Alexander Zabutti, Georginia Perez-Liz, Luis Del Valle, Pnina Fishman
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5712 

The A3 adenosine receptor (A3AR) is highly expressed in solid tumors and has been suggested as a potent target for cancer treatment. In this study we first show that both human and rat Hepatocellular Carcinoma (HCC) cells highly express the A3AR and that CF102, a highly selective agonist to the receptor induces apoptosis of HCC in vivo .    Increased A3AR expression levels were detected in tumor tissues and in peripheral blood mononuclear cells (PBMCs) derived from patients with HCC. Similar data was observed in N1S1 HCC tumor bearing rats, demonstrating that A3AR expression levels in the PBMCs reflect receptor status in the remote tumor. The high expression level of the receptor was directly correlated to over expression of NF-κB, known to act as a transcription factor of A3AR.    To explore whether A3AR may be utilized as a specific target to combat HCC, CF102 was administered orally thrice daily to N1S1 tumor bearing rats. CF102 induced marked dose response inhibition of tumor growth via de-regulation of the NF-κB and the Wnt signal transduction pathways, resulting in apoptosis of tumor cells.Taken together, A3AR is highly expressed in tumors and PBMCs of HCC patients and tumor bearing rats. CF102 targets the A3AR, to induce apoptosis and tumor growth inhibition.    The NF-κB signal transduction pathway is involved in receptor expression and functionality. These data suggest A3AR as a novel biomarker target therapy to be developed for the treatment of HCC.
Abstract 2256: Myocardial Blood Flow and Viability in Children With Transpositon of the Great Arteries After Arterial Switch Operation Assessed With Magnetic Resonance Imaging
Authors: Carsten Rickers, Michael Jerosch-Herold, Janina Marienfeld, Inga Voges, Chris Hart, Michael Helle, Hans Heiner Kramer
Journal: Circulation (2009)

Introduction:  Coronary complications represent an important risk factor for sudden cardiac death and infarction late after arterial switch operation (ASO) in children with transposition of the great arteries (TGA). Therefore, we sought to investigate regional myocardial blood flow distribution and viability in TGA pts using cardiac magnetic resonance (CMR).   Methods:  In 32 TGA patients post ASO (age: 12,4 ±5,3 yrs) CMR first-pass perfusion imaging (0.03 mmol/kg Gd-DTPA; TR/TE/ α =2.6/1.1/20°) and late gadolinium enhancement (LDE) imaging for viability assessment using an ECG triggered 3D inversion recovery sequence (TR/TE/ α = 3.7/1.8/15°) was applied using a 3 Tesla MR-scanner (Philips, Achieva). These findings were compared to regional wall motion measurements from short axis cine imaging. Seventeen age and gender- matched heart healthy children who underwent MRI for neurological indications served as controls. Seven TGA pts were suspicious of or known to have coronary artery stenosis or occlusion. Quantitative myocardial blood flow at rest and stress (Adenosin 140 mcg/kg/min) was calculated in 6 LV segments per slice (2–3 slices/pt) using a model independent deconvolution. CMR results were compared to conventional x-ray guided coronary angiography in all pts.   Results:  In 6 patients myocardial stress blood flow was significantly reduced at stress due to an occlusion of the left coronary artery (LCA) in 4, and a hypoplastic left anterior descending artery in 2. Scar tissue (i.e. LGE) was detected in the antero-septal region of 2 pts with an occluded LCA. One of those patients (14 yr female) received minimal invasive coronary artery bypass surgery and one pt (22 yr male) a conventional mammary artery bypass. Myocardial perfusion reserve (MPR=hyperemic: resting flow) in pts with morphological normal coronary arteries (n=25) was significantly reduced as compared to heart healthy children (2,6 ±0,7 vs 3,4 ±0,9; p   Conclusions:  In children post arterial switch operation myocardial ischemia and scar tissue can be detected with CMR to guide further therapy. The global impairment of coronary flow reserve in these pts, compared to healthy hearts may indicate altered vasoreactivity due to coronary reimplantation.
Informed consent
Authors: N. Pfeffer, P. Alderson, H. Campbell, K. M Boyd, S. A M Surry, T. Cullinan, S B Squire, R Hawley, S Macfarlane, S Agbaje, N J Beeching, G B Wyatt, K D. Koning, N Gray, C Hayward, A Ali, A E Bianco, M Taylor, B Brabin, J B S Coulter, M d. B. Daly, D. Elbourne, C. Snowdon, J. Garcia, K. Epstein, B. Sloat, K. Mohanna, T. Woodcock, J. Norman, J. Sikorski, R. Watson, P. Wilson, A. House, P. Knapp, C. Williamson, G. C Sutton, L. Garvican, R. Wilson, A. Malin, D. Lockwood, S W P Mhlongo, G V Mdingi, R. Ashcroft, B. Toth, J. Mant, S. Winner, J. Carter, D. T Wade, D J Stott, P Langhorne, H Rodgers, D. Rutter, T. Brewin, D. Barer
Journal: BMJ (1997)

The central problem is often poor design and conduct of trialsEditor-We are concerned about some aspects of the recent articles on consent. 1 2 Len Doyal claims that informed consent may not be necessary for three most vulnerable groups: young children, patients with learning difficulties, and unconscious or semiconscious patients.Yet young children (unlike all adult groups) have the protection of their parents' consent, and this should always be respected. 3 The other two groups show the limitations of applying Kantian respect for autonomy, designed for property owning 18th century gentlemen, to vulnerable dependent patients.There is an urgent need to agree new ways of making research decisions with and for these minority groups.As is usual in arguments against seeking informed consent, there is a tendency to concentrate on dramatic extremes: patients with severe mental impairment and patients receiving heroic cancer treatment.The development of principles from extremes is dangerous and should be discouraged.Difficulties with relatively small groups should not be used to excuse researchers from requesting the consent of the vast majority of the millions of people every year who help with research into mundane pharmaceutical trials of treatments of arthritis or everyday misery.A deeper problem with the articles is the assumption that consent is the central problem in research.We suggest that, more often, the central problem is the poor design and conduct of trials which alienate or distress people on whose practical support researchers depend.The solution here is not to tinker with consent but to clean up research.Health service users could help at every stage of clinical research: the selection of questions worth investigating; the design and conduct of trials, including the information materials; the interpretation and reporting of the evidence; dissemination; and working with practitioners to put findings into practice.Consumers for Ethics in Research has been working with health service users, researchers, and practitioners on these issues for the past eight years, partly through regular open meetings, during which many practical ideas have been advanced.
Abstract 9390: Rapid Effects of Personal-Level Ambient Fine Particulate Matter Exposure on Arterial Hemodynamics and Vascular Function during the Same Day
Authors: Robert D Brook, Hwashin H Shin, Robert L Bard, Richard T Burnett, Alan Vette, Carry Croghan, Jonathan Thornburg, Charles Rodes, Ron Williams
Journal: Circulation (2010)

Background: Ambient fine particulate matter < 2.5 μm (PM2.5) levels are associated with alterations in arterial hemodynamics and vascular function one or more days later. However, the characteristics of the same-day rapid exposure-response relationships within hours of exposures remain unclear. Objectives and Methods: We aimed to explore the effects of personal PM2.5 exposures within the preceding 24 hours on blood pressure (BP), heart rate (HR), brachial artery diameter (BAD), endothelial function (flow-mediated dilatation (FMD)) and nitroglycerin-mediated dilatation (NMD). Fifty-one non-smoking general population subjects living in Wayne County Michigan, who were participating in the Detroit Exposure and Aerosol Research Study conducted by the Environmental Protection Agency, had up to 5 consecutive days of 24-hour personal PM2.5 monitoring and daily cardiovascular (CV) measurements performed in their households during summer and/or winter periods. The associations between integrated hour-long total per...
Proof-Of-Concept Study For Precision Medicine With Chromosome Genomic Array Testing (CGAT) For Drug Sensitivity Screening In Acute Myeloid Leukemia
Authors: Min Fang, Scott McElhone, Xin Zhao, Barry E. Storer, Su-In Lee, C. Anthony Blau, Vivian G. Oehler, Elihu H. Estey, Frederick R. Appelbaum, Pamela S Becker
Journal: Blood (2013)