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Biophysical model-based parameters to classify tumor recurrence from radiation-induced necrosis for brain metastases.
Narasimhan S, Johnson HB, Nickles TM, Miga MI, Rana N, Attia A, Weis JA
(2019) Med Phys 46: 2487-2496
MeSH Terms: Brain Neoplasms, Humans, Magnetic Resonance Imaging, Models, Biological, Necrosis, Patient-Specific Modeling, Radiation Injuries, Radiosurgery, Recurrence, Retrospective Studies
Show Abstract · Added April 2, 2019
PURPOSE - Stereotactic radiosurgery (SRS) is used for local control treatment of patients with intracranial metastases. As a result of SRS, some patients develop radiation-induced necrosis. Radiographically, radiation-induced necrosis can appear similar to tumor recurrence in magnetic resonance (MR) T -weighted contrast-enhanced imaging, T -weighted MR imaging, and Fluid-Attenuated Inversion Recovery (FLAIR) MR imaging. Radiographic ambiguities often necessitate invasive brain biopsies to determine lesion etiology or cause delayed subsequent therapy initiation. We use a biomechanically coupled tumor growth model to estimate patient-specific model parameters and model-derived measures to noninvasively classify etiology of enhancing lesions in this patient population.
METHODS - In this initial, preliminary retrospective study, we evaluated five patients with tumor recurrence and five with radiation-induced necrosis. Longitudinal patient-specific MR imaging data were used in conjunction with the model to parameterize tumor cell proliferation rate and tumor cell diffusion coefficient, and Dice correlation coefficients were used to quantify degree of correlation between model-estimated mechanical stress fields and edema visualized from MR imaging.
RESULTS - Results found four statistically relevant parameters which can differentiate tumor recurrence and radiation-induced necrosis.
CONCLUSIONS - This preliminary investigation suggests potential of this framework to noninvasively determine the etiology of enhancing lesions in patients who previously underwent SRS for intracranial metastases.
© 2019 American Association of Physicists in Medicine.
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1 Members
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10 MeSH Terms
Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.
Poindexter SV, Reddy VK, Mittal MK, Williams AM, Washington MK, Harris E, Mah A, Hiebert SW, Singh K, Chaturvedi R, Wilson KT, Lund PK, Williams CS
(2015) Am J Physiol Gastrointest Liver Physiol 308: G562-71
MeSH Terms: Animals, Apoptosis, Cell Proliferation, Cell Survival, DNA Damage, Female, Gamma Rays, Gene Expression Regulation, Goblet Cells, Histones, Intestinal Mucosa, Intestine, Small, Male, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, Phenotype, Radiation Injuries, Experimental, Radiation Tolerance, Regeneration, Signal Transduction, Stem Cells, Tissue Culture Techniques, Transcription Factors, Wnt3A Protein
Show Abstract · Added January 20, 2015
Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.
1 Communities
5 Members
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25 MeSH Terms
Approaches to enhancing radiation safety in cardiovascular imaging: a scientific statement from the American Heart Association.
Fazel R, Gerber TC, Balter S, Brenner DJ, Carr JJ, Cerqueira MD, Chen J, Einstein AJ, Krumholz HM, Mahesh M, McCollough CH, Min JK, Morin RL, Nallamothu BK, Nasir K, Redberg RF, Shaw LJ, American Heart Association Council on Quality of Care and Outcomes Research, Council on Clinical Cardiology, and Council on Cardiovascular Radiology and Intervention
(2014) Circulation 130: 1730-48
MeSH Terms: American Heart Association, Cardiology, Cardiovascular Diseases, Education, Medical, Humans, Radiation Dosage, Radiation Injuries, Radiography, United States
Show Abstract · Added August 24, 2015
Education, justification, and optimization are the cornerstones to enhancing the radiation safety of medical imaging. Education regarding the benefits and risks of imaging and the principles of radiation safety is required for all clinicians in order for them to be able to use imaging optimally. Empowering patients with knowledge of the benefits and risks of imaging will facilitate their meaningful participation in decisions related to their health care, which is necessary to achieve patient-centered care. Limiting the use of imaging to appropriate clinical indications can ensure that the benefits of imaging outweigh any potential risks. Finally, the continually expanding repertoire of techniques that allow high-quality imaging with lower radiation exposure should be used when available to achieve safer imaging. The implementation of these strategies in practice is necessary to achieve high-quality, patient-centered imaging and will require a shared effort and investment by all stakeholders, including physicians, patients, national scientific and educational organizations, politicians, and industry.
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9 MeSH Terms
Outcomes of serial dilation for high-grade radiation-related esophageal strictures in head and neck cancer patients.
Francis DO, Hall E, Dang JH, Vlacich GR, Netterville JL, Vaezi MF
(2015) Laryngoscope 125: 856-62
MeSH Terms: Adult, Aged, Analysis of Variance, Carcinoma, Squamous Cell, Cohort Studies, Dilatation, Esophageal Stenosis, Esophagoscopy, Female, Follow-Up Studies, Head and Neck Neoplasms, Humans, Male, Middle Aged, Radiation Injuries, Radiotherapy Dosage, Recovery of Function, Retrospective Studies, Risk Assessment, Severity of Illness Index, Treatment Outcome
Show Abstract · Added September 28, 2015
OBJECTIVES/HYPOTHESIS - Dysphagia and esophageal stricture are frequent consequences of treatment for head and neck cancer. This study examines the effectiveness of the anterograde-retrograde rendezvous procedure and serial dilations in reestablishing esophageal patency to allow return to oral diet and gastrostomy tube removal in a cohort of patients with complete or near-complete esophageal stricture following nonsurgical cancer treatment.
STUDY DESIGN - Retrospective review of patients treated with radiation therapy with or without concurrent chemotherapy presented with complete or near-complete esophageal stricture. Patients underwent serial dilations using combined anterograde-retrograde dilation (rendezvous) techniques.
METHODS - Medical records of patients having undergone treatment between 2006 and 2012 were reviewed, and semistructured interviews were also conducted to determine current swallowing function and actual patient experience. The primary outcome was swallowing improvement that allowed for return to oral diet and/or gastrostomy tube removal. Outcomes were compared between patients with complete and near-complete (<5 mm in diameter) strictures and univariate analysis performed to identify associations between patient, cancer, and treatment characteristics on odds of gastrostomy tube removal.
RESULTS - Twenty-four patients (median age 59.5 years, 63% male, 91% Caucasian) underwent treatment. Fifty percent of patients had complete occlusion of the esophageal lumen. The majority of patients (92%) underwent either anterograde (54%) or combined antero-retrograde (38%) approach. Following a median (interquartile range) of 9 (6-20) dilation sessions, 42% of patients were able to return to an oral diet and/or had their gastrostomy tube removed. This outcome was independent of whether the stricture was complete or near complete (P = .67). Of patients who had their gastrostomy tubes removed, only 33.3% had ever smoked, compared to 92.3% of those whose tubes were not discharged (P = .007).
CONCLUSIONS - Recannulation is possible even in cases of complete or near-complete stricture. Several factors appear to impact the likelihood of successful outcome, but in this study, only patients with a history of smoking had a significantly lower likelihood of return to full oral diet.
© 2014 The American Laryngological, Rhinological and Otological Society, Inc.
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21 MeSH Terms
Patient-centered imaging: shared decision making for cardiac imaging procedures with exposure to ionizing radiation.
Einstein AJ, Berman DS, Min JK, Hendel RC, Gerber TC, Carr JJ, Cerqueira MD, Cullom SJ, DeKemp R, Dickert NW, Dorbala S, Fazel R, Garcia EV, Gibbons RJ, Halliburton SS, Hausleiter J, Heller GV, Jerome S, Lesser JR, Raff GL, Tilkemeier P, Williams KA, Shaw LJ
(2014) J Am Coll Cardiol 63: 1480-9
MeSH Terms: Cardiology, Cardiovascular Diseases, Decision Making, Diagnostic Imaging, Humans, Patient-Centered Care, Radiation Dosage, Radiation Injuries, Radiation, Ionizing
Show Abstract · Added February 28, 2014
The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3 mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20 mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization.
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
1 Communities
1 Members
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9 MeSH Terms
Uncertainties in estimating health risks associated with exposure to ionising radiation.
Preston RJ, Boice JD, Brill AB, Chakraborty R, Conolly R, Hoffman FO, Hornung RW, Kocher DC, Land CE, Shore RE, Woloschak GE
(2013) J Radiol Prot 33: 573-88
MeSH Terms: Animals, Animals, Laboratory, Dose-Response Relationship, Radiation, Environmental Exposure, Humans, Occupational Exposure, Photons, Radiation Dosage, Radiation Injuries, Radiation Protection, Radiation, Ionizing, Radiologic Health, Radon, Risk Assessment, Uncertainty, United States, United States National Aeronautics and Space Administration
Show Abstract · Added March 7, 2014
The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.
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17 MeSH Terms
Radiological protection issues arising during and after the Fukushima nuclear reactor accident.
González AJ, Akashi M, Boice JD, Chino M, Homma T, Ishigure N, Kai M, Kusumi S, Lee JK, Menzel HG, Niwa O, Sakai K, Weiss W, Yamashita S, Yonekura Y
(2013) J Radiol Prot 33: 497-571
MeSH Terms: Child, Earthquakes, Environmental Exposure, Female, Fukushima Nuclear Accident, Humans, Incidence, Infant, Japan, Nuclear Power Plants, Pregnancy, Radiation Dosage, Radiation Injuries, Radiation Monitoring, Radiation Protection, Radioactive Fallout, Rescue Work, Risk Assessment, Risk Factors
Show Abstract · Added March 7, 2014
Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.
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19 MeSH Terms
A novel radioprotective function for the mitochondrial tumor suppressor protein Fus1.
Yazlovitskaya EM, Uzhachenko R, Voziyan PA, Yarbrough WG, Ivanova AV
(2013) Cell Death Dis 4: e687
MeSH Terms: Animals, Apoptosis, Cell Proliferation, Female, Intestinal Mucosa, Intestine, Small, Mice, Mice, Knockout, Mitosis, Radiation Injuries, Experimental, Radiation Tolerance, Signal Transduction, Tumor Suppressor Proteins, Whole-Body Irradiation
Show Abstract · Added August 21, 2013
FUS1/TUSC2 is a mitochondrial tumor suppressor with activity to regulate cellular oxidative stress by maintaining balanced ROS production and mitochondrial homeostasis. Fus1 expression is inhibited by ROS, suggesting that individuals with a high level of ROS may have lower Fus1 in normal tissues and, thus, may be more prone to oxidative stress-induced side effects of cancer treatment, including radiotherapy. As the role of Fus1 in the modulation of cellular radiosensitivity is unknown, we set out to determine molecular mechanisms of Fus1 involvement in the IR response in normal tissues. Mouse whole-body irradiation methodology was employed to determine the role for Fus1 in the radiation response and explore underlying molecular mechanisms. Fus1(-/-) mice were more susceptible to radiation compared with Fus1(+/+) mice, exhibiting increased mortality and accelerated apoptosis of the GI crypt epithelial cells. Following untimely reentrance into the cell cycle, the Fus1(-/-) GI crypt cells died at accelerated rate via mitotic catastrophe that resulted in diminished and/or delayed crypt regeneration after irradiation. At the molecular level, dysregulated dynamics of activation of main IR response proteins (p53, NFκB, and GSK-3β), as well as key signaling pathways involved in oxidative stress response (SOD2, PRDX1, and cytochrome c), apoptosis (BAX and PARP1), cell cycle (Cyclins B1 and D1), and DNA repair (γH2AX) were found in Fus1(-/-) cells after irradiation. Increased radiosensitivity of other tissues, such as immune cells and hair follicles was also detected in Fus1(-/-) mice. Our findings demonstrate a previously unknown radioprotective function of the mitochondrial tumor suppressor Fus1 in normal tissues and suggest new individualized therapeutic approaches based on Fus1 expression.
1 Communities
2 Members
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14 MeSH Terms
Cardiovascular complications of radiation therapy for thoracic malignancies: the role for non-invasive imaging for detection of cardiovascular disease.
Groarke JD, Nguyen PL, Nohria A, Ferrari R, Cheng S, Moslehi J
(2014) Eur Heart J 35: 612-23
MeSH Terms: Diagnostic Imaging, Heart Diseases, Humans, Patient Care Planning, Preoperative Care, Radiation Dosage, Radiation Injuries, Thoracic Neoplasms, Vascular Diseases
Show Abstract · Added March 4, 2015
Radiation exposure to the thorax is associated with substantial risk for the subsequent development of cardiovascular disease. Thus, the increasing role of radiation therapy in the contemporary treatment of cancer, combined with improving survival rates of patients undergoing this therapy, contributes to a growing population at risk of cardiovascular morbidity and mortality. Associated cardiovascular injuries include pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy, and medium and large vessel vasculopathy-any of which can occur at varying intervals following irradiation. Higher radiation doses, younger age at the time of irradiation, longer intervals from the time of radiation, and coexisting cardiovascular risk factors all predispose to these injuries. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multicentre studies with a sufficient duration of cardiovascular follow-up. There are currently no consensus guidelines available to inform the optimal approach to cardiovascular surveillance of recipients of thoracic radiation. Therefore, we review the cardiovascular consequences of radiation therapy and focus on the potential role of non-invasive cardiovascular imaging in the assessment and management of radiation-related cardiovascular disease. In doing so, we highlight characteristics that can be used to identify individuals at risk for developing post-radiation cardiovascular disease and propose an imaging-based algorithm for their clinical surveillance.
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9 MeSH Terms
The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study.
Kent ST, Kabagambe EK, Wadley VG, Howard VJ, Crosson WL, Al-Hamdan MZ, Judd SE, Peace F, McClure LA
(2014) Int J Biometeorol 58: 361-70
MeSH Terms: African Continental Ancestry Group, Age Distribution, Aged, Aged, 80 and over, Climate, Cognition Disorders, Environmental Exposure, European Continental Ancestry Group, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Radiation Dosage, Radiation Injuries, Radiation Monitoring, Risk Factors, Sex Distribution, Solar Energy, Sunlight, Temperature, United States, Weather
Show Abstract · Added March 7, 2014
Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.
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24 MeSH Terms