The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

PubMed

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The Dose Effects of Short-Term Dronabinol (Oral THC) Maintenance in Daily Cannabis Users

PubMed Central

Vandrey, Ryan; Stitzer, Maxine L.; Mintzer, Miriam Z.; Huestis, Marilyn A.; Murray, Jeannie A.; Lee, Dayong

2012-01-01

BACKGROUND Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked 5 puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad-libitum cannabis use. RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses. CONCLUSIONS Dronabinol’s ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg per day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. PMID:22921474

Evaluation of radiation dose of triple rule-out coronary angiography protocols with different scan length using 256-slice CT

NASA Astrophysics Data System (ADS)

Tsai, Chia-Jung; Lee, Jason J. S.; Chen, Liang-Kuang; Mok, Greta S. P.; Hsu, Shih-Ming; Wu, Tung-Hsin

2011-10-01

Triple rule-out coronary CT angiography (TRO-CTA) is a new approach for providing noninvasive visualization of coronary arteries with simultaneous evaluation of pulmonary arteries, thoracic aorta and other intrathoracic structures. The increasing use of TRO-CTA examination with longer scan length is associated with the concerns about radiation dose and their corresponding cancer risk. The purpose of this study is to evaluate organ dose and effective dose for the TRO-CTA examination with 2 scan lengths: TRO std and TRO ext, using 256-slice CT. TRO-CTA examinations were performed on a 256-slice CT scanner without ECG-based tube current modulation. Absorbed organ doses were measured using an anthropomorphic phantom and thermal-luminance dosimeters (TLDs). Effective dose was determined by taking a sum of the measured absorbed organ doses multiplied with the tissue weighting factor based on ICRP-103, and compared to that calculated using the dose-length product (DLP) method. We obtained high organ doses in the thyroid, esophagus, breast, heart and lung in both TRO-CTA protocols. Effective doses of the TRO std and TRO ext protocols with the phantom method were 26.37 and 42.49 mSv, while those with the DLP method were 19.68 and 38.96 mSv, respectively. Our quantitative dose information establishes a relationship between radiation dose and scanning length, and can provide a practical guidance to best clinical practice.

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Iatrogenic radiation exposure to patients with early onset spine and chest wall deformities.

PubMed

Khorsand, Derek; Song, Kit M; Swanson, Jonathan; Alessio, Adam; Redding, Gregory; Waldhausen, John

2013-08-01

Retrospective cohort series. Characterize average iatrogenic radiation dose to a cohort of children with thoracic insufficiency syndrome (TIS) during assessment and treatment at a single center with vertically expandable prosthetic titanium rib. Children with TIS undergo extensive evaluations to characterize their deformity. No standardized radiographical evaluation exists, but all reports use extensive imaging. The source and level of radiation these patients receive is not currently known. We evaluated a retrospective consecutive cohort of 62 children who had surgical treatment of TIS at our center from 2001-2011. Typical care included obtaining serial radiographs, spine and chest computed tomographic (CT) scans, ventilation/perfusion scans, and magnetic resonance images. Epochs of treatment were divided into time of initial evaluation to the end of initial vertically expandable prosthetic titanium rib implantation with each subsequent epoch delineated by the next surgical intervention. The effective dose for each examination was estimated within millisieverts (mSv). Plain radiographs were calculated from references. Effective dose was directly estimated for CT scans since 2007 and an average of effective dose from 2007-2011 was used for scans before 2007. Effective dose from fluoroscopy was directly estimated. All doses were reported in mSv. A cohort of 62 children had a total of 447 procedures. There were a total of 290 CT scans, 4293 radiographs, 147 magnetic resonance images, and 134 ventilation/perfusion scans. The average accumulated effective dose was 59.6 mSv for children who had completed all treatment, 13.0 mSv up to initial surgery, and 3.2 mSv for each subsequent epoch of treatment. CT scans accounted for 74% of total radiation dose. Children managed for TIS using a consistent protocol received iatrogenic radiation doses that were on average 4 times the estimated average US background radiation exposure of 3 mSv/yr. CT scans comprised 74% of the total dose. 3.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies.

PubMed

Silva-Rodríguez, Jesús; Aguiar, Pablo; Sánchez, Manuel; Mosquera, Javier; Luna-Vega, Víctor; Cortés, Julia; Garrido, Miguel; Pombar, Miguel; Ruibal, Alvaro

2014-05-01

Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva-Rodríguez, Jesús, E-mail: jesus.silva.rodriguez@sergas.es; Aguiar, Pablo, E-mail: pablo.aguiar.fernandez@sergas.es; Servicio de Medicina Nuclear, Complexo Hospitalario Universidade de Santiago de Compostela

Purpose: Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. Methods: One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manualmore » ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Results: Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. Conclusions: The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.« less

A Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray.

PubMed

Sellers, Edward M; Schoedel, Kerri; Bartlett, Cindy; Romach, Myroslava; Russo, Ethan B; Stott, Colin G; Wright, Stephen; White, Linda; Duncombe, Paul; Chen, Chien-Feng

2013-07-01

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies. © The Author(s) 2013.

Abdominal Pediatric Cancer Surveillance using Serial CT: Evaluation of Organ Absorbed Dose and Effective Dose

PubMed Central

Lam, Diana; Wootton-Gorges, Sandra L.; McGahan, John P.; Stern, Robin; Boone, John M.

2012-01-01

Computed tomography (CT) is used extensively in cancer diagnosis, staging, evaluation of response to treatment, and in active surveillance for cancer reoccurrence. A review of CT technology is provided, at a level of detail appropriate for a busy clinician to review. The basis of x-ray CT dosimetry is also discussed, and concepts of absorbed dose and effective dose are distinguished. Absorbed dose is a physical quantity (measured in milliGray) equal to the x-ray energy deposited in a mass of tissue, whereas effective dose utilizes an organ-specific weighting method which converts organ doses to effective dose measured in milliSieverts. The organ weighting values carry with them a measure of radiation risk, and so effective dose (in mSv) is not a physical dose metric but rather is one that conveys radiation risk. The use of CT in a cancer surveillance protocol was used as an example of a pediatric patient who had kidney cancer, with surgery and radiation therapy. The active use of CT for cancer surveillance along with diagnostic CT scans led to a total of 50 CT scans performed on this child in a 7 year period. It was estimated that the patient received an average organ dose of 431 mGy from these CT scans. By comparison, the radiation therapy was performed and delivered 50.4 Gy to the patient’s abdomen. Thus, the total dose from CT represented only 0.8% of the patients radiation dose. PMID:21362521

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

PubMed

Marshall, I; Bianchi, M

1983-08-01

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

Low-dose vaporized cannabis significantly improves neuropathic pain.

PubMed

Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

Verification of the grid size and angular increment effects in lung stereotactic body radiation therapy using the dynamic conformal arc technique

NASA Astrophysics Data System (ADS)

Park, Hae-Jin; Suh, Tae-Suk; Park, Ji-Yeon; Lee, Jeong-Woo; Kim, Mi-Hwa; Oh, Young-Taek; Chun, Mison; Noh, O. Kyu; Suh, Susie

2013-06-01

The dosimetric effects of variable grid size and angular increment were systematically evaluated in the measured dose distributions of dynamic conformal arc therapy (DCAT) for lung stereotactic body radiation therapy (SBRT). Dose variations with different grid sizes (2, 3, and 4 mm) and angular increments (2, 4, 6, and 10°) for spherical planning target volumes (PTVs) were verified in a thorax phantom by using EBT2 films. Although the doses for identical PTVs were predicted for the different grid sizes, the dose discrepancy was evaluated using one measured dose distribution with the gamma tool because the beam was delivered in the same set-up for DCAT. The dosimetric effect of the angular increment was verified by comparing the measured dose area histograms of organs at risk (OARs) at each angular increment. When the difference in the OAR doses is higher than the uncertainty of the film dosimetry, the error is regarded as the angular increment effect in discretely calculated doses. In the results, even when a 2-mm grid size was used with an elaborate dose calculation, 4-mm grid size led to a higher gamma pass ratio due to underdosage, a steep-dose descent gradient, and lower estimated PTV doses caused by the smoothing effect in the calculated dose distribution. An undulating dose distribution and a difference in the maximum contralateral lung dose of up to 14% were observed in dose calculation using a 10° angular increment. The DCAT can be effectively applied for an approximately spherical PTV in a relatively uniform geometry, which is less affected by inhomogeneous materials and differences in the beam path length.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

Reproductive effects of lipid soluble components of Syzygium aromaticum flower bud in male mice

PubMed Central

Mishra, Raghav Kumar; Singh, Shio Kumar

2013-01-01

Background: The flower buds of Syzygium aromaticum (clove) have been used in indigenous medicines for the treatment of male sexual disorders in Indian subcontinent. Objective: To evaluate the effect of Syzygium aromaticum flower bud on male reproduction, using Parkes (P) strain mice as animal model. Materials and Methods: Mice were orally administered lipid soluble components of Syzygium aromaticum flower bud in doses of 15, 30, and 60 mg/kg body weight for 35 days, and several male reproductive endpoints were evaluated. Results: Treatment with lower dose (15 mg) of Syzygium increased the motility of sperm and stimulated the secretory activities of epididymis and seminal vesicle, while higher doses (30 and 60 mg) had adverse effects on sperm dynamics of cauda epididymidis and on the secretory activities of epididymis and seminal vesicle. Libido was not affected in treated males; however, a significant decrease in litter in females sired by males treated with higher doses of Syzygium was recorded. Conclusion: Treatment with Syzygium aromaticum flower bud causes dose-dependent biphasic effect on male reproductive indices in P mice; lower dose of Syzygium appears stimulatory, while the higher doses have adverse effect on male reproduction. The results suggest that the lower dose of Syzygium may have androgenic effect, but further studies are needed to support this contention. PMID:23930041

Combined effects of gamma radiation doses and sodium nitrite content on the lipid oxidation and color of mortadella.

PubMed

Dutra, Monalisa Pereira; Cardoso, Giselle Pereira; Fontes, Paulo Rogério; Silva, Douglas Roberto Guimarães; Pereira, Marcio Tadeu; Ramos, Alcinéia de Lemos Souza; Ramos, Eduardo Mendes

2017-12-15

The effects of different doses of gamma radiation (0-20kGy) on the color and lipid oxidation of mortadella prepared with increasing nitrite levels (0-300ppm) were evaluated using a central composite rotatable design. Higher radiation doses increased the redox potential, promoted the lipid oxidation and elevating the hue color of the mortadellas. Nevertheless, higher addition of sodium nitrite elevated the residual nitrite content, reduced the lipid oxidation and promoted the increase of redness and the reduce of hue color of the mortadellas, regardless of the radiation dose applied. Nitrite addition had a greater effect than irradiation on the quality parameters evaluated, and even at low levels (∼75ppm), its use decreased the deleterious effects of irradiation at doses as high as 20kGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging the Parasinus Region with a Third-Generation Dual-Source CT and the Effect of Tin Filtration on Image Quality and Radiation Dose.

PubMed

Lell, M M; May, M S; Brand, M; Eller, A; Buder, T; Hofmann, E; Uder, M; Wuest, W

2015-07-01

CT is the imaging technique of choice in the evaluation of midface trauma or inflammatory disease. We performed a systematic evaluation of scan protocols to optimize image quality and radiation exposure on third-generation dual-source CT. CT protocols with different tube voltage (70-150 kV), current (25-300 reference mAs), prefiltration, pitch value, and rotation time were systematically evaluated. All images were reconstructed with iterative reconstruction (Advanced Modeled Iterative Reconstruction, level 2). To individually compare results with otherwise identical factors, we obtained all scans on a frozen human head. Conebeam CT was performed for image quality and dose comparison with multidetector row CT. Delineation of important anatomic structures and incidental pathologic conditions in the cadaver head was evaluated. One hundred kilovolts with tin prefiltration demonstrated the best compromise between dose and image quality. The most dose-effective combination for trauma imaging was Sn100 kV/250 mAs (volume CT dose index, 2.02 mGy), and for preoperative sinus surgery planning, Sn100 kV/150 mAs (volume CT dose index, 1.22 mGy). "Sn" indicates an additional prefiltration of the x-ray beam with a tin filter to constrict the energy spectrum. Exclusion of sinonasal disease was possible with even a lower dose by using Sn100 kV/25 mAs (volume CT dose index, 0.2 mGy). High image quality at very low dose levels can be achieved by using a Sn100-kV protocol with iterative reconstruction. The effective dose is comparable with that of conventional radiography, and the high image quality at even lower radiation exposure favors multidetector row CT over conebeam CT. © 2015 by American Journal of Neuroradiology.

Evaluation of World Population-Weighted Effective Dose due to Cosmic Ray Exposure

PubMed Central

Sato, Tatsuhiko

2016-01-01

After the release of the Report of the United Nations Scientific Committee of the Effects of Atomic Radiation in 2000 (UNSCEAR2000), it became commonly accepted that the world population-weighted effective dose due to cosmic-ray exposure is 0.38 mSv, with a range from 0.3 to 2 mSv. However, these values were derived from approximate projections of altitude and geographic dependences of the cosmic-ray dose rates as well as the world population. This study hence re-evaluated the population-weighted annual effective doses and their probability densities for the entire world as well as for 230 individual nations, using a sophisticated cosmic-ray flux calculation model in tandem with detailed grid population and elevation databases. The resulting world population-weighted annual effective dose was determined to be 0.32 mSv, which is smaller than the UNSCEAR’s evaluation by 16%, with a range from 0.23 to 0.70 mSv covering 99% of the world population. These values were noted to vary with the solar modulation condition within a range of approximately 15%. All assessed population-weighted annual effective doses as well as their statistical information for each nation are provided in the supplementary files annexed to this report. These data improve our understanding of cosmic-ray radiation exposures to populations globally. PMID:27650664

A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

PubMed

Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

2015-10-01

This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Dosimetric evaluation of a MOSFET detector for clinical application in photon therapy.

PubMed

Kohno, Ryosuke; Hirano, Eriko; Nishio, Teiji; Miyagishi, Tomoko; Goka, Tomonori; Kawashima, Mitsuhiko; Ogino, Takashi

2008-01-01

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

Dedicated dental volumetric and total body multislice computed tomography: a comparison of image quality and radiation dose

NASA Astrophysics Data System (ADS)

Strocchi, Sabina; Colli, Vittoria; Novario, Raffaele; Carrafiello, Gianpaolo; Giorgianni, Andrea; Macchi, Aldo; Fugazzola, Carlo; Conte, Leopoldo

2007-03-01

Aim of this work is to compare the performances of a Xoran Technologies i-CAT Cone Beam CT for dental applications with those of a standard total body multislice CT (Toshiba Aquilion 64 multislice) used for dental examinations. Image quality and doses to patients have been compared for the three main i-CAT protocols, the Toshiba standard protocol and a Toshiba modified protocol. Images of two phantoms have been acquired: a standard CT quality control phantom and an Alderson Rando ® anthropomorphic phantom. Image noise, Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR) and geometric accuracy have been considered. Clinical image quality was assessed. Effective dose and doses to main head and neck organs were evaluated by means of thermo-luminescent dosimeters (TLD-100) placed in the anthropomorphic phantom. A Quality Index (QI), defined as the ratio of squared CNR to effective dose, has been evaluated. The evaluated effective doses range from 0.06 mSv (i-CAT 10 s protocol) to 2.37 mSv (Toshiba standard protocol). The Toshiba modified protocol (halved tube current, higher pitch value) imparts lower effective dose (0.99 mSv). The conventional CT device provides lower image noise and better SNR, but clinical effectiveness similar to that of dedicated dental CT (comparable CNR and clinical judgment). Consequently, QI values are much higher for this second CT scanner. No geometric distortion has been observed with both devices. As a conclusion, dental volumetric CT supplies adequate image quality to clinical purposes, at doses that are really lower than those imparted by a conventional CT device.

Preclinical toxicity profile of oral bilastine.

PubMed

Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

2012-06-01

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Evaluation of the medical exposure doses regarding dental examinations with different X-ray instruments

NASA Astrophysics Data System (ADS)

Liu, Yi-Chi; Chuang, Keh-Shih; Yu, Cheng-Ching; Chao, Jiunn-Hsing; Hsu, Fang-Yuh

2015-11-01

Modern dental X-ray examination that consists of traditional form, panorama, and cone-beamed 3D technologies is one of the most frequent diagnostic applications nowadays. This study used the Rando Phantom and thermoluminescence dosimeters (TLD) to measure the absorbed doses of radiosensitive organs recommended by International Commission on Radiological Protection (ICRP), and whole body effective doses which were delivered due to dental X-ray examination performed with different types of X-ray instrument. Besides, enamel samples which performed reading with Electronic Paramagnetic Resonance (EPR) procedure were also used to estimate the tooth doses. EPR is a dose reconstruction method of measuring free radicals induced by radiation exposure to the calcified tissue (mainly in the tooth enamel or bone) to evaluate the accepted high dose. The tooth doses estimated by TLD and EPR methods were compared. Relationships between the tooth doses and effective doses by dental X-ray examinations with different types of X-ray equipment were investigated in this work.

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification.

PubMed

Palmer, Antony L; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H

2015-11-21

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification

NASA Astrophysics Data System (ADS)

Palmer, Antony L.; Dimitriadis, Alexis; Nisbet, Andrew; Clark, Catharine H.

2015-11-01

There is renewed interest in film dosimetry for the verification of dose delivery of complex treatments, particularly small fields, compared to treatment planning system calculations. A new radiochromic film, Gafchromic EBT-XD, is available for high-dose treatment verification and we present the first published evaluation of its use. We evaluate the new film for MV photon dosimetry, including calibration curves, performance with single- and triple-channel dosimetry, and comparison to existing EBT3 film. In the verification of a typical 25 Gy stereotactic radiotherapy (SRS) treatment, compared to TPS planned dose distribution, excellent agreement was seen with EBT-XD using triple-channel dosimetry, in isodose overlay, maximum 1.0 mm difference over 200-2400 cGy, and gamma evaluation, mean passing rate 97% at 3% locally-normalised, 1.5 mm criteria. In comparison to EBT3, EBT-XD gave improved evaluation results for the SRS-plan, had improved calibration curve gradients at high doses, and had reduced lateral scanner effect. The dimensions of the two films are identical. The optical density of EBT-XD is lower than EBT3 for the same dose. The effective atomic number for both may be considered water-equivalent in MV radiotherapy. We have validated the use of EBT-XD for high-dose, small-field radiotherapy, for routine QC and a forthcoming multi-centre SRS dosimetry intercomparison.

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

PubMed Central

García-Gea, Consuelo; Ballester, Maria Rosa; Martínez, Juan; Antonijoan, Rosa Maria; Donado, Esther; Izquierdo, Iñaki; Barbanoj, Manuel-José

2010-01-01

AIM The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H1-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg. METHODS Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg. RESULTS Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated. CONCLUSION Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations. PMID:20565458

Effects of atrazine (ATR), deisopropylatrazine (DIA), Diaminochlorotriazine (DACT) on the hypothalamic-pituitary-adrenal (HPA) axis in female rats

EPA Science Inventory

We previously reported that a single dose of the herbicide ATR stimulated the HPA axis in the male rat while equimolar doses of its primary metabolite, DACT, had a minimal effect. In this study, we evaluated the effects of one or four daily doses of ATR, DACT, and an intermediat...

Evaluation of the effective dose during BNCT at TRR thermal column epithermal facility.

PubMed

Jarahi, Hossein; Kasesaz, Yaser; Saleh-Koutahi, Seyed Mohsen

2016-04-01

An epithermal neutron beam has been designed for Boron neutron Capture Therapy (BNCT) at the thermal column of Tehran Research Reactor (TRR) recently. In this paper the whole body effective dose, as well as the equivalent doses of several organs have been calculated in this facility using MCNP4C Monte Carlo code. The effective dose has been calculated by using the absorbed doses determined for each individual organ, taking into account the radiation and tissue weighting factors. The ICRP 110 whole body male phantom has been used as a patient model. It was found that the effective dose during BNCT of a brain tumor is equal to 0.90Sv. This effective dose may induce a 4% secondary cancer risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calculation of Dose, Dose Equivalent, and Relative Biological Effectiveness for High Charge and Energy Ion Beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Reginatto, M.; Hajnal, F.; Chun, S. Y.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H1OT1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications.

Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Chun, S. Y.; Reginatto, M.; Hajnal, F.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neo-plastic transformation as function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical application.

Optimal dose selection of N-methyl-N-nitrosourea for the rat comet assay to evaluate DNA damage in organs with different susceptibility to cytotoxicity.

PubMed

Kitamoto, Sachiko; Matsuyama, Ryoko; Uematsu, Yasuaki; Ogata, Keiko; Ota, Mika; Yamada, Toru; Miyata, Kaori; Funabashi, Hitoshi; Saito, Koichi

2015-07-01

The in vivo rodent alkaline comet assay (comet assay) is a promising technique to evaluate DNA damage in vivo. However, there is no agreement on a method to evaluate DNA damage in organs where cytotoxicity is observed. As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the comet assay, we examined DNA damage in the liver, stomach, and bone marrow of rats given three oral doses of N-methyl-N-nitrosourea (MNU) up to the maximum tolerated dose based on systemic toxicity. MNU significantly increased the % tail DNA in all the organs. Histopathological analysis showed no cytotoxic effect on the liver, indicating clearly that MNU has a genotoxic potential in the liver. In the stomach, however, the cytotoxic effects were very severe at systemically non-toxic doses. Low-dose MNU significantly increased the % tail DNA even at a non-cytotoxic dose, indicating that MNU has a genotoxic potential also in the stomach. Part of the DNA damage at cytotoxic doses was considered to be a secondary effect of severe cell damage. In the bone marrow, both the % tail DNA and incidence of micronucleated polychromatic erythrocytes significantly increased at non-hematotoxic doses, which were different from the non-cytotoxic doses for liver and stomach. These findings indicate that an optimal dose for detecting DNA damage may vary among organs and that careful attention is required to select an optimum dose for the comet assay based on systemic toxicity such as mortality and clinical observations. The present study shows that when serious cytotoxicity is suggested by increased % hedgehogs in the comet assay, histopathological examination should be included for the evaluation of a positive response. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis.

PubMed

Abdel Shaheed, Christina; Maher, Chris G; Williams, Kylie A; Day, Richard; McLachlan, Andrew J

2016-07-01

Opioid analgesics are commonly used for low back pain, however, to our knowledge there has been no systematic evaluation of the effect of opioid dose and use of enrichment study design on estimates of treatment effect. To evaluate efficacy and tolerability of opioids in the management of back pain; and investigate the effect of opioid dose and use of an enrichment study design on treatment effect. Medline, EMBASE, CENTRAL, CINAHL, and PsycINFO (inception to September 2015) with citation tracking from eligible randomized clinical trials (RCTs). Placebo-controlled RCTs in any language. Two authors independently extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The primary outcome measure was pain. Pain and disability outcomes were converted to a common 0 to 100 scale, with effects greater than 20 points considered clinically important. Of 20 included RCTs of opioid analgesics (with a total of 7925 participants), 13 trials (3419 participants) evaluated short-term effects on chronic low back pain, and no placebo-controlled trials enrolled patients with acute low back pain. In half of these 13 trials, at least 50% of participants withdrew owing to adverse events or lack of efficacy. There was moderate-quality evidence that opioid analgesics reduce pain in the short term; mean difference (MD), -10.1 (95% CI, -12.8 to -7.4). Meta-regression revealed a 12.0 point greater pain relief for every 1 log unit increase in morphine equivalent dose (P = .046). Clinically important pain relief was not observed within the dose range evaluated (40.0-240.0-mg morphine equivalents per day). There was no significant effect of enrichment study design. For people with chronic low back pain who tolerate the medicine, opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important within guideline recommended doses. Evidence on long-term efficacy is lacking. The efficacy of opioid analgesics in acute low back pain is unknown.

Evaluation of annual committed effective doses to members of the public in Morocco due to 238U and 232Th in various food materials.

PubMed

Misdaq, M A; Bourzik, W

2004-12-01

Uranium (238U) and thorium (232Th) concentrations were measured in different foods widely consumed in Morocco by using CR-39 and LR-115 type II solid state nuclear track detectors (SSNTDs). Annual committed effective doses due to 238U and 232Th intakes from the ingestion of the studied food materials were evaluated for different age groups of individuals, using the ICRP ingestion dose coefficients. The influence of the 238U and 232Th intakes and ages of individuals on the committed effective dose was investigated. Total annual intakes of 238U and 232Th for a typical food basket for adult members of the Moroccan population were estimated to be 451 +/- 27 Bq y(-1) and 359 +/- 20 Bq y(-1), corresponding to committed effective doses of (20 +/- 1) x 10(-6) Sv y(-1) and (83 +/- 5) x 10(-6) Sv y(-1), respectively.

Ambient dose equivalent and effective dose from scattered x-ray spectra in mammography for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations.

PubMed

Künzel, R; Herdade, S B; Costa, P R; Terini, R A; Levenhagen, R S

2006-04-21

In this study, scattered x-ray distributions were produced by irradiating a tissue equivalent phantom under clinical mammographic conditions by using Mo/Mo, Mo/Rh and W/Rh anode/filter combinations, for 25 and 30 kV tube voltages. Energy spectra of the scattered x-rays have been measured with a Cd(0.9)Zn(0.1)Te (CZT) detector for scattering angles between 30 degrees and 165 degrees . Measurement and correction processes have been evaluated through the comparison between the values of the half-value layer (HVL) and air kerma calculated from the corrected spectra and measured with an ionization chamber in a nonclinical x-ray system with a W/Mo anode/filter combination. The shape of the corrected x-ray spectra measured in the nonclinical system was also compared with those calculated using semi-empirical models published in the literature. Scattered x-ray spectra measured in the clinical x-ray system have been characterized through the calculation of HVL and mean photon energy. Values of the air kerma, ambient dose equivalent and effective dose have been evaluated through the corrected x-ray spectra. Mean conversion coefficients relating the air kerma to the ambient dose equivalent and to the effective dose from the scattered beams for Mo/Mo, Mo/Rh and W/Rh anode/filter combinations were also evaluated. Results show that for the scattered radiation beams the ambient dose equivalent provides an overestimate of the effective dose by a factor of about 5 in the mammography energy range. These results can be used in the control of the dose limits around a clinical unit and in the calculation of more realistic protective shielding barriers in mammography.

Evaluation and mitigation of the interplay effects for intensity modulated proton therapy for lung cancer in a clinical setting

PubMed Central

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y.; Liao, Li; Zhu, Ronald X.; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D.; Lim, Gino; Zhang, Xiaodong

2015-01-01

Purpose The primary aim of this study was to evaluate the impact of interplay effects for intensity-modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of iso-layered re-scanning for mitigating these interplay effects. Methods and Materials Single-fraction 4D dynamic dose without considering re-scanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on moving patient described by 4D computed tomography (4DCT) during the IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase corresponding to the life span of that spot, and the final dose was accumulated to a reference CT phase by using deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected. Results The CTV prescription coverage for the 7 patients were 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53%, calculated with use of the 4D composite dose, and were 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% with use of the 1FX dynamic dose. For the 7 patients, the CTV coverage, calculated by using single-fraction dynamic dose, were 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, using maximum MU limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. Conclusions Single-fraction 4D dynamic dose without re-scanning was validated as a surrogate to evaluate the interplay effects for IMPT for lung cancer in the clinical setting. The interplay effects can be potentially mitigated by increasing the number of iso-layered re-scanning in each fraction delivery. PMID:25407877

Evaluation and mitigation of the interplay effects of intensity modulated proton therapy for lung cancer in a clinical setting.

PubMed

Kardar, Laleh; Li, Yupeng; Li, Xiaoqiang; Li, Heng; Cao, Wenhua; Chang, Joe Y; Liao, Li; Zhu, Ronald X; Sahoo, Narayan; Gillin, Michael; Liao, Zhongxing; Komaki, Ritsuko; Cox, James D; Lim, Gino; Zhang, Xiaodong

2014-01-01

The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects. A single-fraction 4-dimensional (4D) dynamic dose without considering rescanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on a moving patient, described by 4D computed tomography during IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase that corresponded to the life span of that spot, and the final dose was accumulated to a reference computed tomography phase by use of deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected for study. The clinical target volume (CTV) prescription coverage for the 7 patients was 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53% when calculated with the 4D composite dose and 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% when calculated with the 1FX dynamic dose. For these 7 patients, the CTV coverage calculated by use of a single-fraction dynamic dose was 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, with a maximum monitor unit limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. A single-fraction 4D dynamic dose without rescanning was validated as a surrogate to evaluate the interplay effects of IMPT for lung cancer in the clinical setting. The interplay effects potentially can be mitigated by increasing the amount of isolayered rescanning in each fraction delivery.

Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

PubMed

Ahmad, Hesham M

2015-01-01

Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

Validation of a Preclinical Spinal Safety Model: Effects of Intrathecal Morphine in the Neonatal Rat

PubMed Central

Westin, B. David; Walker, Suellen M.; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L.

2010-01-01

Background Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long term function following intrathecal morphine in the neonatal rat. Methods Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P)3, 10 and 21. The relationship between injectate volume and segmental spread was assessed post mortem and by in-vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 minutes following intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis and glial response were evaluated 1 and 7 days following P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Results Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally-mediated analgesia at all ages with lower dose requirements in younger pups. High dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. Conclusions The therapeutic ratio for intrathecal morphine (toxic dose / antinociceptive dose) was at least 300 at P3, and at least 20 at P21 (latter doses limited by side effects). This data provides relative efficacy and safety data for comparison with other analgesic preparations and contributes supporting evidence for the validity of this preclinical neonatal safety model. PMID:20526189

Validation of a preclinical spinal safety model: effects of intrathecal morphine in the neonatal rat.

PubMed

Westin, B David; Walker, Suellen M; Deumens, Ronald; Grafe, Marjorie; Yaksh, Tony L

2010-07-01

Preclinical studies demonstrate increased neuroapoptosis after general anesthesia in early life. Neuraxial techniques may minimize potential risks, but there has been no systematic evaluation of spinal analgesic safety in developmental models. We aimed to validate a preclinical model for evaluating dose-dependent efficacy, spinal cord toxicity, and long-term function after intrathecal morphine in the neonatal rat. Lumbar intrathecal injections were performed in anesthetized rats aged postnatal day (P) 3, 10, and 21. The relationship between injectate volume and segmental spread was assessed postmortem and by in vivo imaging. To determine the antinociceptive dose, mechanical withdrawal thresholds were measured at baseline and 30 min after intrathecal morphine. To evaluate toxicity, doses up to the maximum tolerated were administered, and spinal cord histopathology, apoptosis, and glial response were evaluated 1 and 7 days after P3 or P21 injection. Sensory thresholds and gait analysis were evaluated at P35. Intrathecal injection can be reliably performed at all postnatal ages and injectate volume influences segmental spread. Intrathecal morphine produced spinally mediated analgesia at all ages with lower dose requirements in younger pups. High-dose intrathecal morphine did not produce signs of spinal cord toxicity or alter long-term function. The therapeutic ratio for intrathecal morphine (toxic dose/antinociceptive dose) was at least 300 at P3 and at least 20 at P21 (latter doses limited by side effects). These data provide relative efficacy and safety for comparison with other analgesic preparations and contribute supporting evidence for the validity of this preclinical neonatal safety model.

Cost Effectiveness of Genotype-Guided Warfarin Dosing in Patients with Mechanical Heart Valve Replacement Under the Fee-for-Service System.

PubMed

Kim, Dong-Jin; Kim, Ho-Sook; Oh, Minkyung; Kim, Eun-Young; Shin, Jae-Gook

2017-10-01

Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service (FFS) insurance system. The aim of this study was to evaluate the cost effectiveness of genotype-guided warfarin dosing in patients with MHVR under the FFS system from the Korea healthcare sector perspective. A decision-analytic Markov model was developed to evaluate the cost effectiveness of genotype-guided warfarin dosing compared with standard dosing. Estimates of clinical adverse event rates and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs than standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8) (year 2016 values). The ICER was US$1356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant compared with standard dosing, and a 99.8% probability that it was cost effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost effective in MHVR patients under the FFS insurance system.

Evaluating the risk of death via the hematopoietic syndrome mode for prolonged exposure of nuclear workers to radiation delivered at very low rates.

PubMed

Scott, B R; Lyzlov, A F; Osovets, S V

1998-05-01

During a Phase-I effort, studies were planned to evaluate deterministic (nonstochastic) effects of chronic exposure of nuclear workers at the Mayak atomic complex in the former Soviet Union to relatively high levels (> 0.25 Gy) of ionizing radiation. The Mayak complex has been used, since the late 1940's, to produce plutonium for nuclear weapons. Workers at Site A of the complex were involved in plutonium breeding using nuclear reactors, and some were exposed to relatively large doses of gamma rays plus relatively small neutron doses. The Weibull normalized-dose model, which has been set up to evaluate the risk of specific deterministic effects of combined, continuous exposure of humans to alpha, beta, and gamma radiations, is here adapted for chronic exposure to gamma rays and neutrons during repeated 6-h work shifts--as occurred for some nuclear workers at Site A. Using the adapted model, key conclusions were reached that will facilitate a Phase-II study of deterministic effects among Mayak workers. These conclusions include the following: (1) neutron doses may be more important for Mayak workers than for Japanese A-bomb victims in Hiroshima and can be accounted for using an adjusted dose (which accounts for neutron relative biological effectiveness); (2) to account for dose-rate effects, normalized dose X (a dimensionless fraction of an LD50 or ED50) can be evaluated in terms of an adjusted dose; (3) nonlinear dose-response curves for the risk of death via the hematopoietic mode can be converted to linear dose-response curves (for low levels of risk) using a newly proposed dimensionless dose, D = X(V), in units of Oklad (where D is pronounced "deh"), and V is the shape parameter in the Weibull model; (4) for X < or = Xo, where Xo is the threshold normalized dose, D = 0; (5) unlike absorbed dose, the dose D can be averaged over different Mayak workers in order to calculate the average risk of death via the hematopoietic mode for the population exposed at Site A; and (6) the expected cases of death via the hematopoietic syndrome mode for Mayak workers chronically exposed during work shifts at Site A to gamma rays and neutrons can be predicted using ln(2)B M[D]; where B (pronounced "beh") is the number of workers at risk (criticality accident victims excluded); and M[D] is the average (mean) value of D (averaged over the worker population at risk, for Site A, for the time period considered). These results can be used to facilitate a Phase II study of deterministic radiation effects among Mayak workers chronically exposed to gamma rays and neutrons.

Evaluation of surface and shallow depth dose reductions using a Superflab bolus during conventional and advanced external beam radiotherapy.

PubMed

Yoon, Jihyung; Xie, Yibo; Zhang, Rui

2018-03-01

The purpose of this study was to evaluate a methodology to reduce scatter and leakage radiations to patients' surface and shallow depths during conventional and advanced external beam radiotherapy. Superflab boluses of different thicknesses were placed on top of a stack of solid water phantoms, and the bolus effect on surface and shallow depth doses for both open and intensity-modulated radiotherapy (IMRT) beams was evaluated using thermoluminescent dosimeters and ion chamber measurements. Contralateral breast dose reduction caused by the bolus was evaluated by delivering clinical postmastectomy radiotherapy (PMRT) plans to an anthropomorphic phantom. For the solid water phantom measurements, surface dose reduction caused by the Superflab bolus was achieved only in out-of-field area and on the incident side of the beam, and the dose reduction increased with bolus thickness. The dose reduction caused by the bolus was more significant at closer distances from the beam. Most of the dose reductions occurred in the first 2-cm depth and stopped at 4-cm depth. For clinical PMRT treatment plans, surface dose reductions using a 1-cm Superflab bolus were up to 31% and 62% for volumetric-modulated arc therapy and 4-field IMRT, respectively, but there was no dose reduction for Tomotherapy. A Superflab bolus can be used to reduce surface and shallow depth doses during external beam radiotherapy when it is placed out of the beam and on the incident side of the beam. Although we only validated this dose reduction strategy for PMRT treatments, it is applicable to any external beam radiotherapy and can potentially reduce patients' risk of developing radiation-induced side effects. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Morphological changes induced by different doses of gamma irradiation in garlic sprouts

NASA Astrophysics Data System (ADS)

Pellegrini, C. N.; Croci, C. A.; Orioli, G. A.

2000-03-01

The objective of this work was to evaluate the effects of different doses of gamma rays applied in dormancy and post-dormancy on garlic bulbs in relation with some morphophysiological parameters. High (commercial) doses cause the complete inhibition of sprouting and mitosis (due to nuclear aberrations). Relatively low doses show no effects on bulbs but doses of 10 Gy applied in post-dormancy reduce sprouting and stop mitosis. This inhibition becomes noticeable from 150 days post-harvest onwards. Exogenous growth regulators can reverse these effects. Results may reinforce the good practice of radioinhibition processes in garlic.

EVALUATION OF EYE LENS DOSE TO WORKERS IN THE STEAM GENERATOR AT THE KOREAN OPTIMIZED POWER REACTOR 1000.

PubMed

Maeng, Sung Jun; Kim, Jinhwan; Cho, Gyuseong

2018-03-15

ICRP (2011) revised the dose limit to the eye lens to 20 mSv/y based on a recent epidemiological study of radiation-induced cataracts. Maintenance of steam generators at nuclear power plants is one of the highest radiation-associated tasks within a non-uniform radiation field. This study aims to evaluate eye lens doses in the steam generators of the Korean OPR1000 design. The source term was characterized based on the CRUD-specific activity, and both the eye lens dose and organ dose were simulated using MCNP6 combined with an ICRP voxel phantom and a mesh phantom, respectively. The eye lens dose was determined to be 5.39E-02-9.43E-02 Sv/h, with a negligible effect by beta particles. As the effective dose was found to be 0.81-1.21 times the lens equivalent dose depending on the phantom angles, the former can be used to estimate the lens dose in the SG of the OPR1000 for radiation monitoring purposes.

Antipsychotic treatment dosing profile in patients with schizophrenia evaluated with electronic monitoring (MEMS®).

PubMed

Acosta, Francisco J; Ramallo-Fariña, Yolanda; Bosch, Esperanza; Mayans, Teresa; Rodríguez, Carlos J; Caravaca, Ana

2013-05-01

Although the Medication Event Monitoring System (MEMS®) device offers accurate information on treatment dosing profile, such profile has never been studied in patients with schizophrenia. Enhancing our knowledge on this issue would help in developing intervention strategies to improve adherence to antipsychotic treatment in these patients. 74 outpatients with schizophrenia were monitored with the MEMS device for a 3-month period, for evaluation of antipsychotic treatment dosing profile, possible influence of medication schedule-related variables, adherence to treatment--considering dose intake within prescribed timeframes--and possible Hawthorne's effect of using the MEMS device. Dose-omission gaps occurred in 18.7% of monitoring days, most frequently during weekends, almost significantly. Almost one-third of prescribed doses were taken out of prescribed time. Neither the prescribed number of daily doses nor the indicated time of the day for dose intake (breakfast, dinner), were associated with correct antipsychotic dosing. Excess-dose was rare in general, and more frequent out of prescribed dose timeframe. No Hawthorne's effect was found for the MEMS device. Adherence reached only 35% according to a definition that included dose intake within prescribed timeframes. Antipsychotic treatment dosing was considerably irregular among patients with schizophrenia. Strategies to reduce dose-omission gaps and increase dosing within prescribed timeframes seem to be necessary. Gaining knowledge on precise oral antipsychotic dosing profiles or the influence of schedule-related variables may be useful to design strategies towards enhancing adherence. There appears to be no Hawthorne's effect associated with the use of MEMS devices in outpatients with schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

PubMed

Loveman, E; Cooper, K; Bryant, J; Colquitt, J L; Frampton, G K; Clegg, A

2012-01-01

The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. The paucity of good-quality evidence should be considered when interpreting this report. This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

Evaluation of effective dose for a patient under Ga-67 nuclear examination using TLD, water phantom and a simplified model

PubMed Central

Chu, Kuang Hua; Lin, Yu Ting; Hsu, Chia Chun; Chen, Chien Yi; Pan, Lung Kwang

2012-01-01

This study evaluated the effective dose of Ga-67 for a patient undergoing Ga-67 citrate nuclear examination by applying thermoluminescent dosimeter (TLD) technique and an indigenous water phantom. The Ga-67 radionuclide remaining in the body inevitably generated a measurable internal dose even though gamma camera scanning took only minutes to complete the clinical examination. For effective simulation of the cumulated effective dose for a patient undergoing examination, 150 TLDs were placed inside the water phantom for 6 days to monitor the gamma ray dose from the distributed Ga-67 citrate solution. The inserted TLDs represented internal organs, and the effective dose was calculated according to data in the ICRP-60 report. The water phantom was designed to model the body of a healthy human weighing 70 kg, and the water that was mixed with Ga-67 citrate solution was slowly replaced with fresh feed water to yield the required biological half life of the phantom. After continuously feeding in fresh water throughout the 6 days of TLD exposure, the TLDs were analyzed to determine the effective doses from the various biological half lives of the phantom. The derived effective dose of 185 MBq Ga-67 citrate solution for male/female (M/F) was 10.7/12.2, 10.7/12.0, 8.7/9.9 and 6.0/6.8 mSv, of biological half lives of 6.0, 4.5, 3.0 and 1.5 days, respectively. Although these experimental results correlated well with earlier empirical studies, they were lower than most calculated values. The cumulated uncertainty in the effective dose was 12.5–19.4%, which was acceptable in terms of both TLD counting statistic and reproducibility. PMID:22915780

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

Non-vascular interventional procedures: effective dose to patient and equivalent dose to abdominal organs by means of DICOM images and Monte Carlo simulation.

PubMed

Longo, Mariaconcetta; Marchioni, Chiara; Insero, Teresa; Donnarumma, Raffaella; D'Adamo, Alessandro; Lucatelli, Pierleone; Fanelli, Fabrizio; Salvatori, Filippo Maria; Cannavale, Alessandro; Di Castro, Elisabetta

2016-03-01

This study evaluates X-ray exposure in patient undergoing abdominal extra-vascular interventional procedures by means of Digital Imaging and COmmunications in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to assess the effective and equivalent doses, under the hypothesis of their correlation with the dose area product (DAP) measured during each examination. This allows to collect dosimetric information about each patient and to evaluate associated risks without resorting to in vivo dosimetry. The dose calculation was performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based Monte Carlo program for calculating patient doses in medical X-ray examinations), by using the real geometrical and dosimetric irradiation conditions, automatically extracted from DICOM headers. The DAP measurements were also validated by using thermoluminescent dosemeters on an anthropomorphic phantom. The expected linear correlation between effective doses and DAP was confirmed with an R(2) of 0.974. Moreover, in order to easily calculate patient doses, conversion coefficients that relate equivalent doses to measurable quantities, such as DAP, were obtained. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiation dose distributions due to sudden ejection of cobalt device.

PubMed

Abdelhady, Amr

2016-09-01

The evaluation of the radiation dose during accident in a nuclear reactor is of great concern from the viewpoint of safety. One of important accident must be analyzed and may be occurred in open pool type reactor is the rejection of cobalt device. The study is evaluating the dose rate levels resulting from upset withdrawal of co device especially the radiation dose received by the operator in the control room. Study of indirect radiation exposure to the environment due to skyshine effect is also taken into consideration in order to evaluate the radiation dose levels around the reactor during the ejection trip. Microshield, SHLDUTIL, and MCSky codes were used in this study to calculate the radiation dose profiles during cobalt device ejection trip inside and outside the reactor building. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

PubMed

McKeand, William

2017-09-01

Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation. Food did not seem to have any clinically relevant impact on pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of ~6% and was safe and well tolerated in the range of doses evaluated. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis.

PubMed

Venkatesh, Mohan Pammi; Rong, Liang

2008-09-01

Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of age. Lactoferrin, which is present in human milk, is a component of innate immunity and has broad-spectrum antimicrobial activity. The synergistic effects of lactoferrin with antibiotics against neonatal isolates have not been systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS and three strains (two neonatal) of Candida albicans were studied. MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method with serial twofold dilutions. Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90% inhibitory effect at several drug-dose ratios. It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions. In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant. Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents commonly used in neonatal practice and is a promising agent that needs to be evaluated in clinical studies.

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

Dose-response studies and 'no-effect-levels' of N-nitroso compounds: some general aspects.

PubMed

Preussmann, R

1980-01-01

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of 'no-adverse-effect-levels'. Arguments in favor of the postulated 'irreversibility' of carcinogenic effects are based on dose-response studies, single dose and multigeneration experiments as well as on the concept of somatic mutation as the first step in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes should never be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available.

Diagnostic accuracy of 256-row multidetector CT coronary angiography with prospective ECG-gating combined with fourth-generation iterative reconstruction algorithm in the assessment of coronary artery bypass: evaluation of dose reduction and image quality.

PubMed

Ippolito, Davide; Fior, Davide; Franzesi, Cammillo Talei; Riva, Luca; Casiraghi, Alessandra; Sironi, Sandro

2017-12-01

Effective radiation dose in coronary CT angiography (CTCA) for coronary artery bypass graft (CABG) evaluation is remarkably high because of long scan lengths. Prospective electrocardiographic gating with iterative reconstruction can reduce effective radiation dose. To evaluate the diagnostic performance of low-kV CT angiography protocol with prospective ecg-gating technique and iterative reconstruction (IR) algorithm in follow-up of CABG patients compared with standard retrospective protocol. Seventy-four non-obese patients with known coronary disease treated with artery bypass grafting were prospectively enrolled. All the patients underwent 256 MDCT (Brilliance iCT, Philips) CTCA using low-dose protocol (100 kV; 800 mAs; rotation time: 0.275 s) combined with prospective ECG-triggering acquisition and fourth-generation IR technique (iDose 4 ; Philips); all the lengths of the bypass graft were included in the evaluation. A control group of 42 similar patients was evaluated with a standard retrospective ECG-gated CTCA (100 kV; 800 mAs).On both CT examinations, ROIs were placed to calculate standard deviation of pixel values and intra-vessel density. Diagnostic quality was also evaluated using a 4-point quality scale. Despite the statistically significant reduction of radiation dose evaluated with DLP (study group mean DLP: 274 mGy cm; control group mean DLP: 1224 mGy cm; P value < 0.001). No statistical differences were found between PGA group and RGH group regarding intra-vessel density absolute values and SNR. Qualitative analysis, evaluated by two radiologists in "double blind", did not reveal any significant difference in diagnostic quality of the two groups. The development of high-speed MDCT scans combined with modern IR allows an accurate evaluation of CABG with prospective ECG-gating protocols in a single breath hold, obtaining a significant reduction in radiation dose.

Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumida, Iori, E-mail: sumida@radonc.med.osaka-u.ac.jp; Yamaguchi, Hajime; Kizaki, Hisao

2015-07-15

Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV,more » spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.« less

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

PubMed

Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T; Kuntz, Karen M

2014-11-04

Gout is the most common inflammatory arthritis in the United States. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. Markov model. Published literature and expert opinion. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. Lifetime. Health care payer. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. Long-term outcome data for patients with gout, including medication adherence, are limited. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. Agency for Healthcare Research and Quality.

Combining web-based tools for transparent evaluation of data for risk assessment: developmental effects of bisphenol A on the mammary gland as a case study.

PubMed

Molander, Linda; Hanberg, Annika; Rudén, Christina; Ågerstrand, Marlene; Beronius, Anna

2017-03-01

Different tools have been developed that facilitate systematic and transparent evaluation and handling of toxicity data in the risk assessment process. The present paper sets out to explore the combined use of two web-based tools for study evaluation and identification of reliable data relevant to health risk assessment. For this purpose, a case study was performed using in vivo toxicity studies investigating low-dose effects of bisphenol A on mammary gland development. The reliability of the mammary gland studies was evaluated using the Science in Risk Assessment and Policy (SciRAP) criteria for toxicity studies. The Health Assessment Workspace Collaborative (HAWC) was used for characterizing and visualizing the mammary gland data in terms of type of effects investigated and reported, and the distribution of these effects within the dose interval. It was then investigated whether there was any relationship between study reliability and the type of effects reported and/or their distribution in the dose interval. The combination of the SciRAP and HAWC tools allowed for transparent evaluation and visualization of the studies investigating developmental effects of BPA on the mammary gland. The use of these tools showed that there were no apparent differences in the type of effects and their distribution in the dose interval between the five studies assessed as most reliable and the whole data set. Combining the SciRAP and HAWC tools was found to be a useful approach for evaluating in vivo toxicity studies and identifying reliable and sensitive information relevant to regulatory risk assessment of chemicals. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Evaluation of β-blocker gel and effect of dosing volume for topical delivery.

PubMed

Zhang, Qian; Chantasart, Doungdaw; Li, S Kevin

2015-05-01

Although topical administration of β-blockers is desired because of the improved therapeutic efficacy and reduced systemic adverse effects compared with systemic administration in the treatment of infantile hemangioma, the permeation of β-blockers across skin under finite dose conditions has not been systematically studied and an effective topical β-blocker formulation for skin application is not available. The present study evaluated the permeation of β-blockers propranolol, betaxolol, and timolol across human epidermal membrane (HEM) from a topical gel in Franz diffusion cells in vitro under various dosing conditions. The effects of occlusion and dosing volume on percutaneous absorption of β-blockers from the gel were studied. The permeation data were compared with those of finite dose diffusion theory. The results showed that skin permeation of β-blockers generally could be enhanced two to three times by skin occlusion. The cumulative amounts of β-blockers permeated across HEM increased with increasing dosing volume. An adequate fit was obtained between the theoretical curve and experimental permeation data, indicating that the experimental results of the gel are consistent with finite dose diffusion theory. In conclusion, the findings suggest the feasibility of using topical gels of β-blockers for infantile hemangioma treatment and topical application with skin occlusion is preferred. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of an in vitro method for the evaluation of candidate repellents against Leptotrombidium (Acari: Trombiculidae) chiggers.

PubMed

Lerdthusnee, Kriangkrai; Khlaimanee, Nittaya; Monkanna, Taweesak; Mungviriya, Siriporn; Leepitakrat, Warisa; Debboun, Mustapha; Coleman, Russell E

2003-01-01

We developed a rapid and economical in vitro procedure with which to evaluate the efficacy of candidate repellents against chiggers. The procedure requires only 5 min and a small number of chiggers to obtain a valid estimate of the median effective dose. We used this procedure to evaluate the repellent activity of 11 compounds against the chigger, Leptotrombidium imphalum Vercammen-Grandjean and Langston. Median effective doses were determined for 10 of the 11 compounds. DM-165-2 (N,N-diethyl-3-flurobenzamide) was the only compound that was significantly more effective than deet.

Lack of Response in an Autistic Population to a Low Dose Clinical Trial of Pyridoxine Plus Magnesium.

ERIC Educational Resources Information Center

Tolbert, Lelland; And Others

1993-01-01

As some therapeutic benefits for autistic persons have been reported from combined high doses of pyridoxine and magnesium, this study evaluated long-term administration of low doses (to minimize adverse effects) to 15 subjects with autism. Findings indicated that, at this dosage level, pyridoxine and magnesium had no effect on the severity of…

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Burton, Page; Mechoulam, Raphael

2004-01-01

Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.

Correlation of radiation dose and heart rate in dual-source computed tomography coronary angiography.

PubMed

Laspas, Fotios; Tsantioti, Dimitra; Roussakis, Arkadios; Kritikos, Nikolaos; Efthimiadou, Roxani; Kehagias, Dimitrios; Andreou, John

2011-04-01

Computed tomography coronary angiography (CTCA) has been widely used since the introduction of 64-slice scanners and dual-source CT technology, but the relatively high radiation dose remains a major concern. To evaluate the relationship between radiation exposure and heart rate (HR), in dual-source CTCA. Data from 218 CTCA examinations, performed with a dual-source 64-slices scanner, were statistically evaluated. Effective radiation dose, expressed in mSv, was calculated as the product of the dose-length product (DLP) times a conversion coefficient for the chest (mSv = DLPx0.017). Heart rate range and mean heart rate, expressed in beats per minute (bpm) of each individual during CTCA, were also provided by the system. Statistical analysis of effective dose and heart rate data was performed by using Pearson correlation coefficient and two-sample t-test. Mean HR and effective dose were found to have a borderline positive relationship. Individuals with a mean HR >65 bpm observed to receive a statistically significant higher effective dose as compared to those with a mean HR ≤65 bpm. Moreover, a strong correlation between effective dose and variability of HR of more than 20 bpm was observed. Dual-source CT scanners are considered to have the capability to provide diagnostic examinations even with high HR and arrhythmias. However, it is desirable to keep the mean heart rate below 65 bpm and heart rate fluctuation less than 20 bpm in order to reduce the radiation exposure.

Effectiveness of a Third Dose of MMR Vaccine for Mumps Outbreak Control.

PubMed

Cardemil, Cristina V; Dahl, Rebecca M; James, Lisa; Wannemuehler, Kathleen; Gary, Howard E; Shah, Minesh; Marin, Mona; Riley, Jacob; Feikin, Daniel R; Patel, Manisha; Quinlisk, Patricia

2017-09-07

The effect of a third dose of the measles-mumps-rubella (MMR) vaccine in stemming a mumps outbreak is unknown. During an outbreak among vaccinated students at the University of Iowa, health officials implemented a widespread MMR vaccine campaign. We evaluated the effectiveness of a third dose for outbreak control and assessed for waning immunity. Of 20,496 university students who were enrolled during the 2015-2016 academic year, mumps was diagnosed in 259 students. We used Fisher's exact test to compare unadjusted attack rates according to dose status and years since receipt of the second MMR vaccine dose. We used multivariable time-dependent Cox regression models to evaluate vaccine effectiveness, according to dose status (three vs. two doses and two vs. no doses) after adjustment for the number of years since the second dose. Before the outbreak, 98.1% of the students had received at least two doses of MMR vaccine. During the outbreak, 4783 received a third dose. The attack rate was lower among the students who had received three doses than among those who had received two doses (6.7 vs. 14.5 cases per 1000 population, P<0.001). Students had more than nine times the risk of mumps if they had received the second MMR dose 13 years or more before the outbreak. At 28 days after vaccination, receipt of the third vaccine dose was associated with a 78.1% lower risk of mumps than receipt of a second dose (adjusted hazard ratio, 0.22; 95% confidence interval, 0.12 to 0.39). The vaccine effectiveness of two doses versus no doses was lower among students with more distant receipt of the second vaccine dose. Students who had received a third dose of MMR vaccine had a lower risk of mumps than did those who had received two doses, after adjustment for the number of years since the second dose. Students who had received a second dose of MMR vaccine 13 years or more before the outbreak had an increased risk of mumps. These findings suggest that the campaign to administer a third dose of MMR vaccine improved mumps outbreak control and that waning immunity probably contributed to propagation of the outbreak. (Funded by the Centers for Disease Control and Prevention.).

An improved MCNP version of the NORMAN voxel phantom for dosimetry studies.

PubMed

Ferrari, P; Gualdrini, G

2005-09-21

In recent years voxel phantoms have been developed on the basis of tomographic data of real individuals allowing new sets of conversion coefficients to be calculated for effective dose. Progress in radiation studies brought ICRP to revise its recommendations and a new report, already circulated in draft form, is expected to change the actual effective dose evaluation method. In the present paper the voxel phantom NORMAN developed at HPA, formerly NRPB, was employed with MCNP Monte Carlo code. A modified version of the phantom, NORMAN-05, was developed to take into account the new set of tissues and weighting factors proposed in the cited ICRP draft. Air kerma to organ equivalent dose and effective dose conversion coefficients for antero-posterior and postero-anterior parallel photon beam irradiations, from 20 keV to 10 MeV, have been calculated and compared with data obtained in other laboratories using different numerical phantoms. Obtained results are in good agreement with published data with some differences for the effective dose calculated employing the proposed new tissue weighting factors set in comparison with previous evaluations based on the ICRP 60 report.

Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath (registered) technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fransson, Per; Bergstroem, Per; Loefroth, Per-Olov

2006-10-01

Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique. Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath (registered) technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (nmore » = 74), and 78 Gy (n = 53). Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy. Conclusion: Dose-escalated EBRT with the BeamCath (registered) technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.« less

Radiation dose evaluation of dental cone beam computed tomography using an anthropomorphic adult head phantom

NASA Astrophysics Data System (ADS)

Wu, Jay; Shih, Cheng-Ting; Ho, Chang-hung; Liu, Yan-Lin; Chang, Yuan-Jen; Min Chao, Max; Hsu, Jui-Ting

2014-11-01

Dental cone beam computed tomography (CBCT) provides high-resolution tomographic images and has been gradually used in clinical practice. Thus, it is important to examine the amount of radiation dose resulting from dental CBCT examinations. In this study, we developed an in-house anthropomorphic adult head phantom to evaluate the level of effective dose. The anthropomorphic phantom was made of acrylic and filled with plaster to replace the bony tissue. The contour of the head was extracted from a set of adult computed tomography (CT) images. Different combinations of the scanning parameters of CBCT were applied. Thermoluminescent dosimeters (TLDs) were used to measure the absorbed doses at 19 locations in the head and neck regions. The effective doses measured using the proposed phantom at 65, 75, and 85 kVp in the D-mode were 72.23, 100.31, and 134.29 μSv, respectively. In the I-mode, the effective doses were 108.24, 190.99, and 246.48 μSv, respectively. The maximum percent error between the doses measured by the proposed phantom and the Rando phantom was l4.90%. Therefore, the proposed anthropomorphic adult head phantom is applicable for assessing the radiation dose resulting from clinical dental CBCT.

Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

PubMed

Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

2016-09-01

Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Effective DQE (eDQE) and dose to optimize radiographic technical parameters: a survey of pediatric chest X-ray examinations in Korea.

PubMed

Park, Hye-Suk; Kim, Ye-Seul; Park, Ok-Seob; Kim, Sang-Tae; Jeon, Chang-Woo; Kim, Hee-Joung

2014-04-01

The purpose of this study was to investigate the effect of various technical parameters for dose optimization in pediatric chest radiological examinations by evaluating effective dose and effective detective quantum efficiency (eDQE). For tube voltages ranging from 40 to 90 kV in 10 kV increments at the focus-to-detector distance (FDD) of 100, 110, 120, 150, 180 cm, the eDQE was evaluated at same effective dose. The eDQE was considerably higher without the use of the grid on equivalent effective dose. This indicates that the reduction of scatter radiation did not compensate for the loss of absorbed effective photons in the grid. The eDQE increased with increasing FDD because of the greater effective modulation transfer function (eMTF) with lower focal spot blurring. However, most of the major hospitals in Korea employed a short FDD of 100 cm with the grid. The entrance surface air kerma values for the hospitals of this survey exceeded the Korean reference level of 100 μGy. The different reference levels might be appropriate for the same examination conducted on children of different ages. Also, it is necessary to refine the technical parameters to perform pediatric chest examinations.

Processing speed can monitor stimulant-medication effects in adults with attention deficit disorder with hyperactivity.

PubMed

Nielsen, Niels Peter; Wiig, Elisabeth H; Bäck, Svante; Gustafsson, Jan

2017-05-01

Treatment responses to methylphenidate by adults with ADHD are generally monitored against DSM-IV/DSM-V symptomatology, rating scales or interviews during reviews. To evaluate the use of single- and dual-dimension processing-speed and efficiency measures to monitor the effects of pharmacological treatment with methylphenidate after a short period off medication. A Quick Test of Cognitive Speed (AQT) monitored the effects of immediate-release methylphenidate in 40 previously diagnosed and medicated adults with ADHD. Processing speed was evaluated with prior prescription medication, without medication after a 2-day period off ADHD medication, and with low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride (Medikinet IR). Thirty-three participants responded to the experimental treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant main effects for single dimension colour and form and dual-dimension colour-form naming. Post-hoc analysis indicated statistical differences between the no- and high-dose medication conditions for colour and form, measures of perceptual speed. For colour-form naming, a measure of cognitive speed, there was a significant difference between no- and low-dose medication and between no- and high-dose medications, but not between low- and high-dose medications. Results indicated that the AQT tests effectively monitored incremental effects of the methylphenidate dose on processing speed after a 2-day period off medication. Thus, perceptual (colour and form) and cognitive speed (two-dimensional colour-form naming) and processing efficiency (lowered shift costs) increased measurably with high-dose medication. These preliminary findings warrant validation with added measures of associated behavioural and cognitive changes.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

PubMed Central

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai

2017-01-01

Abstract Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction. PMID:29281130

First-principles X-ray absorption dose calculation for time-dependent mass and optical density.

PubMed

Berejnov, Viatcheslav; Rubinstein, Boris; Melo, Lis G A; Hitchcock, Adam P

2018-05-01

A dose integral of time-dependent X-ray absorption under conditions of variable photon energy and changing sample mass is derived from first principles starting with the Beer-Lambert (BL) absorption model. For a given photon energy the BL dose integral D(e, t) reduces to the product of an effective time integral T(t) and a dose rate R(e). Two approximations of the time-dependent optical density, i.e. exponential A(t) = c + aexp(-bt) for first-order kinetics and hyperbolic A(t) = c + a/(b + t) for second-order kinetics, were considered for BL dose evaluation. For both models three methods of evaluating the effective time integral are considered: analytical integration, approximation by a function, and calculation of the asymptotic behaviour at large times. Data for poly(methyl methacrylate) and perfluorosulfonic acid polymers measured by scanning transmission soft X-ray microscopy were used to test the BL dose calculation. It was found that a previous method to calculate time-dependent dose underestimates the dose in mass loss situations, depending on the applied exposure time. All these methods here show that the BL dose is proportional to the exposure time D(e, t) ≃ K(e)t.

Measurement of Individual Doses of Radiation by Personal Dosimeter Is Important for the Return of Residents from Evacuation Order Areas after Nuclear Disaster

PubMed Central

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual’s house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster. PMID:25806523

Measurement of individual doses of radiation by personal dosimeter is important for the return of residents from evacuation order areas after nuclear disaster.

PubMed

Orita, Makiko; Hayashida, Naomi; Taira, Yasuyuki; Fukushima, Yoshiko; Ide, Juichi; Endo, Yuuko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

2015-01-01

To confirm the availability of individual dose evaluation for the return of residents after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FNPP), we evaluated individual doses of radiation as measured by personal dosimeters in residents who temporarily stayed in Evacuation Order Areas in Kawauchi village, which is partially located within a 20 km radius of the FNPP. We also compared individual doses with the external radiation doses estimated from the ambient dose rates and with doses estimated from the concentrations of radionuclides in the soil around each individual's house. Individual doses were significantly correlated with the ambient doses in front of the entrances to the houses (r = 0.90, p<0.01), in the backyards (r = 0.41, p<0.01) and in the nearby fields (r = 0.80, p<0.01). The maximum cumulative ambient doses in the backyards and fields around the houses were 6.38 and 9.27 mSv/y, respectively. The maximum cumulative individual dose was 3.28 mSv/y, and the median and minimum doses were 1.35 and 0.71 mSv/y. The estimated external effective doses from concentrations of artificial radionuclides in soil samples ranged from 0.03 to 23.42 mSv/y. The individual doses were moderately correlated with external effective doses in the backyards (r = 0.38, p<0.01) and in the fields (r = 0.36, p<0.01); however, the individual doses were not significantly correlated with the external effective doses in front of the entrances (r = 0.01, p = 0.92). Our study confirmed that individual doses are low levels even in the evacuation order area in Kawauchi village, and external effective dose levels are certainly decreasing due to the decay of artificial radionuclides and the decontamination of contaminated soil. Long-term follow-up of individual doses as well as internal-exposure doses, environmental monitoring and reconstruction of infrastructure are needed so that residents may return to their hometowns after a nuclear disaster.

Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

PubMed

Natale, Stephanie; Bradley, John; Nguyen, William Huy; Tran, Tri; Ny, Pamela; La, Kirsten; Vivian, Eva; Le, Jennifer

2017-03-01

Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients. © 2017 Pharmacotherapy Publications, Inc.

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

PubMed Central

Wang, Wei-Hong; Huang, Jia-Qing; Zheng, Ge-Fan; Xia, Harry Hua-Xiang; Wong, Wai-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu

2005-01-01

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis. PMID:15996033

Blonanserin – A Novel Antianxiety and Antidepressant Drug? An Experimental Study

PubMed Central

Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

2016-01-01

Introduction Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. Aim The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. Materials and Methods By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. Results This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. Conclusion The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies. PMID:27790460

Blonanserin - A Novel Antianxiety and Antidepressant Drug? An Experimental Study.

PubMed

Limaye, Ramchandra Prabhakar; Patil, Aditi Nitin

2016-09-01

Many psychiatric disorders show signs and symptoms of anxiety and depression. A drug with both, effects and lesser adverse effects is always desired. Blonanserin is a novel drug with postulated effect on anxiety and depression. The study was aimed to evaluate the effect of Blonanserin on anxiety and depression in animal models. By using elevated plus maze test and forced swimming test, the antianxiety and antidepressant effects were evaluated. Animal ethics protocols were followed strictly. Total 50 rats (10 rats per group) were used for each test. As a control drug diazepam and imipramine were used in elevated plus maze and forced swimming test respectively. Blonanserin was tested for 3 doses 0.075, 0.2 and 0.8mg. These doses were selected from previous references as well as by extrapolating human doses. This study showed an antianxiety effect of Blonanserin comparable to diazepam, which was statistically significant. Optimal effect was observed with 0.075mg, followed by 0.2 and 0.8mg. It also showed an antidepressant effect which was statistically significant. Optimal effect was observed at 0.2mg dose. The results showed that at a dose range of 0.075 and 0.2mg Blonanserin has potential to exert an adjuvant antianxiety and antidepressant activity in animal models. In order to extrapolate this in patient, longer clinical studies with comparable doses should be planned. The present study underlines potential of Blonanserin as a novel drug for such studies.

Evaluation and implementation of triple‐channel radiochromic film dosimetry in brachytherapy

PubMed Central

Bradley, David; Nisbet, Andrew

2014-01-01

The measurement of dose distributions in clinical brachytherapy, for the purpose of quality control, commissioning or dosimetric audit, is challenging and requires development. Radiochromic film dosimetry with a commercial flatbed scanner may be suitable, but careful methodologies are required to control various sources of uncertainty. Triple‐channel dosimetry has recently been utilized in external beam radiotherapy to improve the accuracy of film dosimetry, but its use in brachytherapy, with characteristic high maximum doses, steep dose gradients, and small scales, has been less well researched. We investigate the use of advanced film dosimetry techniques for brachytherapy dosimetry, evaluating uncertainties and assessing the mitigation afforded by triple‐channel dosimetry. We present results on postirradiation film darkening, lateral scanner effect, film surface perturbation, film active layer thickness, film curling, and examples of the measurement of clinical brachytherapy dose distributions. The lateral scanner effect in brachytherapy film dosimetry can be very significant, up to 23% dose increase at 14 Gy, at ± 9 cm lateral from the scanner axis for simple single‐channel dosimetry. Triple‐channel dosimetry mitigates the effect, but still limits the useable width of a typical scanner to less than 8 cm at high dose levels to give dose uncertainty to within 1%. Triple‐channel dosimetry separates dose and dose‐independent signal components, and effectively removes disturbances caused by film thickness variation and surface perturbations in the examples considered in this work. The use of reference dose films scanned simultaneously with brachytherapy test films is recommended to account for scanner variations from calibration conditions. Postirradiation darkening, which is a continual logarithmic function with time, must be taken into account between the reference and test films. Finally, films must be flat when scanned to avoid the Callier‐like effects and to provide reliable dosimetric results. We have demonstrated that radiochromic film dosimetry with GAFCHROMIC EBT3 film and a commercial flatbed scanner is a viable method for brachytherapy dose distribution measurement, and uncertainties may be reduced with triple‐channel dosimetry and specific film scan and evaluation methodologies. PACS numbers: 87.55.Qr, 87.56.bg, 87.55.km PMID:25207417

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No. 200900420)« less

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Ultralow-dose computed tomography imaging for surgery of midfacial and orbital fractures using ASIR and MBIR.

PubMed

Widmann, G; Dalla Torre, D; Hoermann, R; Schullian, P; Gassner, E M; Bale, R; Puelacher, W

2015-04-01

The influence of dose reductions on diagnostic quality using a series of high-resolution ultralow-dose computed tomography (CT) scans for computer-assisted planning and surgery including the most recent iterative reconstruction algorithms was evaluated and compared with the fracture detectability of a standard cranial emergency protocol. A human cadaver head including the mandible was artificially prepared with midfacial and orbital fractures and scanned using a 64-multislice CT scanner. The CT dose index volume (CTDIvol) and effective doses were calculated using application software. Noise was evaluated as the standard deviation in Hounsfield units within an identical region of interest in the posterior fossa. Diagnostic quality was assessed by consensus reading of a craniomaxillofacial surgeon and radiologist. Compared with the emergency protocol at CTDIvol 35.3 mGy and effective dose 3.6 mSv, low-dose protocols down to CTDIvol 1.0 mGy and 0.1 mSv (97% dose reduction) may be sufficient for the diagnosis of dislocated craniofacial fractures. Non-dislocated fractures may be detected at CTDIvol 2.6 mGy and 0.3 mSv (93% dose reduction). Adaptive statistical iterative reconstruction (ASIR) 50 and 100 reduced average noise by 30% and 56%, and model-based iterative reconstruction (MBIR) by 93%. However, the detection rate of fractures could not be improved due to smoothing effects. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

PubMed Central

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-01-01

Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

PubMed

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-12-01

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

Occupational dose in interventional radiology procedures.

PubMed

Chida, Koichi; Kaga, Yuji; Haga, Yoshihiro; Kataoka, Nozomi; Kumasaka, Eriko; Meguro, Taiichiro; Zuguchi, Masayuki

2013-01-01

Interventional radiology tends to involve long procedures (i.e., long fluoroscopic times). Therefore, radiation protection for interventional radiology staff is an important issue. This study describes the occupational radiation dose for interventional radiology staff, especially nurses, to clarify the present annual dose level for interventional radiology nurses. We compared the annual occupational dose (effective dose and dose equivalent) among interventional radiology staff in a hospital where 6606 catheterization procedures are performed annually. The annual occupational doses of 18 physicians, seven nurses, and eight radiologic technologists were recorded using two monitoring badges, one worn over and one under their lead aprons. The annual mean ± SD effective dose (range) to the physicians, nurses, and radiologic technologists using two badges was 3.00 ± 1.50 (0.84-6.17), 1.34 ± 0.55 (0.70-2.20), and 0.60 ± 0.48 (0.02-1.43) mSv/y, respectively. Similarly, the annual mean ± SD dose equivalent range was 19.84 ± 12.45 (7.0-48.5), 4.73 ± 0.72 (3.9-6.2), and 1.30 ± 1.00 (0.2-2.7) mSv/y, respectively. The mean ± SD effective dose for the physicians was 1.02 ± 0.74 and 3.00 ± 1.50 mSv/y for the one- and two-badge methods, respectively (p < 0.001). Similarly, the mean ± SD effective dose for the nurses (p = 0.186) and radiologic technologists (p = 0.726) tended to be lower using the one-badge method. The annual occupational dose for interventional radiology staff was in the order physicians > nurses > radiologic technologists. The occupational dose determined using one badge under the apron was far lower than the dose obtained with two badges in both physicians and nonphysicians. To evaluate the occupational dose correctly, we recommend use of two monitoring badges to evaluate interventional radiology nurses as well as physicians.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters.

PubMed

Cortés-Gutiérrez, Elva I; Cerda-Flores, Ricardo M; González-Ramírez, Diego; Zúñiga-Charles, Miguel A; Lazcano-Martínez, Sigifredo; Sampayo-Reyes, Adriana; Leal-Garza, Carlos H

2004-05-01

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).

Pre-medication and renal pre-conditioning: a role for alprazolam, atropine, morphine and promethazine.

PubMed

Pazoki-Toroudi, Hamid Reza; Ajami, Marjan; Habibey, Rouhollah

2010-04-01

Four pre-medication drugs are used to relieve pain, allay anxiety, reduce secretion and enhance hypnosis, were evaluated for their effects on ischemia reperfusion (I/R) injury which is one of the major complications of vascular and transplantation surgery. Right kidney was removed from female rats (210-250 g) 3 weeks before surgical procedure. Different doses of morphine (0.5, 2 and 5 mg/kg), promethazine (1, 2 and 5 mg/kg), atropine (0.1, 0.3 and 0.5 mg/kg) and alprazolam (0.08, 0.32 and 0.64 mg/kg) were administered subcutaneously 30 min before left renal artery occlusion and 6 h reperfusion. Left kidneys were processed for histological evaluations. Creatinine and BUN were measured in serum samples. Morphine, promethazine, atropine and alprazolam at all evaluated doses significantly decreased serum creatinine and BUN levels and histopathological scores. The effects of promethazine (1 mg/kg) and all doses of alprazolam were more potent than other pre-medication drugs and doses. This study suggested a protective effect of these pre-medication drugs on I/R injury. Although obvious studies are required, these findings may lead to effective therapies against I/R injury.

High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea.

PubMed

Zhu, Yirui; Reinach, Peter S; Zhu, Hanlei; Tan, Qiufan; Zheng, Qinxiang; Qu, Jia; Chen, Wei

2017-01-01

Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

Does Iterative Reconstruction Lower CT Radiation Dose: Evaluation of 15,000 Examinations

PubMed Central

Noël, Peter B.; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A.; Rummeny, Ernst J.; Dobritz, Martin

2013-01-01

Purpose Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Method and Materials Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. Results IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). Conclusion The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving. PMID:24303035

Does iterative reconstruction lower CT radiation dose: evaluation of 15,000 examinations.

PubMed

Noël, Peter B; Renger, Bernhard; Fiebich, Martin; Münzel, Daniela; Fingerle, Alexander A; Rummeny, Ernst J; Dobritz, Martin

2013-01-01

Evaluation of 15,000 computed tomography (CT) examinations to investigate if iterative reconstruction (IR) reduces sustainably radiation exposure. Information from 15,000 CT examinations was collected, including all aspects of the exams such as scan parameter, patient information, and reconstruction instructions. The examinations were acquired between January 2010 and December 2012, while after 15 months a first generation IR algorithm was installed. To collect the necessary information from PACS, RIS, MPPS and structured reports a Dose Monitoring System was developed. To harvest all possible information an optical character recognition system was integrated, for example to collect information from the screenshot CT-dose report. The tool transfers all data to a database for further processing such as the calculation of effective dose and organ doses. To evaluate if IR provides a sustainable dose reduction, the effective dose values were statistically analyzed with respect to protocol type, diagnostic indication, and patient population. IR has the potential to reduce radiation dose significantly. Before clinical introduction of IR the average effective dose was 10.1±7.8mSv and with IR 8.9±7.1mSv (p*=0.01). Especially in CTA, with the possibility to use kV reduction protocols, such as in aortic CTAs (before IR: average14.2±7.8mSv; median11.4mSv /with IR:average9.9±7.4mSv; median7.4mSv), or pulmonary CTAs (before IR: average9.7±6.2mSV; median7.7mSv /with IR: average6.4±4.7mSv; median4.8mSv) the dose reduction effect is significant(p*=0.01). On the contrary for unenhanced low-dose scans of the cranial (for example sinuses) the reduction is not significant (before IR:average6.6±5.8mSv; median3.9mSv/with IR:average6.0±3.1mSV; median3.2mSv). The dose aspect remains a priority in CT research. Iterative reconstruction algorithms reduce sustainably and significantly radiation dose in the clinical routine. Our results illustrate that not only in studies with a limited number of patients but also in the clinical routine, IRs provide long-term dose saving.

Patient radiation dose from computed tomography angiography and digital subtraction angiography of the brain

NASA Astrophysics Data System (ADS)

Netwong, Y.; Krisanachinda, A.

2016-03-01

The 64-row multidetector computed tomography angiography (64-MDCTA) provides vascular image quality of the brain similar to digital subtraction angiography (DSA), but the effective dose of CTA is lower than DSA studied in phantom. The purpose of this study is to evaluate the effective dose from 64-MDCTA and DSA. Effective dose (according to ICRP 103) from 64-MDCTA and DSA flat panel detector for cerebral vessels examination of the brain using standard protocols as recommended by the manufacturer was calculated for 30 cases of MDCTA (15 male and 15 female).The mean patient age was 49.5 (23-89) yrs. 30 cases of DSA (14 male and 16 female), the mean patient age was 46.8 (21-81) yrs. For CTA, the mean effective dose was 3.7 (2.82- 5.19) mSv. For DSA, the mean effective dose was 5.78 (3.3-10.06) mSv. The effective dose of CTA depends on the scanning protocol and scan length. Low tube current can reduce patient dose whereas the number of exposures and number of series in 3D rotational angiography (3D RA) resulted in increasing effective dose in DSA patients.

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

PubMed

Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

2014-10-01

Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

[Comparison of Organ Dose Calculation Using Monte Carlo Simulation and In-phantom Dosimetry in CT Examination].

PubMed

Iriuchijima, Akiko; Fukushima, Yasuhiro; Ogura, Akio

Direct measurement of each patient organ dose from computed tomography (CT) is not possible. Most methods to estimate patient organ dose is using Monte Carlo simulation with dedicated software. However, the method and the relative differences between organ dose simulation and measurement is unclear. The purpose of this study was to compare organ doses evaluated by Monte Carlo simulation with doses evaluated by in-phantom dosimetry. The simulation software Radimetrics (Bayer) was used for the calculation of organ dose. Measurement was performed with radio-photoluminescence glass dosimeter (RPLD) set at various organ positions within RANDO phantom. To evaluate difference of CT scanner, two different CT scanners were used in this study. Angular dependence of RPLD and measurement of effective energy were performed for each scanner. The comparison of simulation and measurement was evaluated by relative differences. In the results, angular dependence of RPLD at two scanners was 31.6±0.45 mGy for SOMATOM Definition Flash and 29.2±0.18 mGy for LightSpeed VCT. The organ dose was 42.2 mGy (range, 29.9-52.7 mGy) by measurements and 37.7 mGy (range, 27.9-48.1 mGy) by simulations. The relative differences of organ dose between measurement and simulation were 13%, excluding of breast's 42%. We found that organ dose by simulation was lower than by measurement. In conclusion, the results of relative differences will be useful for evaluating organ doses for individual patients by simulation software Radimetrics.

Optimization of exposure parameters for pediatric chest x-ray imaging

NASA Astrophysics Data System (ADS)

Park, Hye-Suk; Kim, Ye-Seul; Kim, Hee-Joung

2012-03-01

The pediatric patients are more susceptible to the effects of ionizing radiation than adults. Pediatric patients are smaller, more radiosensitive than adult patients and many cannot stand unassisted. Their characteristics affect the method of imaging projection and how dose is optimized. The purpose of this study was to investigate the effect of various technical parameters for the dose optimization in pediatric chest radiological examinations by evaluating effective dose and effective detective quantum efficiency (eDQE) including the scatter radiation from the object, the blur caused by the focal spot, geometric magnification and detector characteristics. For the tube voltages ranging from 40 to 90 kV in 10 kV increments at the focus-to-detector distance of 100, 110, 120, 150, 180 cm, the eDQE was evaluated at same effective dose. The results showed that the eDQE was largest at 60 kVp without and with an anti-scatter grid. Especially, the eDQE was considerably higher without the use of an anti-scatter grid on equivalent effective dose. This indicates that the reducing the scatter radiation did not compensate for the loss of absorbed effective photons in the grid. When the grid is not used the eDQE increased with increasing focus-to-detector distance because of the greater effective modulation transfer function (eMTF) with the lower focal spot blurring. In conclusion, for pediatric patients, the amount of scattered radiation is less, and the amount of grid attenuation increased unnecessary radiation dose.

Radiation exposure in interventional radiology

NASA Astrophysics Data System (ADS)

Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

2007-09-01

The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

Critical evaluation of taeniacidal antibiotic S15-1 (SQ 21, 704) for removal of natural tapeworm infections in dogs and cats.

PubMed

Szanto, J; Lillis, W G; Brown, W E; Sutphin, C F; Maplesden, D C

1979-05-01

The new taeniacidal antibiotic S15-1 (SQ 21,704) was evaluated against naturally occuring infections of Taenia pisiformis in 53 dogs, Dipylidium caninum in 35 dogs, T taeniaformis in 18 cats, and D caninum in 33 cats. It all instances, the compound was administered in gelatine capsules in a single oral dose. The doses tested were between and 200 mg/kg of body weight in dogs and between 15 and 45 mg/kg in cats. In dogs, doses of 25 mg/kg and greater were 100% effective against T pisiformis, whereas a dose of 50 mg/kg was necessary to clear D caninum. In cats, a single oral dose of 22.5 mg/kg was 100% efficacious against T taeniaeformis, and a single dose of 45 mg/kg (the largest dose tested) clearly seven of eight cats of D caninum. The efficacy was limited to tapeworms only; there was no efficacy against nematodes. The antibiotic was well tolerated by both species with no drug-related vomiting or other side-effects observed.

Assessing doses to interventional radiologists using a personal dosimeter worn over a protective apron.

PubMed

Stranden, E; Widmark, A; Sekse, T

2008-05-01

Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.

Quantifying Children's Aggregate (Dietary and Residential) Exposure and Dose to Permethin: Application and Evaluation of EPA's Probabilistic SHED-Multimedia Model

EPA Science Inventory

Reliable, evaluated human exposure and dose models are important for understanding the health risks from chemicals. A case study focusing on permethrin was conducted because of this insecticide’s widespread use and potential health effects. SHEDS-Multimedia was applied to estimat...

Process evaluation of the Enabling Mothers toPrevent Pediatric Obesity Through Web-Based Learning and Reciprocal Determinism (EMPOWER) randomized control trial.

PubMed

Knowlden, Adam P; Sharma, Manoj

2014-09-01

Family-and-home-based interventions are an important vehicle for preventing childhood obesity. Systematic process evaluations have not been routinely conducted in assessment of these interventions. The purpose of this study was to plan and conduct a process evaluation of the Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Learning and Reciprocal Determinism (EMPOWER) randomized control trial. The trial was composed of two web-based, mother-centered interventions for prevention of obesity in children between 4 and 6 years of age. Process evaluation used the components of program fidelity, dose delivered, dose received, context, reach, and recruitment. Categorical process evaluation data (program fidelity, dose delivered, dose exposure, and context) were assessed using Program Implementation Index (PII) values. Continuous process evaluation variables (dose satisfaction and recruitment) were assessed using ANOVA tests to evaluate mean differences between groups (experimental and control) and sessions (sessions 1 through 5). Process evaluation results found that both groups (experimental and control) were equivalent, and interventions were administered as planned. Analysis of web-based intervention process objectives requires tailoring of process evaluation models for online delivery. Dissemination of process evaluation results can advance best practices for implementing effective online health promotion programs. © 2014 Society for Public Health Education.

The effect of various doses of pheromone on mating disruption in gypsy moth population

Treesearch

Ksenia Tcheslavskaia; Alexei A. Sharov; Kevin W. Thorpe; Carlyle C. Brewster

2003-01-01

An experiment was conducted in June-August 2001 in the Cumberland and Appomattox- Buckingham State Forests, Virginia to evaluate the effects of various doses of synthetic pheromone (racemic disparlure) on mating disruption of the gypsy moth, Lymantria dispar (L.).

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect?

PubMed

Kushner, Pamela R; Peura, David A

2011-05-01

Proton pump inhibitors (PPIs) are widely used in clinical practice. However, concerns have been expressed about their long-term use, particularly with regard to bone health, Clostridium difficile infections, and drug interactions with platelet aggregation inhibitors. There has been limited guidance for clinicians concerning appropriate dose selection of PPIs for the initial treatment of heartburn. This review explored whether published clinical trials provide evidence of a ceiling above which higher PPI doses do not provide additional clinical benefit over the lowest approved dose. All articles of randomized, controlled clinical trials in nonerosive gastroesophageal reflux disease (GERD) in which the effects of two or more doses of the same PPI on symptomatic relief of heartburn were quantified as a study endpoint were identified and analyzed through PubMed searches up to the end of September 2010. The majority of trials evaluated provided no evidence that higher PPI doses were superior to the lowest approved dose for the initial treatment of heartburn. There were no clinically relevant findings with respect to dose dependence and safety outcomes in these studies. Efficacy outcomes from the trials suggest there may be a dose ceiling effect and highlight the need for further research on the use of the lowest effective PPI doses as an appropriate strategy in the initial treatment of uncomplicated heartburn. Observational studies and some meta-analyses have suggested that long-term PPI pharmacotherapy might be associated with safety concerns, which necessitate the periodic evaluation of therapeutic benefit in terms of symptom resolution and regimen tolerability. However, evidence to date suggests that use of the lowest effective dose for the indication is not associated with significant adverse events, particularly in the short term. Clinical practice suggests that patients requiring long-term treatment should be maintained on the lowest dose necessary to control symptoms, and monitored for potentially confounding factors that may lead to safety concerns.

Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

PubMed

Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

2015-07-01

Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siebers, Jeffrey V.; Keall, Paul J.; Wu Qiuwen

2005-10-01

Purpose: The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. Methods and Materials: Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errorsmore » of {sigma} = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with {sigma} = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for {sigma} = {sigma} = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D{sub 98}), clinical target volume (CTV) D{sub 90}, nodes D{sub 90}, cord D{sub 2}, and parotid D{sub 50} and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. Results: Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error {sigma} exceeded 3 mm. Simulated systematic setup errors with {sigma} = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a {sigma} = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with {sigma} = {sigma} = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the {sigma} = {sigma} = 3.0 mm simulations to 5.4% of the plans simulated. Conclusions: Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.« less

Increased dose near the skin due to electromagnetic surface beacon transponder.

PubMed

Ahn, Kang-Hyun; Manger, Ryan; Halpern, Howard J; Aydogan, Bulent

2015-05-08

The purpose of this study was to evaluate the increased dose near the skin from an electromagnetic surface beacon transponder, which is used for localization and tracking organ motion. The bolus effect due to the copper coil surface beacon was evaluated with radiographic film measurements and Monte Carlo simulations. Various beam incidence angles were evaluated for both 6 MV and 18 MV experimentally. We performed simulations using a general-purpose Monte Carlo code MCNPX (Monte Carlo N-Particle) to supplement the experimental data. We modeled the surface beacon geometry using the actual mass of the glass vial and copper coil placed in its L-shaped polyethylene terephthalate tubing casing. Film dosimetry measured factors of 2.2 and 3.0 enhancement in the surface dose for normally incident 6 MV and 18 MV beams, respectively. Although surface dose further increased with incidence angle, the relative contribution from the bolus effect was reduced at the oblique incidence. The enhancement factors were 1.5 and 1.8 for 6 MV and 18 MV, respectively, at an incidence angle of 60°. Monte Carlo simulation confirmed the experimental results and indicated that the epidermal skin dose can reach approximately 50% of the dose at dmax at normal incidence. The overall effect could be acceptable considering the skin dose enhancement is confined to a small area (~ 1 cm2), and can be further reduced by using an opposite beam technique. Further clinical studies are justified in order to study the dosimetric benefit versus possible cosmetic effects of the surface beacon. One such clinical situation would be intact breast radiation therapy, especially large-breasted women.

Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

PubMed

Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

2016-03-01

Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation.

PubMed

Roch-Lefèvre, Sandrine; Grégoire, Eric; Martin-Bodiot, Cécile; Flegal, Matthew; Fréneau, Amélie; Blimkie, Melinda; Bannister, Laura; Wyatt, Heather; Barquinero, Joan-Francesc; Roy, Laurence; Benadjaoud, Mohamed; Priest, Nick; Jourdain, Jean-René; Klokov, Dmitry

2018-06-08

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

Field evaluations of the VD max approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

NASA Astrophysics Data System (ADS)

Kowalski, John B.; Herring, Craig; Baryschpolec, Lisa; Reger, John; Patel, Jay; Feeney, Mary; Tallentire, Alan

2002-08-01

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD max for quarterly dose audits; Facility B compared VD max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment. The field evaluations of the VD max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD max experiments were consistent with the outcomes observed with Method 1. The VD max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

PubMed

Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

Effective doses to family members of patients treated with radioiodine-131

NASA Astrophysics Data System (ADS)

Zdraveska Kocovska, M.; Vaskova, O.; Majstorov, V.; Kuzmanovska, S.; Pop Gjorceva, D.; Spasic Jokic, V.

2011-09-01

The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine-131, and also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses, sixty family members of sixty patients, treated with radioiodine-131, and thermoluminiscent dosimeters (Model TLD 100) were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79). The estimated effective doses to family members of hyperthyroid patients were higher than the effective doses to family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, H. Y.; Tung, C. J.; Yu, C. C.

2007-04-15

The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinationsmore » was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.« less

Air contamination measurements for the evaluation of internal dose to workers in nuclear medicine departments

NASA Astrophysics Data System (ADS)

De Massimi, B.; Bianchini, D.; Sarnelli, A.; D'Errico, V.; Marcocci, F.; Mezzenga, E.; Mostacci, D.

2017-11-01

Radionuclides handled in nuclear medicine departments are often characterized by high volatility and short half-life. It is generally difficult to monitor directly the intake of these short-lived radionuclides in hospital staff: this makes measuring air contamination of utmost interest. The aim of the present work is to provide a method for the evaluation of internal doses to workers in nuclear medicine, by means of an air activity sampling detector, to ensure that the limits prescribed by the relevant legislation are respected. A continuous air sampling system measures isotope concentration with a Nal(TI) detector. Energy efficiency of the system was assessed with GEANT4 and with known activities of 18F. Air is sampled in a number of areas of the nuclear medicine department of the IRST-IRCCS hospital (Meldola- Italy). To evaluate committed doses to hospital staff involved (doctors, technicians, nurses) different exposure situations (rooms, times, radionuclides etc) were considered. After estimating the intake, the committed effective dose has been evaluated, for the different radionuclides, using the dose coefficients mandated by the Italian legislation. Error propagation for the estimated intake and personal dose has been evaluated, starting from measurement statistics.

Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach.

PubMed

Sarrabay, A; Hilmi, C; Tinwell, H; Schorsch, F; Pallardy, M; Bars, R; Rouquié, D

2015-12-15

The dose-response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose-response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LH increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (<0.1mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1mg/kg/day, as well as an increase in testosterone blood level at 10mg/kg/day. Each key event dose-response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose-response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

PubMed

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

Radon survey and soil gamma doses in primary schools of Batman, Turkey.

PubMed

Damla, Nevzat; Aldemir, Kamuran

2014-06-01

A survey was conducted to evaluate levels of indoor radon and gamma doses in 42 primary schools located in Batman, southeastern Anatolia, Turkey. Indoor radon measurements were carried out using CR-39 solid-state nuclear track detector-based radon dosimeters. The overall mean annual (222)Rn activity in the surveyed area was found to be 49 Bq m(-3) (equivalent to an annual effective dose of 0.25 mSv). However, in one of the districts (Besiri) the maximum radon value turned out to be 307 Bq m(-3). The estimated annual effective doses are less than the recommended action level (3-10 mSv). It is found that the radon concentration decreases with increasing floor number. The concentrations of natural and artificial radioisotopes were determined using gamma-ray spectroscopy for soil samples collected in close vicinity of the studied schools. The mean gamma activity concentrations in the soil samples were 31, 25, 329 and 12 Bq kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, respectively. The radiological parameters such as the absorbed dose rate in air and the annual effective dose equivalent were calculated. These radiological parameters were evaluated and compared with the internationally recommended values.

Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.

PubMed

Bartošová, O; Bonnet, C; Ulmanová, O; Šíma, M; Perlík, F; Růžička, E; Slanař, O

2018-04-01

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2  = 0.78) and the total daily L-DOPA dose (R 2  = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

Use of radiation protraction to escalate biologically effective dose to the treatment target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuperman, V. Y.; Spradlin, G. S.; Department of Mathematics, Embry-Riddle University, Daytona Beach, Florida 32114

2011-12-15

Purpose: The aim of this study is to evaluate how simultaneously increasing fraction time and dose per fraction affect biologically effective dose for the target (BED{sub tar}) while biologically effective dose for the normal tissue (BED{sub nt}) is fixed. Methods: In this investigation, BED{sub tar} and BED{sub nt} were studied by assuming mono-exponential repair of sublethal damage with tissue dependent repair half-time. Results: Our results demonstrate that under certain conditions simultaneously increasing fraction time and dose per fraction result in increased BED{sub tar} while BED{sub nt} is fixed. The dependence of biologically effective dose on fraction time is influenced bymore » the dose rate. In this investigation we analytically determined time-varying dose rate R-tilde which minimizes BED. Changes in BED with fraction time were compared for constant dose rate and for R-tilde. Conclusions: A number of recent experimental and theoretical studies have demonstrated that slow delivery of radiation (known as radiation protraction) leads to reduced therapeutic effect because of increased repair of sublethal damage. In contrast, our analysis shows that under certain conditions simultaneously increasing fraction time and dose per fraction are radiobiologically advantageous.« less

Estimation of patient radiation dose from whole body 18F- FDG PET/CT examination in cancer imaging: a preliminary study

NASA Astrophysics Data System (ADS)

Mahmud, M. H.; Nordin, A. J.; Saad, F. F. Ahmad; Fattah Azman, A. Z.

2014-11-01

This study aims to estimate the radiation effective dose resulting from whole body fluorine-18 flourodeoxyglucose Positron Emission Tomography (18F-FDG PET) scanning as compared to conservative Computed Tomography (CT) techniques in evaluating oncology patients. We reviewed 19 oncology patients who underwent 18F-FDG PET/CT at our centre for cancer staging. Internal and external doses were estimated using radioactivity of injected FDG and volume CT Dose Index (CTDIvol), respectively with employment of the published and modified dose coefficients. The median differences of dose among the conservative CT and PET protocols were determined using Kruskal Wallis test with p < 0.05 considered as significant. The median (interquartile range, IQR) effective doses of non-contrasted CT, contrasted CT and PET scanning protocols were 7.50 (9.35) mSv, 9.76 (3.67) mSv and 6.30 (1.20) mSv, respectively, resulting in the total dose of 21.46 (8.58) mSv. Statistically significant difference was observed in the median effective dose between the three protocols (p < 0.01). The effective doses of whole body 18F-FDG PET technique may be effective the lowest amongst the conventional CT imaging techniques.

Adaptive radiation therapy of prostate cancer

NASA Astrophysics Data System (ADS)

Wen, Ning

ART is a close-loop feedback algorithm which evaluates the organ deformation and motion right before the treatment and takes into account dose delivery variation daily to compensate for the difference between planned and delivered dose. It also has potential to allow further dose escalation and margin reduction to improve the clinical outcome. This retrospective study evaluated ART for prostate cancer treatment and radiobiological consequences. An IRB approved protocol has been used to evaluate actual dose delivery of patients with prostate cancer undergoing treatment with daily CBCT. The dose from CBCT was measured in phantom using TLD and ion chamber techniques in the pelvic scan setting. There were two major findings from the measurements of CBCT dose: (1) the lateral dose distribution was not symmetrical, with Lt Lat being ˜40% higher than Rt Lat and (2) AP skin dose varies with patient size, ranging 3.2--6.1 cGy for patient's AP separation of 20--33 cm (the larger the separation, the less the skin dose) but lateral skin doses depend little on separations. Dose was recalculated on each CBCT set under the same treatment plan. DIR was performed between SIM-CT and evaluated for each CT sets. Dose was reconstructed and accumulated to reflect the actual dose delivered to the patient. Then the adaptive plans were compared to the original plan to evaluate tumor control and normal tissue complication using radiobiological model. Different PTV margins were also studied to access margin reduction techniques. If the actual dose delivered to the PTV deviated significantly from the prescription dose for the given fractions or the OAR received higher dose than expected, the treatment plan would be re-optimized based on the previously delivered dose. The optimal schedule was compared based on the balance of PTV dose coverage and inhomogeneity, OAR dose constraints and labor involved. DIR was validated using fiducial marker position, visual comparison and UE. The mean and standard deviation of markers after rigid registration in L-R direction was 0 and 1 mm. But the mean was 2--4 mm in the A-P and S-I direction and standard deviation was about 2 mm. After DIR, the mean in all three directions became 0 and standard deviation was within sub millimeter. UE images were generated for each CT set and carefully reviewed in the prostate region. DIR provided accurate transformation matrix to be used for dose reconstruction. The delivered dose was evaluated with radiobiological models. TCP for the CTV was calculated to evaluate tumor control in different margin settings. TCP calculated from the reconstructed dose agreed within 5% of the value in the plan for all patients with three different margins. EUD and NTCP were calculated to evaluate reaction of rectum to radiation. Similar biological evaluation was performed for bladder. EUD of actual dose was 3%--9% higher than that of planned dose of patient 1--3, 11%--20% higher of patient 4--5. Smaller margins could not reduce late GU toxicity effectively since bladder complication was directly related to Dmax which was at the same magnitude in the bladder no matter which margin was applied. Re-optimization was performed at the 10th, 20th , 30th, and 40th fraction to evaluate the effectiveness to limit OAR dose while maintaining the target coverage. Reconstructed dose was added to dose from remaining fractions after optimization to show the total dose patient would receive. It showed that if the plan was re-optimized at 10th or 20th fraction, total dose to rectum and bladder were very similar to planned dose with minor deviations. If the plan was re-optimized at the 30th fraction, since there was a large deviation between reconstructed dose and planned dose to OAR, optimization could not limit the OAR dose to the original plan with only 12 fractions left. If the re-optimization was done at the 40th fraction, it was impossible to compensate in the last 2 fractions. Large deviations of total dose to bladder and rectum still existed while dose inhomogeneity to PTV was significantly increased due to hard constraints set in the optimization to reduce OAR dose. In summary, ART did not show improvements in TCP if the patient was setup with CBCT. However, EUD of rectum and bladder was increased significantly due to tissue deformation which varied daily. With the power of ART, margins added to the CTV could be further reduced to preserve critical organs surrounding the target. (Abstract shortened by UMI.)

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

PubMed Central

Brouwer, A; Longnecker, M P; Birnbaum, L S; Cogliano, J; Kostyniak, P; Moore, J; Schantz, S; Winneke, G

1999-01-01

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included. PMID:10421775

Using Population Dose to Evaluate Community-level Health Initiatives.

PubMed

Harner, Lisa T; Kuo, Elena S; Cheadle, Allen; Rauzon, Suzanne; Schwartz, Pamela M; Parnell, Barbara; Kelly, Cheryl; Solomon, Loel

2018-05-01

Successful community-level health initiatives require implementing an effective portfolio of strategies and understanding their impact on population health. These factors are complicated by the heterogeneity of overlapping multicomponent strategies and availability of population-level data that align with the initiatives. To address these complexities, the population dose methodology was developed for planning and evaluating multicomponent community initiatives. Building on the population dose methodology previously developed, this paper operationalizes dose estimates of one initiative targeting youth physical activity as part of the Kaiser Permanente Community Health Initiative, a multicomponent community-level obesity prevention initiative. The technical details needed to operationalize the population dose method are explained, and the use of population dose as an interim proxy for population-level survey data is introduced. The alignment of the estimated impact from strategy-level data analysis using the dose methodology and the data from the population-level survey suggest that dose is useful for conducting real-time evaluation of multiple heterogeneous strategies, and as a viable proxy for existing population-level surveys when robust strategy-level evaluation data are collected. This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation and Mitigation of Secondary Dose Delivered to Electronic Systems in Proton Therapy.

PubMed

Wroe, Andrew J

2016-02-01

To evaluate the scattered and secondary radiation fields present in and around a passive proton treatment nozzle. In addition, based on these initial tests and system reliability analysis, to develop, install, and evaluate a radiation shielding structure to protect sensitive electronics against single-event effects (SEE) and improve system reliability. Landauer Luxel+ dosimeters were used to evaluate the radiation field around one of the gantry-mounted passive proton delivery nozzles at Loma Linda University Medical Center's James M Slater, MD Proton Treatment and Research Center. These detectors use optically stimulated luminescence technology in conjunction with CR-39 to measure doses from X-ray, gamma, proton, beta, fast neutron, and thermal neutron radiation. The dosimeters were stationed at various positions around the gantry pit and attached to racks on the gantry itself to evaluate the dose to electronics. Wax shielding was also employed on some detectors to evaluate the usefulness of this material as a dose moderator. To create the scattered and secondary radiation field in the gantry enclosure, a polystyrene phantom was placed at isocenter and irradiated with 250 MeV protons to a dose of 1.3 kGy over 16 hours. Using the collected data as a baseline, a composite shielding structure was created and installed to shield electronics associated with the precision patient positioner. The effectiveness of this shielding structure was evaluated with Landauer Luxel+ dosimeters and the results correlated against system uptime. The measured dose equivalent ranged from 1 to 60 mSv, with proton/photon, thermal neutron, fast neutron, and overall dose equivalent evaluated. The position of the detector/electronics relative to both isocenter and also neutron-producing devices, such as the collimators and first and second scatterers, definitely had a bearing on the dose received. The addition of 1-inch-thick wax shielding decreased the fast neutron component by almost 50%, yet this yielded a corresponding average increase in thermal neutron dose of 150% as there was no Boron-10 component to capture thermal neutrons. Using these data as a reference, a shielding structure was designed and installed to minimize radiation to electronics associated with the patient positioner. The installed shielding reduced the total dose experienced by these electronics by a factor of 5 while additionally reducing the fast and thermal neutron doses by a factor of 7 and 14, respectively. The reduction in radiation dose corresponded with a reduction of SEE-related downtime of this equipment from 16.5 hours to 2.5 hours over a 6-month reporting period. The data obtained in this study provided a baseline for radiation exposures experienced by gantry- and pit-mounted electronic systems. It also demonstrated and evaluated a shielding structure design that can be retrofitted to existing electronic system installations. It is expected that this study will benefit future upgrades and facility designs by identifying mechanisms that may minimize radiation dose to installed electronics, thus improving facility uptime. © The Author(s) 2015.

On the sensitivity of TG-119 and IROC credentialing to TPS commissioning errors.

PubMed

McVicker, Drew; Yin, Fang-Fang; Adamson, Justus D

2016-01-08

We investigate the sensitivity of IMRT commissioning using the TG-119 C-shape phantom and credentialing with the IROC head and neck phantom to treatment planning system commissioning errors. We introduced errors into the various aspects of the commissioning process for a 6X photon energy modeled using the analytical anisotropic algorithm within a commercial treatment planning system. Errors were implemented into the various components of the dose calculation algorithm including primary photons, secondary photons, electron contamination, and MLC parameters. For each error we evaluated the probability that it could be committed unknowingly during the dose algorithm commissioning stage, and the probability of it being identified during the verification stage. The clinical impact of each commissioning error was evaluated using representative IMRT plans including low and intermediate risk prostate, head and neck, mesothelioma, and scalp; the sensitivity of the TG-119 and IROC phantoms was evaluated by comparing dosimetric changes to the dose planes where film measurements occur and change in point doses where dosimeter measurements occur. No commissioning errors were found to have both a low probability of detection and high clinical severity. When errors do occur, the IROC credentialing and TG 119 commissioning criteria are generally effective at detecting them; however, for the IROC phantom, OAR point-dose measurements are the most sensitive despite being currently excluded from IROC analysis. Point-dose measurements with an absolute dose constraint were the most effective at detecting errors, while film analysis using a gamma comparison and the IROC film distance to agreement criteria were less effective at detecting the specific commissioning errors implemented here.

HLW Flexible jumper materials compatibility evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skidmore, T. E.

H-Tank Farm Engineering tasked SRNL/Materials Science & Technology (MS&T) to evaluate the compatibility of Goodyear Viper® chemical transfer hose with HLW solutions. The hose is proposed as a flexible Safety Class jumper for up to six months service. SRNL/MS&T performed various tests to evaluate the effects of radiation, high pH chemistry and elevated temperature on the hose, particularly the inner liner. Test results suggest an upper dose limit of 50 Mrad for the hose. Room temperature burst pressure values at 50 Mrad are estimated at 600- 800 psi, providing a safety factor of 4.0-5.3X over the anticipated operating pressure ofmore » 150 psi and a safety factor of 3.0-4.0X over the working pressure of the hose (200 psi), independent of temperature effects. Radiation effects are minimal at doses less than 10 Mrad. Doses greater than 50 Mrad may be allowed, depending on operating conditions and required safety factors, but cannot be recommended at this time. At 250 Mrad, burst pressure values are reduced to the hose working pressure. At 300 Mrad, burst pressures are below 150 psi. At a bounding continuous dose rate of 57,870 rad/hr, the 50 Mrad dose limit is reached within 1.2 months. Actual dose rates may be lower, particularly during non-transfer periods. Refined dose calculations are therefore recommended to justify longer service. This report details the tests performed and interpretation of the results. Recommendations for shelf-life/storage, component quality verification, and post-service examination are provided.« less

Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.

PubMed

Thomas, C; Patschan, O; Ketelsen, D; Tsiflikas, I; Reimann, A; Brodoefel, H; Buchgeister, M; Nagele, U; Stenzl, A; Claussen, C; Kopp, A; Heuschmid, M; Schlemmer, H-P

2009-06-01

The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo.

EVALUATION OF EYE LENS DOSES OF INTERVENTIONAL CARDIOLOGISTS.

PubMed

Yokoyama, Sumi; Suzuki, Shoichi; Toyama, Hiroshi; Arakawa, Shinji; Inoue, Satoshi; Kinomura, Yutaka; Kobayashi, Ikuo

2017-04-01

The effective dose of medical staff members, especially interventional radiologists and cardiologists, is classified as a relatively high level. We measured the dose for interventional cardiologists by using optically stimulated luminescence dosimeters (OSLDs). However, this quantity is not the same as Hp (3). In experiments, the dose at the eye-lens position of a phantom were measured using OSLDs and thermoluminescence dosimeters (TLDs). A conversion factor from dose measured by using TLDs to OSLDs was estimated from these results. In addition, the eye doses of interventional cardiologists in clinical situations were measured, and the effect of eyewear on the eye-lens dose was discussed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Opioid Challenge Evaluation of Blockade by Extended-Release Naltrexone in Opioid-Abusing Adults: Dose-Effects and Time-Course

PubMed Central

Bigelow, George E.; Preston, Kenzie L.; Schmittner, John; Dong, Qunming; Gastfriend, David R.

2013-01-01

Background Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. Methods Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-hr intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) Visual Analog Scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. Results Blockade of the VAS “any drug effect” response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150 and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. Conclusions These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID:22079773

Evaluation of automatic exposure control system chamber for the dose optimization when examining pelvic in digital radiography.

PubMed

Kim, Sung-Chul; Lee, Hae-Kag; Lee, Yang-Sub; Cho, Jae-Hwan

2015-01-01

We found a way to optimize the image quality and reduce the exposure dose of patients through the proper activity combination of the automatic exposure control system chamber for the dose optimization when examining the pelvic anteroposterior side using the phantom of the human body standard model. We set 7 combinations of the chamber of automatic exposure control system. The effective dose was yielded by measuring five times for each according to the activity combination of the chamber for the dose measurement. Five radiologists with more than five years of experience evaluated the image through picture archiving and communication system using double blind test while classifying the 6 anatomical sites into 3-point level (improper, proper, perfect). When only one central chamber was activated, the effective dose was found to be the highest level, 0.287 mSv; and lowest when only the top left chamber was used, 0.165 mSv. After the subjective evaluation by five panel members on the pelvic image was completed, there was no statistically meaningful difference between the 7 chamber combinations, and all had good image quality. When testing the pelvic anteroposterior side with digital radiography, we were able to reduce the exposure dose of patients using the combination of the top right side of or the top two of the chamber.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

PubMed

Chen, Grace; Nomikos, George G; Affinito, John; Zhao, Zhen

2016-09-01

Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

PubMed

Hirose, Tatsuya; Shinoda, Yasutaka; Kuroda, Ayaka; Yoshida, Aya; Mitsuoka, Machiko; Mori, Kouki; Kawachi, Yuki; Moriya, Akihiro; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

2018-01-01

Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases ( P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first ( P = 0.0133) and second ( P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Evaluation of forest decontamination using radiometric measurements.

PubMed

Cresswell, Alan J; Kato, Hiroaki; Onda, Yuichi; Nanba, Kenji

2016-11-01

An experiment has been conducted to evaluate the additional dose reduction by clear felling contaminated forestry in Fukushima Prefecture, Japan, and using the timber to cover the areas with wood chips. A portable gamma spectrometry system, comprising a backpack containing a 3 × 3″ NaI(Tl) detector with digital spectrometer and GPS receiver, has been used to map dose rate and radionuclide activity concentrations before, after and at stages during this experiment. The data show the effect of the different stages of the experiment on dose rate at different locations around the site. The spectrometric data have allowed the assessment of the contributions of natural and anthropogenic radionuclides to the dose rate at different parts of the site before and after the experiment. This has clearly demonstrated the value of radiometric methods in evaluating remediation, and the effect of other environmental processes. The value of spectrometric methods which directly measure radionuclide concentrations has also been shown, especially through the identification of the contribution of natural and anthropogenic activity to the measured dose rate. The experiment has shown that clearing trees and applying wood chips can reduce dose rates by 10-15% beyond that achieved by just clearing the forest litter and natural redistribution of radiocaesium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Tatsuya; Widder, Joachim; Dijk, Lisanne V. van

2016-11-01

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2.more » The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.« less

Assessment of the unattached fraction of indoor radon progeny and its contribution to dose: a pilot study in China.

PubMed

Guo, Qiuju; Zhang, Lei; Guo, Lu

2012-12-01

The unattached fraction of radon progeny (f(p)) is one of the most important factors for accurate evaluation of the effective dose from a unit of radon exposure, and it may vary greatly in different environments. For precise evaluation of the indoor radon exposure dose and the influence of unattached radon progeny, a pilot survey of f(p) in different environments was carried out in China with a portable and integrating monitor. The dose conversion factors for radon progeny are calculated with LUDEP(®) code, and the dose contributions from the unattached and the attached radon progenies were simultaneously evaluated based on the results of field measurements. The results show that even though the concentrations of radon progeny vary significantly among different indoor environments, the variations of f(p) seem relatively small (9.3-16.9%). The dose contribution from unattached radon progeny is generally larger (30.2-46.2%) in an indoor environment.

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

NASA Technical Reports Server (NTRS)

Ferl, J. E.; Long, E. R., Jr.

1981-01-01

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

Toxicological evaluation by in vitro and in vivo assays of an aqueous extract prepared from Echinodorus macrophyllus leaves.

PubMed

da Costa Lopes, L; Albano, F; Augusto Travassos Laranja, G; Marques Alves, L; Fernando Martins e Silva, L; Poubel de Souza, G; de Magalhães Araujo, I; Firmino Nogueira-Neto, J; Felzenszwalb, I; Kovary, K

2000-08-16

Toxicity of an aqueous extract prepared from Echinodorus macrophyllus dried leaves, a plant used in folk medicine to treat inflammation and kidney malfunctions, was estimated by different bioassays. Mutagenicity of the aqueous extract was evaluated in the Salmonella/microsome assay (TA97a, TA98, TA100 and TA102 strains), with or without metabolic activation. No mutagenic activity (lyophilized extract tested up to 50 mg/plate) could be detected to any of the tester strain. Furthermore, no cytotoxic effect has been observed when a crude extract of E. macrophyllus (up to 7.5 mg/ml) was tested on the exponential growth of hepatoma and normal kidney epithelial cells in culture. Toxicity of E. macrophyllus was also evaluated in male Swiss mice after 6 weeks of continuous ingestion of the aqueous extract in drinking water. Average daily ingested doses were 3, 23 and 297 mg/kg for a lyophilized extract, and 2200 mg/kg for a crude extract, with dose two being equivalent to the daily dose recommended to humans. At the end of the treatment, all animals revealed a deficit in final body weight ranging from 5 to 47%. Biochemical analysis of the plasma revealed some minor alterations indicating subclinical hepatic toxicity. Genotoxic effect on liver, kidney and blood cells has been also evaluated by the comet assay, being negative to liver and blood cells. However, DNA analyses of the kidney cells detected some genotoxic activity for the highest dose tested of E. macrophyllus extract, either lyophilized or crude. On the other hand, exposure dose of 23 mg/kg, equivalent to the daily dose recommended to humans, did not revealed any genotoxic effect and hence this herb seems to be safe to human organism.

Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.

PubMed

Nirogi, Ramakrishna; Mudigonda, Koteshwara; Bhyrapuneni, Gopinadh; Muddana, Nageswara Rao; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Palacharla, Raghava Choudary

2018-05-01

SUVN-502, a selective 5-HT6 receptor antagonist, was found to be active in preclinical models of cognitive deterioration suggesting a potential role in the treatment of dementia related to Alzheimer's disease. The objective of this study was to characterize the safety, tolerability and pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects following single and multiple oral doses. Single doses (5, 15, 50, 100 and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100 mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose) was evaluated using an open-label, two-period, randomized, fed and fasted in a crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored using validated analytical methods. SUVN-502 is safe and well tolerated up to the highest tested single dose of 200 mg in healthy young adults and multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more than dose-proportional over the evaluated dose range. Food and gender did not have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total (AUC 0-∞ , and AUC 0-last ) and peak exposures (C max ) were 2.9- and 2.2-fold higher, respectively, in elderly subjects compared to young subjects. Steady-state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of SUVN-502. SUVN-502 exhibited an acceptable safety, tolerability and pharmacokinetic profile in healthy young adults and elderly subjects. Based on the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to Phase 2 evaluation in patients with moderate AD.

Dose and time dependent ototoxicity of aspartame in rats.

PubMed

Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

2017-04-01

Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Effect of combined doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping.

PubMed

Rock, Erin M; Limebeer, Cheryl L; Parker, Linda A

2015-12-01

Δ(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 μg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 μg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 μg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning.

Radiation Therapy and Hearing Loss

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhandare, Niranjan; Jackson, Andrew; Eisbruch, Avraham

2010-03-01

A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associatedmore » ototoxicity as well as a detailed approach for scoring toxicity is presented.« less

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

ERIC Educational Resources Information Center

Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

1997-01-01

Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

Abuse liability assessment of eslicarbazepine acetate in healthy male and female recreational sedative users: A Phase I randomized controlled trial.

PubMed

Levy-Cooperman, Naama; Schoedel, Kerri A; Chakraborty, Bijan; Blum, David; Cheng, Hailong

2016-08-01

Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug for the treatment of partial-onset seizures. Adverse events such as dizziness and somnolence reported in clinical studies suggest that ESL has detectable central nervous system (CNS) effects in addition to its antiepileptic effects. This Phase I study evaluated the abuse liability of ESL compared with that of alprazolam (ALP) and placebo (PBO) in recreational CNS depressant users. In this single-dose, randomized, double-blind, PBO- and active-controlled crossover study, healthy recreational CNS depressant users who could discern between ALP 2mg and PBO received single oral doses of each of the following treatments with a washout interval of ≥7days between each treatment: ESL (800mg, 1600mg, 2000mg, and 2400mg); ALP (1.5mg and 3.0mg); and PBO. Subjective measures, including visual analog scales (VASs) e.g., Drug-Liking (primary endpoint), and Addiction Research Center Inventory (ARCI) Morphine-Benzedrine Group (MBG), Pentobarbital Chlorpromazine Alcohol Group (PCAG), and Lysergic Acid Diethylamide Group scales were evaluated at multiple time points up to 24h postdose. Cognitive effects were evaluated using the Choice Reaction Time (CRT), Divided Attention (DAT) and Hopkins Verbal Learning Task-Revised tests. Peak scores for Drug-Liking VAS (maximum effect [Emax]) were significantly higher for both ALP doses than for PBO (p<0.0001), thereby confirming study validity. Drug-Liking VAS Emax was significantly lower for all ESL doses than both ALP doses (p<0.0001). Drug-Liking VAS Emax for ESL 800mg was similar to that for PBO (least squares [LS] mean difference: 3.6; p=0.19). At the three higher ESL doses (1600mg and the supratherapeutic doses of 2000mg and 2400mg), Drug-Liking VAS Emax was significantly higher than for PBO, although the differences were minimal (LS mean difference: 9.3-13.3 out of 100). For most secondary subjective endpoints (i.e., Good Effects VAS and High VAS, ARCI-MBG, Take Drug Again VAS, Overall Drug-Liking VAS, and ARCI-PCAG; p<0.05), the effect of ESL (all doses) was significantly less than that of ALP (both doses). On most secondary measures, the dose-response relationship was relatively flat or showed saturation at higher ESL doses. Although significant differences were observed for ESL compared with those for PBO for some specific CRT and DAT endpoints (i.e., reaction time, manual tracking, hit latency), ALP demonstrated significant and dose-dependent impairment on the majority of cognitive endpoints when compared with PBO and ESL. Mean plasma concentrations of the active metabolite of ESL, eslicarbazepine, increased with increasing ESL dose. Pharmacokinetic parameters estimated for eslicarbazepine were generally comparable with results from previous studies in healthy volunteers. This study demonstrated that single doses of ESL may have less abuse liability than ALP in recreational sedative users. Although ESL had detectable subjective effects and showed some drug-'liking' at higher doses, the magnitude of these effects was small. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

On the dosimetric effect and reduction of inverse consistency and transitivity errors in deformable image registration for dose accumulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bender, Edward T.; Hardcastle, Nicholas; Tome, Wolfgang A.

2012-01-15

Purpose: Deformable image registration (DIR) is necessary for accurate dose accumulation between multiple radiotherapy image sets. DIR algorithms can suffer from inverse and transitivity inconsistencies. When using deformation vector fields (DVFs) that exhibit inverse-inconsistency and are nontransitive, dose accumulation on a given image set via different image pathways will lead to different accumulated doses. The purpose of this study was to investigate the dosimetric effect of and propose a postprocessing solution to reduce inverse consistency and transitivity errors. Methods: Four MVCT images and four phases of a lung 4DCT, each with an associated calculated dose, were selected for analysis. DVFsmore » between all four images in each data set were created using the Fast Symmetric Demons algorithm. Dose was accumulated on the fourth image in each set using DIR via two different image pathways. The two accumulated doses on the fourth image were compared. The inverse consistency and transitivity errors in the DVFs were then reduced. The dose accumulation was repeated using the processed DVFs, the results of which were compared with the accumulated dose from the original DVFs. To evaluate the influence of the postprocessing technique on DVF accuracy, the original and processed DVF accuracy was evaluated on the lung 4DCT data on which anatomical landmarks had been identified by an expert. Results: Dose accumulation to the same image via different image pathways resulted in two different accumulated dose results. After the inverse consistency errors were reduced, the difference between the accumulated doses diminished. The difference was further reduced after reducing the transitivity errors. The postprocessing technique had minimal effect on the accuracy of the DVF for the lung 4DCT images. Conclusions: This study shows that inverse consistency and transitivity errors in DIR have a significant dosimetric effect in dose accumulation; Depending on the image pathway taken to accumulate the dose, different results may be obtained. A postprocessing technique that reduces inverse consistency and transitivity error is presented, which allows for consistent dose accumulation regardless of the image pathway followed.« less

SPECT-CT in routine clinical practice: increase in patient radiation dose compared with SPECT alone.

PubMed

Sharma, Punit; Sharma, Shekhar; Ballal, Sanjana; Bal, Chandrasekhar; Malhotra, Arun; Kumar, Rakesh

2012-09-01

To assess the patient radiation dose during routine clinical single-photon emission computed tomography-computed tomography (SPECT-CT) and measure the increase as compared with SPECT alone. Data pertaining to 357 consecutive patients who had undergone radioisotope imaging along with SPECT-CT of a selected volume were retrospectively evaluated. Dose of the injected radiopharmaceutical (MBq) was noted, and the effective dose (mSv) was calculated as per International Commission on Radiological Protection (ICRP) guidelines. The volume-weighted computed tomography dose index (CTDIvol) and dose length product of the CT were also assessed using standard phantoms. The effective dose (mSv) due to CT was calculated as the product of dose length product and a conversion factor depending on the region of investigation, using ICRP guidelines. The dose due to CT was compared among different investigations. The increase in effective dose was calculated as CT dose expressed as a percentage of radiopharmaceutical dose. The per-patient CT effective dose for different studies varied between 0.06 and 11.9 mSv. The mean CT effective dose was lowest for 99mTc-ethylene cysteine dimer brain SPECT-CT (0.9 ± 0.7) and highest for 99mTc-methylene diphosphonate bone SPECT-CT (4.2 ± 2.8). The increase in radiation dose (SPECT-CT vs. SPECT) varied widely (2.3-666.4% for 99mTc-tracers and 0.02-96.2% for 131I-tracers). However, the effective dose of CT in SPECT-CT was less than the values reported for conventional CT examinations of the same regions. Addition of CT to nuclear medicine imaging in the form of SPECT-CT increases the radiation dose to the patient, with the effective dose due to CT exceeding the effective dose of RP in many instances. Hence, appropriate utilization and optimization of the protocols of SPECT-CT is needed to maximize benefit to patients.

Proton dose distribution measurements using a MOSFET detector with a simple dose‐weighted correction method for LET effects

PubMed Central

Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-01-01

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth‐dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high‐bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L‐shaped bolus. The dose reproducibility, angular dependence and depth‐dose response were evaluated using a 190 MeV proton beam. Depth‐output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose‐weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L‐shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors. PACS number: 87.56.‐v

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

PubMed

Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; tonic delivery of low EE, a dose that corresponds to the most popular doses used in the clinic today, did not impact cognition on any measure. Both medium and high injection doses of EE reduced the number of ChAt-immunoreactive cells in the basal forebrain, and cell population estimates in the vertical/diagonal bands negatively correlated with working memory errors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of ionizing radiation on charge-coupled imagers

NASA Technical Reports Server (NTRS)

Killiany, J. M.; Baker, W. D.; Saks, N. S.; Barbe, D. F.

1975-01-01

The effects of ionizing radiation on three different charge coupled imagers have been investigated. Device performance was evaluated as a function of total gamma ray dose. The principal failure mechanisms have been identified for each particular device structure. The clock and bias voltages required for high total dose operation of the devices are presented.

Omentin-1 levels are reduced by pharmacologic doses of leptin, but remain unaffected by energy deprivation and display no day-night variation.

PubMed

Hamnvik, Ole-Petter Riksfjord; Thakkar, Bindiya; Chamberland, John; Aronis, Konstantinos; Schneider, Benjamin; Mantzoros, Christos S

2015-02-01

To study the day-night variation of omentin-1 levels and assess whether leptin and/or short- and long-term energy deprivation alter circulating omentin-1 levels via cytokines. Omentin-1 levels were measured hourly in serum samples from six healthy men to evaluate for day-night variation. To study effects of acute energy deprivation and of leptin administration, eight healthy subjects were studied in the fasting state for 72 h with administration of either placebo or metreleptin (recombinant human leptin) in physiologic replacement doses. We evaluated the effect of leptin in pharmacologic doses on serum omentin-1 and cytokine levels, as well as on omentin-1 levels in ex vivo omental adipose tissue, in 15 healthy volunteers. To study the effect of chronic energy deprivation and weight loss on omentin-1 levels, we followed 18 obese subjects for 12 months who underwent bariatric surgery. There is no day-night variation in omentin-1 levels. Short-term and chronic energy deprivation, as well as ex vivo leptin administration and physiologic replacement doses of leptin, do not alter omentin-1 levels; pharmacologic doses of metreleptin reduce omentin-1 levels, whereas levels of tumor necrosis factor-α receptor II and interleukin-6 tend to increase. Omentin-1 levels are reduced by pharmacologic doses of metreleptin independent of effects on cytokine levels.

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats

PubMed Central

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-01-01

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. PMID:23698784

Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats.

PubMed

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-05-21

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.

2009-04-01

Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of thismore » study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome points were higher for the apex model compared with the non-apex model. Mean doses to the optimization points for both the cylinder models and all the cylinder diameters were 6 Gy, matching with the prescription dose of 6 Gy. Iterative optimization routine resulted in the highest dose to apex point and dome points. The mean dose for optimization point was 6.01 Gy for iterative optimization and was much higher than 5.74 Gy for geometric and equal times routines. Step size of 1 cm gave the highest dose to the apex point. This step size was superior in terms of mean dose to optimization points. Selection of dose optimization points for the derivation of optimized dose distributions for vaginal cylinders affects the dose distributions.« less

Evaluation of clinical use of OneDose™ metal oxide semiconductor field-effect transistor detectors compared to thermoluminescent dosimeters to measure skin dose for adult patients with acute lymphoblastic leukemia

PubMed Central

Al-Mohammed, Huda Ibrahim

2011-01-01

Background: Total body irradiation is a protocol used to treat acute lymphoblastic leukemia in patients prior to their bone marrow transplant. It involves the treatment of the whole body using a large radiation field with extended source-skin distance. Therefore, it is important to measure and monitor the skin dose during the treatment. Thermoluminescent dosimeters (TLDs) and the OneDose™ metal oxide semiconductor field effect transistor (MOSFET) detectors are used during treatment delivery to measure the radiation dose and compare it with the target prescribed dose. Aims: The primary goal of this study was to measure the variation of skin dose using OneDose MOSFET detectors and TLD detectors, and compare the results with the target prescribed dose. The secondary aim was to evaluate the simplicity of use and determine if one system was superior to the other in clinical use. Material and Methods: The measurements involved twelve adult patients diagnosed with acute lymphoblastic leukemia. TLD and OneDose MOSFET dosimetry were performed at ten different anatomical sites of each patient. Results: The results showed that there was a variation between skin dose measured with OneDose MOSFET detectors and TLD in all patients. However, the variation was not significant. Furthermore, the results showed for every anatomical site there was no significant different between the prescribed dose and the dose measured by either TLD or OneDose MOSFET detectors. Conclusion: There were no significant differences between the OneDose MOSFET and TLDs in comparison to the target prescribed dose. However, OneDose MOSFET detectors give a direct read-out immediately after the treatment, and their simplicity of use to compare with TLD detectors may make them preferred for clinical use. PMID:22171243

Aripiprazole Lauroxil

PubMed Central

Hard, Marjie L.; Mills, Richard J.; Sadler, Brian M.; Turncliff, Ryan Z.; Citrome, Leslie

2017-01-01

Abstract Background Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Methods Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. Findings The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. Conclusions This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice. PMID:28350572

Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid.

PubMed

Turolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, Andrea

2017-10-01

Peracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L -1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

PubMed

Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

2017-03-04

Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl 4 )-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl 4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl 4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl 4 -induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl 4 -induced liver damage in rats.

Evaluation of antipyretic potential of Vernonia cinerea extract in rats.

PubMed

Gupta, Malaya; Mazumder, U K; Manikandan, L; Bhattacharya, S; Haldar, P K; Roy, S

2003-08-01

The methanol extract of the whole plant of Vernonia cinerea (MEVC) was evaluated for its antipyretic potential on normal body temperature and yeast-induced pyrexia in rats. MEVC significantly reduced the normal body temperature at doses of 250 and 500 mg/kg body weight p.o. MEVC also lowered the elevated body temperature in the case of yeast-induced pyrexia in a dose dependent manner. The antipyretic effect of the extract at a dose of 500 mg/kg was identical to that of the standard drug paracetamol. Copyright 2003 John Wiley & Sons, Ltd.

SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patwe, P; Mhatre, V; Dandekar, P

Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

In vitro immunotoxicity assessment of culture-derived extracellular vesicles in human monocytes

PubMed Central

Rosas, Lucia E.; Elgamal, Ola A.; Mo, Xiaokui; Phelps, Mitch A.; Schmittgen, Thomas D.; Papenfuss, Tracey L.

2016-01-01

The potential to engineer extracellular vesicles (EV) that target specific cells and deliver a therapeutic payload has propelled a growing interest in their development as promising therapeutics. These EV are often produced from cultured cells. Very little is known about the interaction of cell culture-derived EV with cells of the immune system and their potential immunomodulatory effects. The present study evaluated potential immunotoxic effects of HEK293T-derived EV on the human monocytic cell lines THP-1 and U937. Incubation of cells with different doses of EV for 16–24 h was followed by assessment of cytotoxicity and cell function by flow cytometry. Changes in cell functionality were evaluated by the capacity of cells to phagocytize fluorescent microspheres. In addition, the internalization of labeled EV in THP-1 and U937 cells was evaluated. Exposure to EV did not affect the viability of THP-1 or U937 cells. Although lower doses of the EV increased phagocytic capacity in both cell lines, phagocytic efficiency of individual cells was not affected by EV exposure at any of the doses evaluated. This study also demonstrated that THP-1 and U937 monocytic cells are highly permissive to EV entry in a dose-response manner. These results suggest that, although HEK293T-derived EV are efficiently internalized by human monocytic cells, they do not exert a cytotoxic effect or alter phagocytic efficiency on the cell lines evaluated. PMID:27075513

Mammographic film-processor temperature, development time, and chemistry: effect on dose, contrast, and noise.

PubMed

Kimme-Smith, C; Rothschild, P A; Bassett, L W; Gold, R H; Moler, C

1989-01-01

Six different combinations of film-processor temperature (33.3 degrees C, 35 degrees C), development time (22 sec, 44 sec), and chemistry (Du Pont medium contrast developer [MCD] and Kodak rapid process [RP] developer) were each evaluated by separate analyses with Hurter and Driffield curves, test images of plastic step wedges, noise variance analysis, and phantom images; each combination also was evaluated clinically. Du Pont MCD chemistry produced greater contrast than did Kodak RP chemistry. A change in temperature from 33.3 degrees C (92 degrees F) to 35 degrees C (95 degrees F) had the least effect on dose and image contrast. Temperatures of 36.7 degrees C (98 degrees F) and 38.3 degrees C (101 degrees F) also were tested with extended processing. The speed increased for 36.7 degrees C but decreased at 38.3 degrees C. Base plus fog increased, but contrast decreased for these higher temperatures. Increasing development time had the greatest effect on decreasing the dose required for equivalent film darkening when imaging BR12 breast equivalent test objects; ion chamber measurements showed a 32% reduction in dose when the development time was increased from 22 to 44 sec. Although noise variance doubled in images processed with the extended development time, diagnostic capability was not compromised. Extending the processing time for mammographic films was an effective method of dose reduction, whereas varying the processing temperature and chemicals had less effect on contrast and dose.

Evaluation of indoor radon equilibrium factor using CFD modeling and resulting annual effective dose

NASA Astrophysics Data System (ADS)

Rabi, R.; Oufni, L.

2018-04-01

The equilibrium factor is an important parameter for reasonably estimating the population dose from radon. However, the equilibrium factor value depended mainly on the ventilation rate and the meteorological factors. Therefore, this study focuses on investigating numerically the influence of the ventilation rate, temperature and humidity on equilibrium factor between radon and its progeny. The numerical results showed that ventilation rate, temperature and humidity have significant impacts on indoor equilibrium factor. The variations of equilibrium factor with the ventilation, temperature and relative humidity are discussed. Moreover, the committed equivalent doses due to 218Po and 214Po radon short-lived progeny were evaluated in different tissues of the respiratory tract of the members of the public from the inhalation of indoor air. The annual effective dose due to radon short lived progeny from the inhalation of indoor air by the members of the public was investigated.

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

PubMed

Fernandez-Bañares, Fernando; Piqueras, Marta; Guagnozzi, Danila; Robles, Virginia; Ruiz-Cerulla, Alexandra; Casanova, María José; Gisbert, Javier P; Busquets, David; Arguedas, Yolanda; Pérez-Aisa, Angeles; Fernández-Salazar, Luis; Lucendo, Alfredo J

2017-09-01

Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

A comparative study for image quality and radiation dose of a cone beam computed tomography scanner and a multislice computed tomography scanner for paranasal sinus imaging.

PubMed

De Cock, Jens; Zanca, Federica; Canning, John; Pauwels, Ruben; Hermans, Robert

2015-07-01

To evaluate image quality and radiation dose of a state of the art cone beam computed tomography (CBCT) system and a multislice computed tomography (MSCT) system in patients with sinonasal poliposis. In this retrospective study two radiologists evaluated 57 patients with sinonasal poliposis who underwent a CBCT or MSCT sinus examination, along with a control group of 90 patients with normal radiological findings. Tissue doses were measured using a phantom model with thermoluminescent dosimeters (TLD). Overall image quality in CBCT was scored significantly higher than in MSCT in patients with normal radiologic findings (p-value: 0.00001). In patients with sinonasal poliposis, MSCT scored significantly higher than CBCT (p-value: 0.00001). The average effective dose for MSCT was 42% higher compared to CBCT (108 μSv vs 63 μSv). CBCT and MSCT are both suited for the evaluation of sinonasal poliposis. In patients with sinonasal poliposis, clinically important structures of the paranasal sinuses can be better delineated with MSCT, whereas in patients without sinonasal poliposis, CBCT turns out to define the important structures of the sinonasal region better. However, given the lower radiation dose, CBCT can be considered for the evaluation of the sinonasal structures in patients with sinonasal poliposis. • CBCT and MSCT are both suited for evaluation of sinonasal poliposis. • Effective dose for MSCT was 42% higher compared to CBCT. • In patients with sinonasal poliposis, clinically important anatomical structures are better delineated with MSCT. • In patients with normal radiological findings, clinically important anatomical structures are better delineated with CBCT.

Temporal resolution required for accurate evaluation of the interplay effect in spot scanning proton therapy

NASA Astrophysics Data System (ADS)

Seo, Jeongmin; Han, Min Cheol; Yeom, Yeon Soo; Lee, Hyun Su; Kim, Chan Hyeong; Jeong, Jong Hwi; Kim, SeongHoon

2017-04-01

In proton therapy, the spot scanning method is known to suffer from the interplay effect induced from the independent movements of the proton beam and the organs in the patient during the treatment. To study the interplay effect, several investigators have performed four-dimensional (4D) dose calculations with some limited temporal resolutions (4 or 10 phases per respiratory cycle) by using the 4D computed tomography (CT) images of the patient; however, the validity of the limited temporal resolutions has not been confirmed. The aim of the present study is to determine whether the previous temporal resolutions (4 or 10 phases per respiratory cycle) are really high enough for adequate study of the interplay effect in spot scanning proton therapy. For this study, a series of 4D dose calculations were performed with a virtual water phantom moving in the vertical direction during dose delivery. The dose distributions were calculated for different temporal resolutions (4, 10, 25, 50, and 100 phases per respiratory cycle), and the calculated dose distributions were compared with the reference dose distribution, which was calculated using an almost continuously-moving water phantom ( i.e., 1000 phases per respiratory cycle). The results of the present study show that the temporal resolutions of 4 and 10 phases per respiratory cycle are not high enough for an accurate evaluation of the interplay effect for spot scanning proton therapy. The temporal resolution should be at least 14 and 17 phases per respiratory cycle for 10-mm and 20-mm movement amplitudes, respectively, even for rigid movement ( i.e., without deformation) of the homogeneous water phantom considered in the present study. We believe that even higher temporal resolutions are needed for an accurate evaluation of the interplay effect in the human body, in which the organs are inhomogeneous and deform during movement.

Low dose evaluation of the antiandrogen flutamide following a Mode of Action approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarrabay, A.; UniverSud, INSERM, UMR-996 “Inflammation, Chemokines and Immunopathology”, Châtenay-Malabry; Bayer SAS, 16, rue Jean Marie Leclair, 69009 Lyon

ABSTRACT: The dose–response characterization of endocrine mediated toxicity is an on-going debate which is controversial when exploring the nature of the dose–response curve and the effect at the low-end of the curve. To contribute to this debate we have assessed the effects of a wide range of dose levels of the antiandrogen flutamide (FLU) on 7-week male Wistar rats. FLU was administered by oral gavage at doses of 0, 0.001, 0.01, 0.1, 1 and 10 mg/kg/day for 28 days. To evaluate the reproducibility, the study was performed 3 times. The molecular initiating event (MIE; AR antagonism), the key events (LHmore » increase, Leydig cell proliferation and hyperplasia increases) and associated events involved in the mode of action (MOA) of FLU induced testicular toxicity were characterized to address the dose response concordance. Results showed no effects at low doses (< 0.1 mg/kg/day) for the different key events studied. The histopathological changes (Leydig cell hyperplasia) observed at 1 and 10 mg/kg/day were associated with an increase in steroidogenesis gene expression in the testis from 1 mg/kg/day, as well as an increase in testosterone blood level at 10 mg/kg/day. Each key event dose–response was in good concordance with the MOA of FLU on the testis. From the available results, only monotonic dose–response curves were observed for the MIE, the key events, associated events and in effects observed in other sex related tissues. All the results, so far, show that the reference endocrine disruptor FLU induces threshold effects in a standard 28-day toxicity study on adult male rats. - Highlights: • Dose–response characterization of endocrine mediated toxicity is an on-going debate. • A wide range of dose levels of flutamide was evaluated on young adult male rats. • Flutamide induces threshold effects using on standard and molecular tools.« less

Evaluation of Kidney Stones with Reduced-Radiation Dose CT: Progress from 2011-2012 to 2015-2016-Not There Yet.

PubMed

Weisenthal, Karrin; Karthik, Priyadarshini; Shaw, Melissa; Sengupta, Debapriya; Bhargavan-Chatfield, Mythreyi; Burleson, Judy; Mustafa, Adel; Kalra, Mannudeep; Moore, Christopher

2018-02-01

Purpose To determine if the use of reduced-dose computed tomography (CT) for evaluation of kidney stones increased in 2015-2016 compared with that in 2011-2012, to determine variability in radiation exposure according to facility for this indication, and to establish a current average radiation dose for CT evaluation for kidney stones by querying a national dose registry. Materials and Methods This cross-sectional study was exempt from institutional review board approval. Data were obtained from the American College of Radiology dose registry for CT examinations submitted from July 2015 to June 2016. Study descriptors consistent with single-phase unenhanced CT for evaluation of kidney stones and associated RadLex® Playbook identifiers (RPIDs) were retrospectively identified. Facilities actively submitting data on kidney stone-specific CT examinations were included. Dose metrics including volumetric CT dose index, dose-length product, and size-specific dose estimate, when available, were reported, and a random effects model was run to account for clustering of CT examinations at facilities. A z-ratio was calculated to test for a significant difference between the proportion of reduced-radiation dose CT examinations (defined as those with a dose-length product of 200 mGy · cm or less) performed in 2015-2016 and the proportion performed in 2011-2012. Results Three hundred four study descriptors for kidney stone CT corresponding to data from 328 facilities that submitted 105 334 kidney stone CT examinations were identified. Reduced-dose CT examinations accounted for 8040 of 105 334 (7.6%) CT examinations, a 5.6% increase from the 1010 of 49 903 (2%) examinations in 2011-2012 (P < .001). Mean overall dose-length product was 689 mGy · cm (95% confidence interval: 667, 712), decreased from the mean of 746 mGy · cm observed in 2011-2012. Median facility dose-length product varied up to sevenfold, from less than 200 mGy · cm to greater than 1600 mGy · cm. Conclusion Use of reduced-radiation dose CT for evaluation of kidney stones has increased since 2011-2012, but remains low; variability of radiation dose according to facility continues to be wide. National mean CT radiation exposure for evaluation of renal colic during 2015-2016 decreased relative to 2011-2012 values, but remained well above what is reasonably achievable. © RSNA, 2017.

Mounting evidence indicates that escalating doses of allopurinol are unnecessary for cardiovascular protection: Comment on Coburn et al.

PubMed

Bredemeier, Markus

2018-05-09

We read with interest the study by Coburn et al. (1), a methodologically sound propensity-score matched cohort study evaluating the effect of dose escalation of allopurinol on cardiovascular (CV) and overall mortality. The results indicate that increasing doses carry a higher risk of mortality, but the authors comment that failure in achieving doses up to 600 mg may have contributed to the absence of protective effect. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of gamma irradiation on physical characteristics of Jordanian durum wheat and quality of semolina and lasagna products

NASA Astrophysics Data System (ADS)

Azzeh, F. S.; Amr, A. S.

2009-09-01

This study was conducted to determine the effect of using varying gamma irradiation doses on the physiochemical and rheological properties of semolina and its products. Ash, protein and water content were not influenced with gamma irradiation, while falling number and fungi counts decreased with increasing irradiation dose. Irradiation adversely affected wet gluten at 5 kGy dose. Dough stability was deteriorated vigorously with increasing irradiation dose. Sensory evaluation showed that lasagna produced from 0.25- and 1 kGy-irradiated semolina did not show any significant differences as compared with the control sample.

The Safety, Effectiveness and Concentrations of Adjusted Lopinavir/Ritonavir in HIV-Infected Adults on Rifampicin-Based Antitubercular Therapy

PubMed Central

Decloedt, Eric H.; Maartens, Gary; Smith, Peter; Merry, Concepta; Bango, Funeka; McIlleron, Helen

2012-01-01

Objective Rifampicin co-administration dramatically reduces plasma lopinavir concentrations. Studies in healthy volunteers and HIV-infected patients showed that doubling the dose of lopinavir/ritonavir (LPV/r) or adding additional ritonavir offsets this interaction. However, high rates of hepatotoxicity were observed in healthy volunteers. We evaluated the safety, effectiveness and pre-dose concentrations of adjusted doses of LPV/r in HIV infected adults treated with rifampicin-based tuberculosis treatment. Methods Adult patients on a LPV/r-based antiretroviral regimen and rifampicin-based tuberculosis therapy were enrolled. Doubled doses of LPV/r or an additional 300 mg of ritonavir were used to overcome the inducing effect of rifampicin. Steady-state lopinavir pre-dose concentrations were evaluated every second month. Results 18 patients were enrolled with a total of 79 patient months of observation. 11/18 patients were followed up until tuberculosis treatment completion. During tuberculosis treatment, the median (IQR) pre-dose lopinavir concentration was 6.8 (1.1–9.2) mg/L and 36/47 (77%) were above the recommended trough concentration of 1 mg/L. Treatment was generally well tolerated with no grade 3 or 4 toxicity: 8 patients developed grade 1 or 2 transaminase elevation, 1 patient defaulted additional ritonavir due to nausea and 1 patient developed diarrhea requiring dose reduction. Viral loads after tuberculosis treatment were available for 11 patients and 10 were undetectable. Conclusion Once established on treatment, adjusted doses of LPV/r co-administered with rifampicin-based tuberculosis treatment were tolerated and LPV pre-dose concentrations were adequate. PMID:22412856

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanck, Oliver, E-mail: oliver.blanck@uksh.de; CyberKnife Center Northern Germany, Guestrow; Bode, Frank

Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarringmore » of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.« less

Analgesic and anti-inflammatory activities of Piper nigrum L.

PubMed

Tasleem, Farhana; Azhar, Iqbal; Ali, Syed Nawazish; Perveen, Shaista; Mahmood, Zafar Alam

2014-09-01

To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships.

PubMed

Hartman, Rebecca L; Brown, Timothy L; Milavetz, Gary; Spurgin, Andrew; Gorelick, David A; Gaffney, Gary; Huestis, Marilyn A

2016-07-01

Vaporized cannabis and concurrent cannabis and alcohol intake are commonplace. We evaluated the subjective effects of cannabis, with and without alcohol, relative to blood and oral fluid (OF, advantageous for cannabis exposure screening) cannabinoid concentrations and OF/blood and OF/plasma vaporized-cannabinoid relationships. Healthy adult occasional-to-moderate cannabis smokers received a vaporized placebo or active cannabis (2.9% and 6.7% Δ(9) -tetrahydrocannabinol, THC) with or without oral low-dose alcohol (~0.065g/210L peak breath alcohol concentration [BrAC]) in a within-subjects design. Blood and OF were collected up to 8.3 h post-dose and subjective effects measured at matched time points with visual-analogue scales and 5-point Likert scales. Linear mixed models evaluated subjective effects by THC concentration, BrAC, and interactions. Effects by time point were evaluated by dose-wise analysis of variance (ANOVA). OF versus blood or plasma cannabinoid ratios and correlations were evaluated in paired-positive specimens. Nineteen participants (13 men) completed the study. Blood THC concentration or BrAC significantly associated with subjective effects including 'high', while OF contamination prevented significant OF concentration associations <1.4 h post-dose. Subjective effects persisted through 3.3-4.3 h, with alcohol potentiating the duration of the cannabis effects. Effect-versus-THC concentration and effect-versus-alcohol concentration hystereses were counterclockwise and clockwise, respectively. OF/blood and OF/plasma THC significantly correlated (all Spearman r≥0.71), but variability was high. Vaporized cannabis subjective effects were similar to those previously reported after smoking, with duration extended by concurrent alcohol. Cannabis intake was identified by OF testing, but OF concentration variability limited interpretation. Blood THC concentrations were more consistent across subjects and more accurate at predicting cannabis' subjective effects. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals.

PubMed

Kameswara Rao, B; Giri, R; Kesavulu, M M; Apparao, C

2001-01-01

The effect of administration of different doses of Pterocarpus santalinus L. bark extracts in normal and diabetic rats, on blood glucose levels was evaluated in this study. Among the three fractions (aqueous, ethanol and hexane), ethanolic fraction at the dose of 0.25 g/kg body weight showed maximum antihyperglycemic activity. The same dose did not cause any hypoglycemic activity in normal rats. The results were compared with the diabetic rats treated with glibenclamide and the antihyperglycemic activity of ethanolic extract of PS bark at the dose of 0.25 g/kg b.w. was found to be more effective than that of glibenclamide.

Evaluation of low-dose irradiation on microbiological quality of white carrots and string beans

NASA Astrophysics Data System (ADS)

Koike, Amanda C. R.; Santillo, Amanda G.; Rodrigues, Flávio T.; Duarte, Renato C.; Villavicencio, Anna Lucia C. H.

2012-08-01

The minimally processed food provided the consumer with a product quality, safety and practicality. However, minimal processing of food does not reduce pathogenic population of microorganisms to safe levels. Ionizing radiation used in low doses is effective to maintain the quality of food, reducing the microbiological load but rather compromising the nutritional values and sensory property. The association of minimal processing with irradiation could improve the quality and safety of product. The purpose of this study was to evaluate the effectiveness of low-doses of ionizing radiation on the reduction of microorganisms in minimally processed foods. The results show that the ionizing radiation of minimally processed vegetables could decontaminate them without several changes in its properties.

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biological end points were assessed; growth responses were the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude. The average low-dose maximum stimulation was approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hormetic curve approaching the estimated no observable effect level for the particular end point. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the hormetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitative scheme is presented for future application to the database. PMID:9539030

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Evaluation of the reinforcing and subjective effects of heroin in combination with dextromethorphan and quinidine

PubMed Central

Vosburg, Suzanne K.; Sullivan, Maria A.; Comer, Sandra D.

2015-01-01

Objective Studies have suggested that the N-methyl-d-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence. Design This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers. Participants Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days. Interventions Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants. Results Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving. Conclusions In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence. PMID:22320027

Novel, single-dose, topical treatment of tinea pedis using terbinafine: results of a dose-finding clinical trial.

PubMed

de Chauvin, Martine Feuilhade; Viguié-Vallanet, Claude; Kienzler, Jean-Luc; Larnier, Catherine

2008-01-01

Tinea pedis is the most common dermatophytosis requiring topical antifungals for at least 1-4 weeks. To determine the effectiveness of a novel topical single dose formulation of terbinafine (film forming solution-FFS) in the treatment of tinea pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria suffering from tinea pedis with possible extension to soles confirmed by mycological examination (direct and culture) were evaluated for efficacy of terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled parallel group dose finding study. Evaluations were carried out at baseline, 1 and 6 weeks after a single application of FFS. Effective treatment rate based on negative mycology (direct and culture) and minimal signs and symptoms (two or less with only mild recorded) was measured at week 6. Effective treatment rates at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with 18% with placebo. All three active preparations were shown to be significantly superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non-inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose for the treatment of tinea pedis. This novel product represents a significant advance with the enhanced compliance and convenience that it offers.

Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized, double-blinded, placebo-controlled study.

PubMed

Choi, Sun Young; Hong, Ji Yeon; Ko, Eun Jung; Kim, Beom Joon; Hong, Sung-Woon; Lim, Mi Hyoung; Yeon, Sung Hum; Son, Rak Ho

2018-02-01

Oxidative stress and photodamage resulting from ultraviolet radiation exposure play key roles in skin aging. Fermented Cyclopia intermedia, which is used to brew honeybush tea, exerts antioxidant and anti-wrinkle effects by inhibiting reactive oxygen species production and downregulating matrix metalloproteinase activity. This randomized, double-blinded, placebo-controlled study aimed to evaluate the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. 120 Korean subjects with crow's feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo (negative control, only dextran) for 12 weeks. Wrinkles were evaluated using JANUS ® and PRIMO pico ® . Skin elasticity, hydration and transepidermal water loss were measured. Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to placebo group, as well as for skin hydration and elasticity. Both the low- and high-dose groups showed significantly decreased TEWL compared to the placebo group. There were no adverse effects during the entire study period. Our data indicate that HU-018 is effective for improving skin wrinkles, elasticity, and hydration. Therefore, daily supplementation with fermented honeybush could be helpful for protecting against skin aging.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects

PubMed Central

Shinoda, Yasutaka; Kuroda, Ayaka; Yoshida, Aya; Mitsuoka, Machiko; Mori, Kouki; Kawachi, Yuki; Moriya, Akihiro; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

2018-01-01

Background Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Patients and Methods Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Results Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases (P < 0.01). One case (3%) of watery stool, one case of loose stools (3%), and no cases of abdominal pain (0%) were observed. Median defaecation frequencies in the high-dose group (7 and 9) were significantly higher than those in the low-dose group (4 and 3) in the first (P = 0.0133) and second (P = 0.0101) weeks, respectively. There was no significant change in clinical laboratory values. Conclusion We suggest that DKT increases defaecation frequency and is safe for treating constipation. PMID:29693001

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

Effectiveness of Jeryl Lynn-containing vaccine in Spanish children.

PubMed

Castilla, Jesús; García Cenoz, Manuel; Arriazu, Maite; Fernández-Alonso, Mirian; Martínez-Artola, Víctor; Etxeberria, Jaione; Irisarri, Fátima; Barricarte, Aurelio

2009-03-26

We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006-2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1-OR. Some 70% of cases had received one dose of measles-mumps-rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39-87%). Two doses were more effective (83%; 54-94%) than a single dose (66%; 25-85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR=3.1; 1.2-8.4) and those who had received the second dose 3 or more years before study enrolment (OR=10.2; 1.5-70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention.

Cost-effectiveness of Apixaban Compared With Edoxaban for Stroke Prevention in Nonvalvular Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Lanitis, Tereza; Kongnakorn, Thitima; Phatak, Hemant; Chalkiadaki, Corina; Liu, Xianchen; Kuznik, Andreas; Lawrence, Jack; Dorian, Paul

2015-11-01

The purpose of this analysis was to assess the cost-effectiveness of apixaban 5 mg BID versus high- and low-dose edoxaban (60 mg and 30 mg once daily) as intended starting dose strategies for stroke prevention in patients from a UK National Health Service perspective. A previously developed and validated Markov model was adapted to evaluate the lifetime clinical and economic impact of apixaban 5 mg BID versus edoxaban (high and low dose) in patients with nonvalvular atrial fibrillation. A pairwise indirect treatment comparison was conducted for clinical end points, and price parity was assumed between apixaban and edoxaban. Costs in 2012 British pounds, life-years, and quality-adjusted life-years (QALYs) gained, discounted at 3.5% per annum, were estimated. Apixaban was predicted to increase life expectancy and QALYs versus low- and high-dose edoxaban. These gains were achieved at cost-savings versus low-dose edoxaban, thus being dominant and nominal increases in costs versus high-dose edoxaban. The incremental cost-effectiveness ratio of apixaban versus high-dose edoxaban was £6763 per QALY gained. Apixaban was deemed to be dominant (less costly and more effective) versus low-dose edoxaban and a cost-effective alternative to high-dose edoxaban. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

PubMed

Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

2016-04-01

We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Generalised photon skyshine calculations.

PubMed

Hayes, Robert

2004-01-01

The energy-dependent dose contributions from monoenergetic photon source points located 1.5 m above the ground have been tabulated. These values are intended to be used for regulatory compliance with site boundary dose limitations and as such are all presented in effective dose units. Standard air and soil are modelled where the air has vertical density gradient approximation. Energies from 0.05 up to 10 MeV are evaluated for dose transport up to 40 mean free paths.

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

PubMed

Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

2017-09-23

Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P < 0.0001), female gender (P = 0.022), increased age (P = 0.048), and increased local anesthetic dose (P = 0.01). In a multivariable model, block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effect of compound Maqin decoction on TGF-β1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

PubMed

Xie, Y H; Li, X P; Xu, Z X; Qian, P; Li, X L; Wang, Y Q

2016-09-02

In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-β1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-β1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-β1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles.

PubMed

Xie, Shuyu; Wang, Fenghua; Wang, Yan; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Li, Xihe; Zhou, Wenzhong

2011-11-20

Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD(50)) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

PubMed Central

2011-01-01

Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity. PMID:22098626

Vertical Distribution and Estimated Doses from Artificial Radionuclides in Soil Samples around the Chernobyl Nuclear Power Plant and the Semipalatinsk Nuclear Testing Site

PubMed Central

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides (241Am, 134Cs, 137Cs, and 60Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides (241Am, 57Co, 137Cs, 95Zr, 95Nb, 58Co, and 60Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public. PMID:23469013

Vertical distribution and estimated doses from artificial radionuclides in soil samples around the Chernobyl nuclear power plant and the Semipalatinsk nuclear testing site.

PubMed

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides ((241)Am, (134)Cs, (137)Cs, and (60)Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides ((241)Am, (57)Co, (137)Cs, (95)Zr, (95)Nb, (58)Co, and (60)Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public.

PROPOSALS FOR THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR RADIOGRAPHY FOR ADULT PATIENTS BASED ON REGIONAL DOSE SURVEYS IN RUSSIAN FEDERATION.

PubMed

Vodovatov, A V; Balonov, M I; Golikov, V Yu; Shatsky, I G; Chipiga, L A; Bernhardsson, C

2017-04-01

In 2009-2014, dose surveys aimed to collect adult patient data and parameters of most common radiographic examinations were performed in six Russian regions. Typical patient doses were estimated for the selected examinations both in entrance surface dose and in effective dose. 75%-percentiles of typical patient effective dose distributions were proposed as preliminary regional diagnostic reference levels (DRLs) for radiography. Differences between the 75%-percentiles of regional typical patient dose distributions did not exceed 30-50% for the examinations with standardized clinical protocols (skull, chest and thoracic spine) and a factor of 1.5 for other examinations. Two different approaches for establishing national DRLs were evaluated: as a 75%-percentile of a pooled regional sample of patient typical doses (pooled method) and as a median of 75%-percentiles of regional typical patient dose distributions (median method). Differences between pooled and median methods for effective dose did not exceed 20%. It was proposed to establish Russian national DRLs in effective dose using a pooled method. In addition, the local authorities were granted an opportunity to establish regional DRLs if the local radiological practice and typical patient dose distributions are significantly different. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

PubMed

Li, Jun; Nekka, Fahima

2013-02-21

The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration

NASA Astrophysics Data System (ADS)

Hanlon, Justin Mitchell

Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose determined (0.29 mSv) is comparable to diagnostic procedures involving the head, such as an x-ray or CT scan. Thus, the computational assessment performed indicates that a previously established therapeutic dose can be delivered effectively to the macula with IRay(TM) without the potential for secondary complications.

SEMICONDUCTOR TECHNOLOGY: An efficient dose-compensation method for proximity effect correction

NASA Astrophysics Data System (ADS)

Ying, Wang; Weihua, Han; Xiang, Yang; Renping, Zhang; Yang, Zhang; Fuhua, Yang

2010-08-01

A novel simple dose-compensation method is developed for proximity effect correction in electron-beam lithography. The sizes of exposed patterns depend on dose factors while other exposure parameters (including accelerate voltage, resist thickness, exposing step size, substrate material, and so on) remain constant. This method is based on two reasonable assumptions in the evaluation of the compensated dose factor: one is that the relation between dose factors and circle-diameters is linear in the range under consideration; the other is that the compensated dose factor is only affected by the nearest neighbors for simplicity. Four-layer-hexagon photonic crystal structures were fabricated as test patterns to demonstrate this method. Compared to the uncorrected structures, the homogeneity of the corrected hole-size in photonic crystal structures was clearly improved.

A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.

PubMed

Breglia, Rudolph; Bui, Quang; Burnett, Donald; Koschier, Francis; Lapadula, Elizabeth; Podhasky, Paula; Schreiner, Ceinwen; White, Russell

2014-01-01

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

Evaluation of the annual Canadian biodosimetry network intercomparisons

PubMed Central

Wilkins, Ruth C.; Beaton-Green, Lindsay A.; Lachapelle, Sylvie; Kutzner, Barbara C.; Ferrarotto, Catherine; Chauhan, Vinita; Marro, Leonora; Livingston, Gordon K.; Boulay Greene, Hillary; Flegal, Farrah N.

2015-01-01

Abstract Purpose: To evaluate the importance of annual intercomparisons for maintaining the capacity and capabilities of a well-established biodosimetry network in conjunction with assessing efficient and effective analysis methods for emergency response. Materials and methods: Annual intercomparisons were conducted between laboratories in the Canadian National Biological Dosimetry Response Plan. Intercomparisons were performed over a six-year period and comprised of the shipment of 10–12 irradiated, blinded blood samples for analysis by each of the participating laboratories. Dose estimates were determined by each laboratory using the dicentric chromosome assay (conventional and QuickScan scoring) and where possible the cytokinesis block micronucleus (CBMN) assay. Dose estimates were returned to the lead laboratory for evaluation and comparison. Results: Individual laboratories performed comparably from year to year with only slight fluctuations in performance. Dose estimates using the dicentric chromosome assay were accurate about 80% of the time and the QuickScan method for scoring the dicentric chromosome assay was proven to reduce the time of analysis without having a significant effect on the dose estimates. Although analysis with the CBMN assay was comparable to QuickScan scoring with respect to speed, the accuracy of the dose estimates was greatly reduced. Conclusions: Annual intercomparisons are necessary to maintain a network of laboratories for emergency response biodosimetry as they evoke confidence in their capabilities. PMID:25670072

Experimental evaluation of a MOSFET dosimeter for proton dose measurements.

PubMed

Kohno, Ryosuke; Nishio, Teiji; Miyagishi, Tomoko; Hirano, Eriko; Hotta, Kenji; Kawashima, Mitsuhiko; Ogino, Takashi

2006-12-07

The metal oxide semiconductor field-effect transistor (MOSFET) dosimeter has been widely studied for use as a dosimeter for patient dose verification. The major advantage of this detector is its size, which acts as a point dosimeter, and also its ease of use. The commercially available TN502RD MOSFET dosimeter manufactured by Thomson and Nielsen has never been used for proton dosimetry. Therefore we used the MOSFET dosimeter for the first time in proton dose measurements. In this study, the MOSFET dosimeter was irradiated with 190 MeV therapeutic proton beams. We experimentally evaluated dose reproducibility, linearity, fading effect, beam intensity dependence and angular dependence for the proton beam. Furthermore, the Bragg curve and spread-out Bragg peak were also measured and the linear-energy transfer (LET) dependence of the MOSFET response was investigated. Many characteristics of the MOSFET response for proton beams were the same as those for photon beams reported in previous papers. However, the angular MOSFET responses at 45, 90, 135, 225, 270 and 315 degrees for proton beams were over-responses of about 15%, and moreover the MOSFET response depended strongly on the LET of the proton beam. This study showed that the angular dependence and LET dependence of the MOSFET response must be considered very carefully for quantitative proton dose evaluations.

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Stewart, Nicholas; Freeborn, Danielle L.

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects),more » singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics differed with acute and repeated administration.« less

Effective doses and organ doses in the MIRD-5 phantom exposed to monoenergetic 0.1 MeV to 200 MeV electrons in the LAT direction.

PubMed

Katagiri, M; Hikoji, M; Kitaichi, M; Aoki, Y; Sawamura, S

2001-01-01

Organ doses and effective doses were calculated using the EGS-4 Monte Carlo simulation code and a MIRD-5 mathematical human phantom placed in a vacuum. For broad right and left lateral beams of monoenergetic (0.1-200 MeV) electrons, conversion coefficients from the incident fluence to organ dose, to effective dose, and to effective dose equivalent were obtained. There were no clear differences between the conversion coefficients in the case of left-lateral (LLAT) and right-lateral (RLAT) irradiation. Therefore, when investigating lateral geometries for electron exposure, it is not necessary to evaluate both directions independently. In general, conversion coefficients for lateral irradiation (LAT) were smaller than those for AP and PA. The difference between the AP and PA conversion coefficients and LAT became smaller with increasing incident energy; at 200 MeV the conversion coefficients were almost independent of the irradiation geometry. The agreement between the results of the present study and those of other studies was acceptable within the statistical uncertainties.

Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens.

PubMed Central

Tinwell, Helen; Ashby, John

2004-01-01

We have evaluated whether mixtures of estrogens, present in the mix at doses that are individually inactive in the immature rat uterotrophic assay, can give a uterotrophic response. Seven chemicals were evaluated: nonylphenol, bisphenol A (BPA), methoxychlor, genistein (GEN), estradiol, diethylstilbestrol, and ethinyl estradiol. Dose responses in the uterotrophic assay were constructed for each chemical. The first series of experiments involved evaluating binary mixtures of BPA and GEN at dose levels that gave moderate uterotrophic responses when tested individually. The mixtures generally showed an intermediate or reduced uterotrophic effect compared with when the components of the mixture were tested alone at the dose used in the mixture. The next series of experiments used a multicomponent (complex) mixture of all seven chemicals evaluated at doses that gave either weakly positive or inactive uterotrophic responses when tested individually in the assay. Doses that were nominally equi-uterotrophic ranged over approximately six orders of magnitude for the seven chemicals. Doses of agents that gave a weak uterotrophic response when tested individually gave a marginally enhanced positive response in the assay when tested combined as a mixture. Doses of agents that gave a negative uterotrophic response when tested individually gave a positive response when tested as a mixture. These data indicate that a variety of different estrogen receptor (ER) agonists, present individually at subeffective doses, can act simultaneously to evoke an ER-regulated response. However, translating these findings into the process of environmental hazard assessment will be difficult. The simple addition of the observed, or predicted, activities for the components of a mixture is confirmed here to be inappropriate and to overestimate the actual effect induced by the mixture. Equally, isobole analysis is only suitable for two- or three-component mixtures, and concentration addition requires access to dose-response data and EC50 values (concentration giving 50% of the maximum response) for the individual components of the mixture--requirements that will rarely be fulfilled for complex environmental samples. Given these uncertainties, we conclude that it may be most expedient to select and bioassay whole environmental mixtures of potential concern. PMID:15064164

Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors.

PubMed

Hosoya, Kenji; Couto, C Guillermo; London, Cheryl A; Kisseberth, William C; Phelps, Mitchell A; Dalton, James T

2014-01-01

To evaluate the clinical toxicity and activity of orally administered artemisinin in dogs with spontaneous tumors, 24 client-owned dogs were randomly divided into two groups and received either low-continuous dose (3 mg/kg q 24 hr) or high-dose intermittent (three doses of 45 mg/kg q 6 hr repeated q 1 wk) of artemisinin per os. Treatment was continued for 21 days. Dogs were evaluated weekly for clinical effect and at the end of the treatment for hematologic and biochemical adverse events. Whole blood concentrations of artemisinin and dihydroartemisinin were measured by liquid chromatography/tandem mass spectrometry after the first dose of artemisinin in three dogs in each group. Blood concentrations of artemisinin and dihydroartemisinin were <0.1 μM at all time points, and there was no difference in blood concentration between the two dosing groups. The most frequent adverse event was anorexia, which was observed in 11% of the low-dose group and 29% of the high-dose group. Oral artemisinin, both in low-dose continuous and high-dose intermittent, is well tolerated in dogs but results in low bioavailability. Parenteral administration should be considered for future studies.

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

PubMed

Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Turncliff, Ryan Z; Citrome, Leslie

2017-06-01

Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

Evaluation of the Pharmacokinetics and Efficacy of a Busulfan Test Dose in Adult Patients Undergoing Myeloablative Hematopoietic Cell Transplantation.

PubMed

Weil, Elizabeth; Zook, Felicia; Oxencis, Carolyn; Canadeo, Angela; Urmanski, Angela; Waggoner, Mindy; Eastwood, Daniel; Pasquini, Marcelo; Hamadani, Mehdi; Hari, Parameswaran

2017-06-01

Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Dose perturbations due to in vivo dosimetry with diodes.

PubMed

Alecu, R; Feldmeier, J J; Alecu, M

1997-03-01

In vivo dosimetry performed with semiconductor detectors is a reliable method for patient dose control. The purpose of this study is to evaluate the perturbations introduced in the patient's absorbed dose distribution by three types of commercially available diodes (Isorad, Sun Nuclear Corp.; model 114200, 114300 and 114400) from the same company and to present possible solutions for minimizing this side-effect.

Effect of gamma irradiation on the thiamine, riboflavin and vitamin B 6 content in two varieties of Brazilian beans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H. A. L. C. H.; Mancini-Filho, J. J.; Delincée, H. H.; Bognár, A. A.

2000-03-01

The effect of 60Co gamma rays on the content of several B-vitamins in two varieties of Brazilian beans has been studied. Carioca ( Phaseolus vulgaris L. var. Carioca) and Macaçar beans ( Vigna unguiculata L. Walp, var. Macaçar) were irradiated at doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy, and subsequently stored at ambient temperature for 6 months. The content of vitamin B 1, B 2 and B 6 was analysed by HPLC. In addition, the optimum cooking time was established for each dose and bean variety. A taste panel evaluated sensory properties. Only slight changes were measured for thiamine and riboflavin, whereas a dose-dependent decrease was noted for pyridoxine, which, however, was significant only at the highest doses of 5 and 10 kGy. Cooking time was considerably reduced with increasing radiation dose, but accompanied by a loss of the sensory quality. However, at the disinfestation dose up to 1 kGy, acceptable ratings were obtained for the sensory evaluation. In conclusion, for insect disinfestation of Brazilian beans radiation processing is a promising technology.

Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone.

PubMed

Roshanpour, Maryam; Ghasemi, Mehdi; Riazi, Kiarash; Rafiei-Tabatabaei, Neda; Ghahremani, Mohammad Hossein; Dehpour, Ahmad Reza

2009-02-01

The present study evaluated the development of tolerance to the anticonvulsant effect of morphine in a mouse model of clonic seizures induced by pentylenetetrazole, and whether ultra-low doses of the opioid receptor antagonist naltrexone which selectively block G(s) opioid receptors were capable of preventing the observed tolerance. The results showed that the morphine anticonvulsant effect could be subject to tolerance after repeated administration. Both the development and expression of tolerance were inhibited by ultra-low doses of naltrexone, suggesting the possible involvement of G(s)-coupled opioid receptors in the development of tolerance to the anticonvulsant effect of morphine.

Effective and safe mannitol administration in patients undergoing supratentorial tumor surgery: A prospective, randomized and double blind study.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Karabulut, Esra Sultan; Koksal, Serdar Selcuk; Altindas, Fatis; Tunali, Yusuf

2017-08-01

Although osmotic diuresis with mannitol is commonly used to provide brain relaxation, there is no consensus regarding its optimal dose and combination with loop diuretics. The aim of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity in patients undergoing supratentorial tumor surgery. This prospective, randomized, double blind, placebo-controlled study included 51 patients (ASA I-III) scheduled for elective supratentorial craniotomy. Different doses and combinations of diuretics were administered after the bone flap removal. The Group 1 received mannitol at 0.5gkg -1 and furosemide at 0.5mgkg -1 , the Group 2 received mannitol at 1gkg -1 and furosemide at 0.5mgkg -1 , and the Group 3 received mannitol at 0.5gkg -1 and placebo. The primary end-point of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and the secondary end-points are to evaluate their effects on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity. This study shows that mannitol alone (0.5gkg -1 ), and the combinations of furosemide (0.5mgkg -1 ) with different doses of mannitol (0.5gkg -1 -1gkg -1 ) provides adequate brain relaxation. However, administration of furosemide with low or high doses of mannitol may cause reduction in the sodium and chloride levels as well as rise in the lactate level. Moreover it may cause high urine output and negative intra-operative fluid balance. Administration of 0.5gkg -1 mannitol provides adequate brain relaxation without causing systemic side effects in patients undergoing supratentorial tumor surgery. This study is registered to clinical trials (Clinical Trials.gov identifier NCT02712476). Copyright © 2017 Elsevier B.V. All rights reserved.

EFFECT OF RADIATION DOSE LEVEL ON ACCURACY AND PRECISION OF MANUAL SIZE MEASUREMENTS IN CHEST TOMOSYNTHESIS EVALUATED USING SIMULATED PULMONARY NODULES

PubMed Central

Söderman, Christina; Johnsson, Åse Allansdotter; Vikgren, Jenny; Norrlund, Rauni Rossi; Molnar, David; Svalkvist, Angelica; Månsson, Lars Gunnar; Båth, Magnus

2016-01-01

The aim of the present study was to investigate the dependency of the accuracy and precision of nodule diameter measurements on the radiation dose level in chest tomosynthesis. Artificial ellipsoid-shaped nodules with known dimensions were inserted in clinical chest tomosynthesis images. Noise was added to the images in order to simulate radiation dose levels corresponding to effective doses for a standard-sized patient of 0.06 and 0.04 mSv. These levels were compared with the original dose level, corresponding to an effective dose of 0.12 mSv for a standard-sized patient. Four thoracic radiologists measured the longest diameter of the nodules. The study was restricted to nodules located in high-dose areas of the tomosynthesis projection radiographs. A significant decrease of the measurement accuracy and intraobserver variability was seen for the lowest dose level for a subset of the observers. No significant effect of dose level on the interobserver variability was found. The number of non-measurable small nodules (≤5 mm) was higher for the two lowest dose levels compared with the original dose level. In conclusion, for pulmonary nodules at positions in the lung corresponding to locations in high-dose areas of the projection radiographs, using a radiation dose level resulting in an effective dose of 0.06 mSv to a standard-sized patient may be possible in chest tomosynthesis without affecting the accuracy and precision of nodule diameter measurements to any large extent. However, an increasing number of non-measurable small nodules (≤5 mm) with decreasing radiation dose may raise some concerns regarding an applied general dose reduction for chest tomosynthesis examinations in the clinical praxis. PMID:26994093

EFFECT OF RADIATION DOSE LEVEL ON ACCURACY AND PRECISION OF MANUAL SIZE MEASUREMENTS IN CHEST TOMOSYNTHESIS EVALUATED USING SIMULATED PULMONARY NODULES.

PubMed

Söderman, Christina; Johnsson, Åse Allansdotter; Vikgren, Jenny; Norrlund, Rauni Rossi; Molnar, David; Svalkvist, Angelica; Månsson, Lars Gunnar; Båth, Magnus

2016-06-01

The aim of the present study was to investigate the dependency of the accuracy and precision of nodule diameter measurements on the radiation dose level in chest tomosynthesis. Artificial ellipsoid-shaped nodules with known dimensions were inserted in clinical chest tomosynthesis images. Noise was added to the images in order to simulate radiation dose levels corresponding to effective doses for a standard-sized patient of 0.06 and 0.04 mSv. These levels were compared with the original dose level, corresponding to an effective dose of 0.12 mSv for a standard-sized patient. Four thoracic radiologists measured the longest diameter of the nodules. The study was restricted to nodules located in high-dose areas of the tomosynthesis projection radiographs. A significant decrease of the measurement accuracy and intraobserver variability was seen for the lowest dose level for a subset of the observers. No significant effect of dose level on the interobserver variability was found. The number of non-measurable small nodules (≤5 mm) was higher for the two lowest dose levels compared with the original dose level. In conclusion, for pulmonary nodules at positions in the lung corresponding to locations in high-dose areas of the projection radiographs, using a radiation dose level resulting in an effective dose of 0.06 mSv to a standard-sized patient may be possible in chest tomosynthesis without affecting the accuracy and precision of nodule diameter measurements to any large extent. However, an increasing number of non-measurable small nodules (≤5 mm) with decreasing radiation dose may raise some concerns regarding an applied general dose reduction for chest tomosynthesis examinations in the clinical praxis. © The Author 2016. Published by Oxford University Press.

Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

PubMed

Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

2016-01-01

The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

Space radiation risk limits and Earth-Moon-Mars environmental models

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Hu, Shaowen; Schwadron, Nathan A.; Kozarev, K.; Townsend, Lawrence W.; Kim, Myung-Hee Y.

2010-12-01

We review NASA's short-term and career radiation limits for astronauts and methods for their application to future exploration missions outside of low Earth orbit. Career limits are intended to restrict late occurring health effects and include a 3% risk of exposure-induced death from cancer and new limits for central nervous system and heart disease risks. Short-term dose limits are used to prevent in-flight radiation sickness or death through restriction of the doses to the blood forming organs and to prevent clinically significant cataracts or skin damage through lens and skin dose limits, respectively. Large uncertainties exist in estimating the health risks of space radiation, chiefly the understanding of the radiobiology of heavy ions and dose rate and dose protraction effects, and the limitations in human epidemiology data. To protect against these uncertainties NASA estimates the 95% confidence in the cancer risk projection intervals as part of astronaut flight readiness assessments and mission design. Accurate organ dose and particle spectra models are needed to ensure astronauts stay below radiation limits and to support the goal of narrowing the uncertainties in risk projections. Methodologies for evaluation of space environments, radiation quality, and organ doses to evaluate limits are discussed, and current projections for lunar and Mars missions are described.

Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract of Leonotis ocymifolia (Burm.f.) Iwarsson Leaves in Rodent Models

PubMed Central

Alemu, Asnakech

2018-01-01

Background Pain and inflammation are the major health problems commonly treated with traditional remedies mainly using medicinal plants. Leonotis ocymifolia is one of such medicinal plants used in folkloric medicine of Ethiopia. However, the plant has not been scientifically evaluated. The aim of this study was to evaluate analgesic and anti-inflammatory effects of the 80% methanol leaves extract of Leonotis ocymifolia using rodent models. Method The central and peripheral analgesic effect of the extract at 100, 200, and 400 mg/kg dose levels was evaluated using hot plate and acetic acid induced writhing rodent models, whereas carrageenan induced paw edema and cotton pellet granuloma methods were used to screen anti-inflammatory effect of the extract at the same dose levels. Acute toxicity test was also done. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test and p < 0.05 was considered significant. Results The extract did not produce mortality up to 2000 mg/kg. All tested doses of the extract showed significant analgesic effect with maximum latency response of 62.8% and inhibition of acetic acid induced writhing. Maximum anti-inflammatory effect was recorded at 6 h after induction, with 75.88% reduction in carrageenan induced paw edema. Moreover, all tested doses of extract significantly inhibited the formation of inflammatory exudates and granuloma formation (p < 0.001). Conclusion The study indicated that the extract was safe in mice and it has both analgesic and anti-inflammatory effect in rodent models. PMID:29675050

Effect of multiple honey doses on non-specific acute cough in children. An open randomised study and literature review.

PubMed

Miceli Sopo, S; Greco, M; Monaco, S; Varrasi, G; Di Lorenzo, G; Simeone, G

2015-01-01

Honey is recommended for non-specific acute paediatric cough by the Australian guidelines. Current available randomised clinical trials evaluated the effects of a single evening dose of honey, but multiple doses outcomes have never been studied. To evaluate the effects of wildflower honey, given for three subsequent evenings, on non-specific acute paediatric cough, compared to dextromethorphan (DM) and levodropropizine (LDP), which are the most prescribed over-the-counter (OTC) antitussives in Italy. 134 children suffering from non-specific acute cough were randomised to receive for three subsequent evenings a mixture of milk (90ml) and wildflower honey (10ml) or a dose of DM or LDP adjusted for the specific age. The effectiveness was evaluated by a cough questionnaire answered by parents. Primary end-point efficacy was therapeutic success. The latter was defined as a decrease in cough questionnaire score greater than 50% after treatment compared with baseline values. Three children were excluded from the study, as their parents did not complete the questionnaire. Therapeutic success was achieved by 80% in the honey and milk group and 87% in OTC medication group (p=0.25). Milk and honey mixture seems to be at least as effective as DM or LDP in non-specific acute cough in children. These results are in line with previous studies, which reported the health effects of honey on paediatric cough, even if placebo effect cannot be totally excluded. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

Investigation of dose characteristics in three-dimensional MAGAT-type polymer gel dosimetry with MSE MR imaging

NASA Astrophysics Data System (ADS)

Lee, Jason J. S.; Tsai, Chia-Jung; Lo, Man-Kuok; Huang, Yung-Hui; Chen, Chien-Chuan; Wu, Jay; Tyan, Yeu-Sheng; Wu, Tung-Hsin

2008-05-01

A new type of normoxic polymer gel dosimeter, named MAGAT responses well to absorbed dose even when manufacturing in the presence of normal levels of oxygen. The aim of this study was to evaluate dose response, diffusion effect and cumulated dose response under multiple fractional irradiations of the MAGAT gel dosimeter using Multiple Spin-Echo (MSE) Magnetic Resonance (MR) sequence. Dose response was performed by irradiating MAGAT-gel-filled testing vials with a 6 MV linear accelerator and a linear relationship was present with doses from 0 to 6 Gy, but gradually, a bi-exponential function result was obtained with given doses up to 20 Gy. No significant difference in dose response was present between single and cumulated doses (p > 0.05). For study of diffusion effect, edge sharpness of the R2 map imaging between two split doses was smaller than 1 cm of dose profile penumbra between 20% and 80%. In conclusion, the MAGAT polymer gel dosimeter with MSE MR imaging is a promising method for dose verification in clinical radiation therapy practice.

Is the use of the cervical vertebrae maturation method justified to determine skeletal age? A comparison of radiation dose of two strategies for skeletal age estimation.

PubMed

Patcas, Raphael; Signorelli, Luca; Peltomäki, Timo; Schätzle, Marc

2013-10-01

The aim of this study was to assess effective doses of a lateral cephalogram radiograph with and without thyroid shield and compare the differences with the radiation dose of a hand-wrist radiograph. Thermoluminescent dosimeters were placed at 19 different sites in the head and neck of a tissue-equivalent human skull (RANDO phantom). Analogue lateral cephalograms with and without thyroid shield (67 kV, 250 mA, 10 mAs) and hand-wrist radiographs (40 kV, 250 mA, 10 mAs) were obtained. The effective doses were calculated using the 2007 International Commission on Radiological Protection recommendations. The effective dose for conventional lateral cephalogram without a thyroid shield was 5.03 microsieverts (µSv). By applying a thyroid shield to the RANDO phantom, a remarkable dose reduction of 1.73 µSv could be achieved. The effective dose of a conventional hand-wrist radiograph was calculated to be 0.16 µSv. Adding the effective dose of the hand-wrist radiograph to the effective dose of the lateral cephalogram with thyroid shield resulted in a cumulative effective dose of 3.46 µSv. Without thyroid shield, the effective dose of a lateral cephalogram was approximately 1.5-fold increased than the cumulative effective dose of a hand-wrist radiograph and a lateral cephalogram with thyroid shield. Thyroid is an organ that is very sensitive to radiation exposure. Its shielding will significantly reduce the effective dose. An additional hand-wrist radiograph, involving no vulnerable tissues, however, causes very little radiation risk. In accordance with the ALARA (As Low As Reasonably Achievable) principle, if an evaluation of skeletal age is indicated, an additional hand-wrist radiograph seems much more justifiable than removing the thyroid shield.

Evaluation of the low dose cardiac CT imaging using ASIR technique

NASA Astrophysics Data System (ADS)

Fan, Jiahua; Hsieh, Jiang; Deubig, Amy; Sainath, Paavana; Crandall, Peter

2010-04-01

Today Cardiac imaging is one of the key driving forces for the research and development activities of Computed Tomography (CT) imaging. It requires high spatial and temporal resolution and is often associated with high radiation dose. The newly introduced ASIR technique presents an efficient method that offers the dose reduction benefits while maintaining image quality and providing fast reconstruction speed. This paper discusses the study of image quality of the ASIR technique for Cardiac CT imaging. Phantoms as well as clinical data have been evaluated to demonstrate the effectiveness of ASIR technique for Cardiac CT applications.

Surfactant-Enhanced Desorption and Biodegradation of Polycyclic Aromatic Hydrocarbons in Contaminated Soil

PubMed Central

Zhu, Hongbo; Aitken, Michael D.

2010-01-01

We evaluated two nonionic surfactants, one hydrophobic (Brij 30) and one hydrophilic (C12E8), for their ability to enhance the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil after it had been treated in an aerobic bioreactor. The effects of each surfactant were evaluated at doses corresponding to equilibrium aqueous-phase concentrations well above the surfactant’s critical micelle concentration (CMC), slightly above the CMC, and below the CMC. The concentrations of all 3- and 4-ring PAHs were significantly lower in the soil amended with Brij 30 at the two lower doses compared to controls, whereas removal of only the 3-ring PAHs was significantly enhanced at the highest Brij 30 dose. In contrast, C12E8 did not enhance PAH removal at any dose. In the absence of surfactant, <5% of any PAH desorbed from the soil over an 18-d period. Brij 30 addition at the lowest dose significantly increased the desorption of most PAHs, whereas the addition of C12E8 at the lowest dose actually decreased the desorption of all PAHs. These findings suggest that the effects of the two surfactants on PAH biodegradation could be explained by their effects on PAH bioavailability. Overall, this study demonstrates that the properties of the surfactant and its dose relative to the corresponding aqueous-phase concentration are important factors in designing systems for surfactant-enhanced bioremediation of PAH-contaminated soils in which PAH bioavailability is limited. PMID:20586488

Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.

PubMed

Kara, Murat; Yumrutas, Onder; Demir, Caner F; Ozdemir, Hasan Huseyin; Bozgeyik, Ibrahim; Coskun, Salih; Eraslan, Ersen; Bal, Ramazan

2015-10-01

The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions.

PubMed

Weaver, James L; Tobin, Grainne A; Ingle, Taylor; Bancos, Simona; Stevens, David; Rouse, Rodney; Howard, Kristina E; Goodwin, David; Knapton, Alan; Li, Xiaohong; Shea, Katherine; Stewart, Sharron; Xu, Lin; Goering, Peter L; Zhang, Qin; Howard, Paul C; Collins, Jessie; Khan, Saeed; Sung, Kidon; Tyner, Katherine M

2017-07-17

As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages. Repeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested. The clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.

Evaluation of growth hormone treatment efficacy in short Japanese children born small for gestational age: Five-year treatment outcome and impact on puberty

PubMed Central

Horikawa, Reiko; Tanaka, Toshiaki; Nishinaga, Hiromi; Ogawa, Yoshihisa; Yokoya, Susumu

2017-01-01

Abstract. Some children born small for gestational age (SGA) have short stature and are at an increased risk of developing psychosocial or behavioral problems. Here we evaluated the efficacy of GH and its effects on the timing of pubertal onset in a 3-yr extension of our previous 2-yr (total 5 yr) multicenter, randomized, double-blind, parallel-group clinical trial of 65 short Japanese children born SGA. Patients received low or high doses of GH (0.033 or 0.067 mg/kg/day, respectively). Age at onset of puberty was not statistically different for male and female patients receiving high- or low-dose GH. After the onset of puberty, no difference in height gain was observed between the two GH dose groups. At the onset of puberty, height standard deviation scores for chronological age of boys and girls improved significantly in both dose groups with evidence of a dose-response effect. Mean bone age/chronological age ratios in the low- and high-dose groups were significantly increased compared with baseline, being significantly greater in the high-dose group at 5 yr after treatment initiation. Delayed bone age at baseline was close to chronological age following GH treatment. GH treatment, especially high-dose GH, induced advanced bone age in short children born SGA. PMID:28458458

Dental flat panel conebeam CT in the evaluation of patients with inflammatory sinonasal disease: Diagnostic efficacy and radiation dose savings.

PubMed

Leiva-Salinas, C; Flors, L; Gras, P; Más-Estellés, F; Lemercier, P; Patrie, J T; Wintermark, M; Martí-Bonmatí, L

2014-01-01

CT is the imaging modality of choice to study the paranasal sinuses; unfortunately, it involves significant radiation dose. Our aim was to assess the diagnostic validity, image quality, and radiation-dose savings of dental conebeam CT in the evaluation of patients with suspected inflammatory disorders of the paranasal sinuses. We prospectively studied 40 patients with suspected inflammatory disorders of the sinuses with dental conebeam CT and standard CT. Two radiologists analyzed the images independently, blinded to clinical information. The image quality of both techniques and the diagnostic validity of dental conebeam CT compared with the reference standard CT were assessed by using 3 different scoring systems. Image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated for both techniques. The absorbed radiation dose to the lenses and thyroid and parotid glands was measured by using a phantom and dosimeter chips. The effective radiation dose for CT was calculated. All dental conebeam CT scans were judged of diagnostic quality. Compared with CT, the conebeam CT image noise was 37.3% higher (P < .001) and the SNR of the bone was 75% lower (P < .001). The effective dose of our conebeam CT protocol was 23 μSv. Compared with CT, the absorbed radiation dose to the lenses and parotid and thyroid glands with conebeam CT was 4%, 7.8%, and 7.3% of the dose delivered to the same organs by conventional CT (P < .001). Dental conebeam CT is a valid imaging procedure for the evaluation of patients with inflammatory sinonasal disorders. © 2014 by American Journal of Neuroradiology.

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain from Spinal Cord Injury and Disease

PubMed Central

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-01-01

Using eight hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, the majority of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta-9-tetrahydrocannabinol on three separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was utilized to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model demonstrated a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (e.g., good drug effect, feeling high, etc.) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all p<0.0004). Psychoactive and subjective effects were dose dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. As the two active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. PMID:27286745

Evaluation of On-Board kV Cone Beam Computed Tomography–Based Dose Calculation With Deformable Image Registration Using Hounsfield Unit Modifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onozato, Yusuke; Kadoya, Noriyuki, E-mail: kadoya.n@rad.med.tohoku.ac.jp; Fujita, Yukio

2014-06-01

Purpose: The purpose of this study was to estimate the accuracy of the dose calculation of On-Board Imager (Varian, Palo Alto, CA) cone beam computed tomography (CBCT) with deformable image registration (DIR), using the multilevel-threshold (MLT) algorithm and histogram matching (HM) algorithm in pelvic radiation therapy. Methods and Materials: One pelvis phantom and 10 patients with prostate cancer treated with intensity modulated radiation therapy were studied. To minimize the effect of organ deformation and different Hounsfield unit values between planning CT (PCT) and CBCT, we modified CBCT (mCBCT) with DIR by using the MLT (mCBCT{sub MLT}) and HM (mCBCT{sub HM})more » algorithms. To evaluate the accuracy of the dose calculation, we compared dose differences in dosimetric parameters (mean dose [D{sub mean}], minimum dose [D{sub min}], and maximum dose [D{sub max}]) for planning target volume, rectum, and bladder between PCT (reference) and CBCTs or mCBCTs. Furthermore, we investigated the effect of organ deformation compared with DIR and rigid registration (RR). We determined whether dose differences between PCT and mCBCTs were significantly lower than in CBCT by using Student t test. Results: For patients, the average dose differences in all dosimetric parameters of CBCT with DIR were smaller than those of CBCT with RR (eg, rectum; 0.54% for DIR vs 1.24% for RR). For the mCBCTs with DIR, the average dose differences in all dosimetric parameters were less than 1.0%. Conclusions: We evaluated the accuracy of the dose calculation in CBCT, mCBCT{sub MLT}, and mCBCT{sub HM} with DIR for 10 patients. The results showed that dose differences in D{sub mean}, D{sub min}, and D{sub max} in mCBCTs were within 1%, which were significantly better than those in CBCT, especially for the rectum (P<.05). Our results indicate that the mCBCT{sub MLT} and mCBCT{sub HM} can be useful for improving the dose calculation for adaptive radiation therapy.« less

Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions.

PubMed

Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M; Ricoul, Michelle; Sabatier, Laure

2016-01-01

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term "relative dose effect" (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy.

Potential Interference of Oil Vehicles on Genital Tubercle Development during the Fetal Period in ICR Mice.

PubMed

Nishioka, Yasushi; Tamai, Kazuki; Onda, Masanari; Hiromori, Youhei; Kimura, Tomoki; Hu, Jianying; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2018-01-01

Corn oil, sesame oil, and 10% ethanol in corn oil are commonly used as dosing vehicles in toxicology studies. Since these vegetable oils contain bioactive compounds, it is important for toxicology studies to characterize the toxicities of the dosing vehicles themselves. It has been recently proposed that the width of the genital tubercle (GT), the dorsal-ventral length (D-V length) of the GT, and urethral tube closure in mouse fetuses can be used as novel markers for monitoring sexual development in mice. However, how these parameters are influenced by the dosing vehicles themselves remains unclear. Therefore, we evaluated the effects of corn oil, sesame oil, and 10% ethanol in corn oil on GT width, D-V length, and GT morphology in ICR mice. Our results showed that all three vehicles influenced GT width and D-V length, but not GT morphology, suggesting that the effects of dosing vehicles themselves might need to be considered when GT width or D-V length is used as a parameter to evaluate the effects of chemicals on GT development.

Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of Δ9-THC in cannabis users

PubMed Central

Lile, Joshua A.; Kelly, Thomas H.; Charnigo, Richard J.; Stinchcomb, Audra L.; Hays, Lon R.

2013-01-01

Oral Δ9-tetrahydrocannabinol (Δ9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral Δ9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral Δ9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. Δ9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug- sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral Δ9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral Δ9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response. PMID:23754596

INSREC: Computational System for Quantitative Analysis of Radiation Effects Covering All Radiation Field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong Hoon Shin; Young Wook Lee; Young Ho Cho

2006-07-01

In the nuclear energy field, there are so many difficult things that even people who are working in this field are not much familiar with, such as, Dose evaluation, Dose management, etc. Thus, so many efforts have been done to achieve the knowledge and data for understanding. Although some data had been achieved, the applications of these data to necessary cases were more difficult job. Moreover, the type of Dose evaluation program until now was 'Console type' which is not easy enough to use for the beginners. To overcome the above causes of difficulties, the window-based integrated program and databasemore » management were developed in our research lab. The program, called as INSREC, consists of four sub-programs as follow; INSREC-NOM, INSREC-ACT, INSREC-MED, and INSREC-EXI. In ICONE 11 conference, INSREC-program(ICONE-36203) which can evaluates on/off-site dose of nuclear power plant in normal operation was introduced. Upgraded INSREC-program which will be presented in ICONE 14 conference has three additional codes comparing with pre-presented INSREC-program. Those subprograms can evaluate on/off-site Dose of nuclear power plant in accident cases. And they also have the functions of 'Dose evaluation and management' in the hospital and provide the 'Expert system' based on knowledge related to nuclear energy/radiation field. The INSREC-NOM, one of subprograms, is composed of 'Source term evaluation program', 'Atmospheric diffusion factor evaluation program', 'Off-site dose evaluation program', and 'On-site database program'. The INSREC-ACT is composed of 'On/Off-site dose evaluation program' and 'Result analysis program' and the INSREC-MED is composed of 'Workers/patients dose database program' and 'Dose evaluation program for treatment room'. The final one, INSREC-EXI, is composed of 'Database searching program based on artificial intelligence', 'Instruction program,' and 'FAQ/Q and A boards'. Each program was developed by using of Visual C++, Microsoft Access mainly. To verify the reliability, some suitable programs were selected such as AZAP and Stardose programs for the comparison. The AZAP program was selected for the on/off-site dose evaluation during the normal operation of nuclear reactor and Stardose program was used for the on/off-site dose evaluation in accident. The MCNP code was used for the dose evaluation and management in the hospital. Each comparison result was acceptable in errors analysis. According to the reliable verification results, it was concluded that INSREC program had an acceptable reliability for dose calculation and could give many proper dada for the sites. To serve the INSREC to people, the proper server system was constructed. We gave chances for the people (user) to utilize the INSREC through network connected to server system. The reactions were pretty much good enough to be satisfied. For the future work, many efforts will be given to improve the better user-interface and more necessary data will be provided to more people through database supplement and management. (authors)« less

Neurogenic Effects of Low-Dose Whole-Body HZE (Fe) Ion and Gamma Irradiation.

PubMed

Sweet, Tara B; Hurley, Sean D; Wu, Michael D; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

2016-12-01

Understanding the dose-toxicity profile of radiation is critical when evaluating potential health risks associated with natural and man-made sources in our environment. The purpose of this study was to evaluate the effects of low-dose whole-body high-energy charged (HZE) iron (Fe) ions and low-energy gamma exposure on proliferation and differentiation of adult-born neurons within the dentate gyrus of the hippocampus, cells deemed to play a critical role in memory regulation. To determine the dose-response characteristics of the brain to whole-body Fe-ion vs. gamma-radiation exposure, C57BL/6J mice were irradiated with 1 GeV/n Fe ions or a static 137 Cs source (0.662 MeV) at doses ranging from 0 to 300 cGy. The neurogenesis was analyzed at 48 h and one month postirradiation. These experiments revealed that whole-body exposure to either Fe ions or gamma radiation leads to: 1. An acute decrease in cell division within the dentate gyrus of the hippocampus, detected at doses as low as 30 and 100 cGy for Fe ions and gamma radiation, respectively; and 2. A reduction in newly differentiated neurons (DCX immunoreactivity) at one month postirradiation, with significant decreases detected at doses as low as 100 cGy for both Fe ions and gamma rays. The data presented here contribute to our understanding of brain responses to whole-body Fe ions and gamma rays and may help inform health-risk evaluations related to systemic exposure during a medical or radiologic/nuclear event or as a result of prolonged space travel.

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.

PubMed

Shin, Dongseong; Lee, SeungHwan; Yi, Sojeong; Yoon, Seo Hyun; Cho, Joo-Youn; Bahng, Mi Young; Jang, In-Jin; Yu, Kyung-Sang

2017-01-01

DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized C max and AUC 0- t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.

Anti-Emetic Drug Effects on Pilot Performance, Phase 2: Simulation Test.

DTIC Science & Technology

1996-04-01

The objectives of this study were to evaluate the effects of two anti-emetic drugs, granisetron (2 mg oral dose) and ondansetron (8 mg oral dose), on...and preduce no cognitive, psychomotor or subjective state changes. In this study, there was no evidence of performance degradation caused by either granisetron or ondansetron when tested in a complex military task environment.

Radiosensitivity study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju

NASA Astrophysics Data System (ADS)

Rashid, Rosnani Abdul; Daud, Fauzi; Senafi, Sahidan; Awang, Mat Rasol; Mohamad, Azhar; Mutaat, Hassan Hamdani; Maskom, Mohd Meswan

2014-09-01

Radiosensitive dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec-1. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The radiosensitivity study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD50 to be equal at 2.2 kGy. The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.

Natural radioactivity measurements and dosimetric evaluations in soil samples with a high content of NORM

NASA Astrophysics Data System (ADS)

Caridi, F.; Marguccio, S.; Durante, G.; Trozzo, R.; Fullone, F.; Belvedere, A.; D'Agostino, M.; Belmusto, G.

2017-01-01

In this article natural radioactivity measurements and dosimetric evaluations in soil samples contaminated by Naturally Occurring Radioactive Materials (NORM) are made, in order to assess any possible radiological hazard for the population and for workers professionally exposed to ionizing radiations. Investigated samples came from the district of Crotone, Calabria region, South of Italy. The natural radioactivity investigation was performed by high-resolution gamma-ray spectrometry. From the measured gamma spectra, activity concentrations were determined for 226Ra , 234-mPa , 224Ra , 228Ac and 40K and compared with their clearance levels for NORM. The total effective dose was calculated for each sample as due to the committed effective dose for inhalation and to the effective dose from external irradiation. The sum of the total effective doses estimated for all investigated samples was compared to the action levels provided by the Italian legislation (D.Lgs.230/95 and subsequent modifications) for the population members (0.3mSv/y) and for professionally exposed workers (1mSv/y). It was found to be less than the limit of no radiological significance (10μSv/y).

Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

PubMed

Abdolmaleki, Arash; Moghimi, Ali; Ghayour, Mohammad B; Rassouli, Morteza B

2016-10-15

Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (P<0.05). Citicoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (P<0.05). Additionally, citicoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (P<0.05). The pentobarbital induced sleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect. Copyright © 2016 Elsevier B.V. All rights reserved.

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

PubMed

Thorn, M C; Kelly, M; Rees, J H; Sánchez-Friera, P; Calvez, M

2002-09-01

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

Clinical trial with Secnidazole in a single dose in Venezuelan children infected by Giardia intestinalis.

PubMed

Di Prisco, M C; Jiménez, J C; Rodríguez, N; Costa, V; Villamizar, J; Silvera, A; Carrillo, M; Lira, C; Zerpa, E; López, Y

2000-09-01

The aim of this work was to evaluate in an open, noncomparative study the use of secnidazole in oral suspension given to Venezuelan children infected with Giardia intestinalis, from a community in Carapita, a slum area in Caracas. Seventy children from 2 to 11 years old (38 males and 32 females) were treated with a single oral dose of secnidazole (30 mg/Kg of body weight), after clinical and parasitological evaluation to make the diagnosis of active giardiasis. The effectiveness of treatment was determined by clinical examination and parasitological evaluation of feces samples 15 days after treatment. The results showed 95% of clinical cure with a significant decrease of the frequency of gastrointestinal symptoms. The parasitological cure was 98%, there were 4 failures at the end of treatment. Side effects observed after treatment were of mild intensity, lasting only few hours. These results show that a simple dose of secnidazole in an oral suspension is an effective, safe and well tolerated treatment for giardiasis in children and that this drug may be used as a mass treatment in risk populations.

Dose estimation for astronauts using dose conversion coefficients calculated with the PHITS code and the ICRP/ICRU adult reference computational phantoms.

PubMed

Sato, Tatsuhiko; Endo, Akira; Sihver, Lembit; Niita, Koji

2011-03-01

Absorbed-dose and dose-equivalent rates for astronauts were estimated by multiplying fluence-to-dose conversion coefficients in the units of Gy.cm(2) and Sv.cm(2), respectively, and cosmic-ray fluxes around spacecrafts in the unit of cm(-2) s(-1). The dose conversion coefficients employed in the calculation were evaluated using the general-purpose particle and heavy ion transport code system PHITS coupled to the male and female adult reference computational phantoms, which were released as a common ICRP/ICRU publication. The cosmic-ray fluxes inside and near to spacecrafts were also calculated by PHITS, using simplified geometries. The accuracy of the obtained absorbed-dose and dose-equivalent rates was verified by various experimental data measured both inside and outside spacecrafts. The calculations quantitatively show that the effective doses for astronauts are significantly greater than their corresponding effective dose equivalents, because of the numerical incompatibility between the radiation quality factors and the radiation weighting factors. These results demonstrate the usefulness of dose conversion coefficients in space dosimetry. © Springer-Verlag 2010

Impact of Spot Size and Spacing on the Quality of Robustly Optimized Intensity Modulated Proton Therapy Plans for Lung Cancer.

PubMed

Liu, Chenbin; Schild, Steven E; Chang, Joe Y; Liao, Zhongxing; Korte, Shawn; Shen, Jiajian; Ding, Xiaoning; Hu, Yanle; Kang, Yixiu; Keole, Sameer R; Sio, Terence T; Wong, William W; Sahoo, Narayan; Bues, Martin; Liu, Wei

2018-06-01

To investigate how spot size and spacing affect plan quality, robustness, and interplay effects of robustly optimized intensity modulated proton therapy (IMPT) for lung cancer. Two robustly optimized IMPT plans were created for 10 lung cancer patients: first by a large-spot machine with in-air energy-dependent large spot size at isocenter (σ: 6-15 mm) and spacing (1.3 σ), and second by a small-spot machine with in-air energy-dependent small spot size (σ: 2-6 mm) and spacing (5 mm). Both plans were generated by optimizing radiation dose to internal target volume on averaged 4-dimensional computed tomography scans using an in-house-developed IMPT planning system. The dose-volume histograms band method was used to evaluate plan robustness. Dose evaluation software was developed to model time-dependent spot delivery to incorporate interplay effects with randomized starting phases for each field per fraction. Patient anatomy voxels were mapped phase-to-phase via deformable image registration, and doses were scored using in-house-developed software. Dose-volume histogram indices, including internal target volume dose coverage, homogeneity, and organs at risk (OARs) sparing, were compared using the Wilcoxon signed-rank test. Compared with the large-spot machine, the small-spot machine resulted in significantly lower heart and esophagus mean doses, with comparable target dose coverage, homogeneity, and protection of other OARs. Plan robustness was comparable for targets and most OARs. With interplay effects considered, significantly lower heart and esophagus mean doses with comparable target dose coverage and homogeneity were observed using smaller spots. Robust optimization with a small spot-machine significantly improves heart and esophagus sparing, with comparable plan robustness and interplay effects compared with robust optimization with a large-spot machine. A small-spot machine uses a larger number of spots to cover the same tumors compared with a large-spot machine, which gives the planning system more freedom to compensate for the higher sensitivity to uncertainties and interplay effects for lung cancer treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Post-column infusion study of the 'dosing vehicle effect' in the liquid chromatography/tandem mass spectrometric analysis of discovery pharmacokinetic samples.

PubMed

Shou, Wilson Z; Naidong, Weng

2003-01-01

It has become increasingly popular in drug development to conduct discovery pharmacokinetic (PK) studies in order to evaluate important PK parameters of new chemical entities (NCEs) early in the discovery process. In these studies, dosing vehicles are typically employed in high concentrations to dissolve the test compounds in dose formulations. This can pose significant problems for the liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis of incurred samples due to potential signal suppression of the analytes caused by the vehicles. In this paper, model test compounds in rat plasma were analyzed using a generic fast gradient LC/MS/MS method. Commonly used dosing vehicles, including poly(ethylene glycol) 400 (PEG 400), polysorbate 80 (Tween 80), hydroxypropyl beta-cyclodextrin, and N,N-dimethylacetamide, were fortified into rat plasma at 5 mg/mL before extraction. Their effects on the sample analysis results were evaluated by the method of post-column infusion. Results thus obtained indicated that polymeric vehicles such as PEG 400 and Tween 80 caused significant suppression (> 50%, compared with results obtained from plasma samples free from vehicles) to certain analytes, when minimum sample cleanup was used and the analytes happened to co-elute with the vehicles. Effective means to minimize this 'dosing vehicle effect' included better chromatographic separations, better sample cleanup, and alternative ionization methods. Finally, a real-world example is given to illustrate the suppression problem posed by high levels of PEG 400 in sample analysis, and to discuss steps taken in overcoming the problem. A simple but effective means of identifying a 'dosing vehicle effect' is also proposed. Copyright 2003 John Wiley & Sons, Ltd.

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

PubMed Central

2011-01-01

Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin. PMID:21466682

Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: studies using medium to high doses in animal models.

PubMed

López-Cruz, Laura; Pardo, Marta; Salamone, John D; Correa, Mercè

2014-08-15

Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for A1 and A2A receptors, which are colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses. Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses. Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas. Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

USDA-ARS?s Scientific Manuscript database

Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

Humic acid effect on catalase activity and the generation of reactive oxygen species in corn (Zea mays).

PubMed

Cordeiro, Flávio Couto; Santa-Catarina, Claudete; Silveira, Vanildo; de Souza, Sonia Regina

2011-01-01

Humic acids (HAs) have positive effects on plant physiology, but the molecular mechanisms underlying these events are only partially understood. The induction of root growth and emission of lateral roots (LRs) promoted by exogenous auxin is a natural phenomenon. Exogenous auxins are also associated with HA. Gas nitric oxide (NO) is a secondary messenger produced endogenously in plants. It is associated with metabolic events dependent on auxin. With the application of auxin, NO production is significantly increased, resulting in positive effects on plant physiology. Thus it is possible to evaluate the beneficial effects of the application of HA as an effect of auxin. To investigate the effects of HA the parameters of root growth, Zea mays was studied by evaluating the application of 3 mM C L⁻¹ of HA extracted from Oxisol and 100 µM SNP (sodium nitroprusside) and the NO donor, subject to two N-NO₃⁻, high dose (5.0 mM N-NO₃⁻) and low dose (5.0 mM N-NO₃⁻). Treatments with HA and NO were positively increased, regardless of the N-NO₃⁻ taken, as assessed by fresh weight and dry root, issue of LRs. The effects were more pronounced in the treatment with a lower dose of N-NO₃⁻. Detection of reactive oxygen species (ROS) in vivo and catalase activity were evaluated; these tests were associated with root growth. Under application of the bioactive substances tested, detection of ROS and catalase activity increased, especially in treatments with lower doses of N-NO₃⁻. The results of this experiment indicate that the effects of HA are dependent on ROS generation, which act as a messenger that induces root growth and the emission of LRs.

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Image quality in low-dose coronary computed tomography angiography with a new high-definition CT scanner.

PubMed

Kazakauskaite, Egle; Husmann, Lars; Stehli, Julia; Fuchs, Tobias; Fiechter, Michael; Klaeser, Bernd; Ghadri, Jelena R; Gebhard, Catherine; Gaemperli, Oliver; Kaufmann, Philipp A

2013-02-01

A new generation of high definition computed tomography (HDCT) 64-slice devices complemented by a new iterative image reconstruction algorithm-adaptive statistical iterative reconstruction, offer substantially higher resolution compared to standard definition CT (SDCT) scanners. As high resolution confers higher noise we have compared image quality and radiation dose of coronary computed tomography angiography (CCTA) from HDCT versus SDCT. Consecutive patients (n = 93) underwent HDCT, and were compared to 93 patients who had previously undergone CCTA with SDCT matched for heart rate (HR), HR variability and body mass index (BMI). Tube voltage and current were adapted to the patient's BMI, using identical protocols in both groups. The image quality of all CCTA scans was evaluated by two independent readers in all coronary segments using a 4-point scale (1, excellent image quality; 2, blurring of the vessel wall; 3, image with artefacts but evaluative; 4, non-evaluative). Effective radiation dose was calculated from DLP multiplied by a conversion factor (0.014 mSv/mGy × cm). The mean image quality score from HDCT versus SDCT was comparable (2.02 ± 0.68 vs. 2.00 ± 0.76). Mean effective radiation dose did not significantly differ between HDCT (1.7 ± 0.6 mSv, range 1.0-3.7 mSv) and SDCT (1.9 ± 0.8 mSv, range 0.8-5.5 mSv; P = n.s.). HDCT scanners allow low-dose 64-slice CCTA scanning with higher resolution than SDCT but maintained image quality and equally low radiation dose. Whether this will translate into higher accuracy of HDCT for CAD detection remains to be evaluated.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Alan J.; Vora, Nayana; Suh, Steve

2015-04-01

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 secondsmore » after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V{sub 45} {sub Gy}, V{sub 30} {sub Gy}, and V{sub 20} {sub Gy} organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.« less

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

PubMed

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD 50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

PubMed Central

Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

2011-01-01

Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

Dose-distance metric that predicts late rectal bleeding in patients receiving radical prostate external-beam radiotherapy

NASA Astrophysics Data System (ADS)

Lee, Richard; Chan, Elisa K.; Kosztyla, Robert; Liu, Mitchell; Moiseenko, Vitali

2012-12-01

The relationship between rectal dose distribution and the incidence of late rectal complications following external-beam radiotherapy has been previously studied using dose-volume histograms or dose-surface histograms. However, they do not account for the spatial dose distribution. This study proposes a metric based on both surface dose and distance that can predict the incidence of rectal bleeding in prostate cancer patients treated with radical radiotherapy. One hundred and forty-four patients treated with radical radiotherapy for prostate cancer were prospectively followed to record the incidence of grade ≥2 rectal bleeding. Radiotherapy plans were used to evaluate a dose-distance metric that accounts for the dose and its spatial distribution on the rectal surface, characterized by a logistic weighting function with slope a and inflection point d0. This was compared to the effective dose obtained from dose-surface histograms, characterized by the parameter n which describes sensitivity to hot spots. The log-rank test was used to determine statistically significant (p < 0.05) cut-off values for the dose-distance metric and effective dose that predict for the occurrence of rectal bleeding. For the dose-distance metric, only d0 = 25 and 30 mm combined with a > 5 led to statistical significant cut-offs. For the effective dose metric, only values of n in the range 0.07-0.35 led to statistically significant cut-offs. The proposed dose-distance metric is a predictor of rectal bleeding in prostate cancer patients treated with radiotherapy. Both the dose-distance metric and the effective dose metric indicate that the incidence of grade ≥2 rectal bleeding is sensitive to localized damage to the rectal surface.

Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

PubMed

Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

2015-01-01

The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was α<0.05. There was significant statistical difference between the study groups and the control group regarding the parameters of propofol injection pain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PubMed

Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

2008-10-01

This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

SU-E-T-318: The Effect of Patient Positioning Errors On Target Coverage and Cochlear Dose in Stereotactic Radiosurgery Treatment of Acoustic Neuromas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dellamonica, D.; Luo, G.; Ding, G.

Purpose: Setup errors on the order of millimeters may cause under-dosing of targets and significant changes in dose to critical structures especially when planning with tight margins in stereotactic radiosurgery. This study evaluates the effects of these types of patient positioning uncertainties on planning target volume (PTV) coverage and cochlear dose for stereotactic treatments of acoustic neuromas. Methods: Twelve acoustic neuroma patient treatment plans were retrospectively evaluated in Brainlab iPlan RT Dose 4.1.3. All treatment beams were shaped by HDMLC from a Varian TX machine. Seven patients had planning margins of 2mm, five had 1–1.5mm. Six treatment plans were createdmore » for each patient simulating a 1mm setup error in six possible directions: anterior-posterior, lateral, and superiorinferior. The arcs and HDMLC shapes were kept the same for each plan. Change in PTV coverage and mean dose to the cochlea was evaluated for each plan. Results: The average change in PTV coverage for the 72 simulated plans was −1.7% (range: −5 to +1.1%). The largest average change in coverage was observed for shifts in the patient's superior direction (−2.9%). The change in mean cochlear dose was highly dependent upon the direction of the shift. Shifts in the anterior and superior direction resulted in an average increase in dose of 13.5 and 3.8%, respectively, while shifts in the posterior and inferior direction resulted in an average decrease in dose of 17.9 and 10.2%. The average change in dose to the cochlea was 13.9% (range: 1.4 to 48.6%). No difference was observed based on the size of the planning margin. Conclusion: This study indicates that if the positioning uncertainty is kept within 1mm the setup errors may not result in significant under-dosing of the acoustic neuroma target volumes. However, the change in mean cochlear dose is highly dependent upon the direction of the shift.« less

Selective enhancement of fentanyl-induced antinociception by the delta agonist SNC162 but not by ketamine in rhesus monkeys: Further evidence supportive of delta agonists as candidate adjuncts to mu opioid analgesics.

PubMed

Banks, Matthew L; Folk, John E; Rice, Kenner C; Negus, S Stevens

2010-12-01

Mu-opioid receptor agonists such as fentanyl are effective analgesics, but their clinical use is limited by untoward effects. Adjunct medications may improve the effectiveness and/or safety of opioid analgesics. This study compared interactions between fentanyl and either the noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine or the delta-opioid receptor agonist SNC162 [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-phenyl)methyl]-N,N-diethylbenzamide] in two behavioral assays in rhesus monkeys. An assay of thermal nociception evaluated tail-withdrawal latencies from water heated to 50 and 54°C. An assay of schedule-controlled responding evaluated response rates maintained under a fixed-ratio 30 schedule of food presentation. Effects of each drug alone and of three mixtures of ketamine+fentanyl (22:1, 65:1, 195:1 ketamine/fentanyl) or SNC162+fentanyl (59:1, 176:1, 528:1 SNC162/fentanyl) were evaluated in each assay. All drugs and mixtures dose-dependently decreased rates of food-maintained responding, and drug proportions in the mixtures were based on relative potencies in this assay. Ketamine and SNC162 were inactive in the assay of thermal antinociception, but fentanyl and all mixtures produced dose-dependent antinociception. Drug interactions were evaluated using dose-addition and dose-ratio analysis. Dose-addition analysis revealed that interactions for all ketamine/fentanyl mixtures were additive in both assays. SNC162/fentanyl interactions were usually additive, but one mixture (176:1) produced synergistic antinociception at 50°C. Dose-ratio analysis indicated that ketamine failed to improve the relative potency of fentanyl to produce antinociception vs. rate suppression, whereas two SNC162/fentanyl mixtures (59:1 and 176:1) increased the relative potency of fentanyl to produce antinociception. These results suggest that delta agonists may produce more selective enhancement than ketamine of mu agonist-induced antinociception. Copyright © 2010 Elsevier Inc. All rights reserved.

Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

PubMed

Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

2014-10-01

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

THE CHALLENGE OF CIEMAT INTERNAL DOSIMETRY SERVICE FOR ACCREDITATION ACCORDING TO ISO/IEC 17025 STANDARD, FOR IN VIVO AND IN VITRO MONITORING AND DOSE ASSESSMENT OF INTERNAL EXPOSURES.

PubMed

Lopez, M A; Martin, R; Hernandez, C; Navarro, J F; Navarro, T; Perez, B; Sierra, I

2016-09-01

The accreditation of an Internal Dosimetry Service (IDS) according to ISO/IEC 17025 Standard is a challenge. The aim of this process is to guarantee the technical competence for the monitoring of radionuclides incorporated in the body and for the evaluation of the associated committed effective dose E(50). This publication describes the main accreditation issues addressed by CIEMAT IDS regarding all the procedures involving good practice in internal dosimetry, focussing in the difficulties to ensure the traceability in the whole process, the appropriate calculation of detection limit of measurement techniques, the validation of methods (monitoring and dose assessments), the description of all the uncertainty sources and the interpretation of monitoring data to evaluate the intake and the committed effective dose. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of GaAs low noise and power MMIC technologies to neutron, ionizing dose and dose rate effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Derewonko, H.; Bosella, A.; Pataut, G.

1996-06-01

An evaluation program of Thomson CSF-TCS GaAs low noise and power MMIC technologies to 1 MeV equivalent neutron fluence levels, up to 1 {times} 10{sup 15} n/cm{sup 2}, ionizing 1.17--1.33 MeV CO{sup 60} dose levels in excess of 200 Mrad(GaAs) and dose rate levels reaching 1.89 {times} 10{sup 11} rad(GaAs)/s is presented in terms of proper components and parameter choices, DC/RF electrical measurements and test methods under irradiation. Experimental results are explained together with drift analyses of electrical parameters that have determined threshold limits of component degradations. Modelling the effects of radiation on GaAs components relies on degradation analysis ofmore » active layer which appears to be the most sensitive factor. MMICs degradation under neutron fluence was simulated from irradiated FET data. Finally, based on sensitivity of technological parameters, rad-hard design including material, technology and MMIC design enhancement is discussed.« less

Body size-adjusted dose analysis of pirfenidone in patients with interstitial pneumonia.

PubMed

Uehara, Masahiro; Enomoto, Noriyuki; Oyama, Yoshiyuki; Suzuki, Yuzo; Kono, Masato; Furuhashi, Kazuki; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Suda, Takafumi

2018-03-01

Pirfenidone is an effective anti-fibrotic agent for idiopathic pulmonary fibrosis (IPF). Although adverse events (AE) sometimes prevent patients from continuing treatment, current dose adjustment guidance does not consider patient body size or weight (BW). The aim of this study was to evaluate the importance of pirfenidone dose adjustment by body surface area (BSA) or BW for preventing AE and permitting continuous treatment in patients with interstitial pneumonia (IP). Sixty-seven Japanese patients with IP including 46 patients with IPF treated with pirfenidone between 2009 and 2015 were retrospectively evaluated. Pirfenidone doses were adjusted by BSA or BW and were compared with clinical parameters. Forty-two of 67 patients (62.7%) with IP showed AE, most commonly gastrointestinal symptoms (77.5%). Patients having AE received significantly higher adjusted doses of pirfenidone by both BSA and BW (P = 0.024 and P = 0.010, respectively), while unadjusted doses did not differ. BSA-adjusted dose discriminated patients with AE from those without (area under the curve = 0.666 at 1085 mg/m 2 ). Six of seven patients (85.7%) who discontinued pirfenidone due to AE took ≥1085 mg/m 2 of pirfenidone. In a subgroup with IPF, patients taking a medium dose (median: 876 median-1085 mg/m 2 ) showed a lower annual decline in % forced vital capacity than patients taking a lower dose (P = 0.025). BSA-adjusted pirfenidone dosing may be useful to prevent AE whilst achieving a long-term treatment effect in patients with IP. © 2017 Asian Pacific Society of Respirology.

Pain and anxiety and their relationship with medication doses in the intensive care unit.

PubMed

Park, Sunyoung; Na, Se Hee; Oh, Jooyoung; Lee, Jong Seok; Oh, Seung-Taek; Kim, Jae-Jin; Park, Jin Young

2018-06-02

Pain and anxiety are understudied despite their importance to the general medical condition. The aim of the present study was to examine the effects of pain and anxiety and their relationship to the doses of opioids and anxiolytics administered in intensive care unit (ICU) patients. The subjects included 1349 conscious, critically ill patients admitted to an ICU. Psychiatrists evaluated the patients daily for pain and anxiety. Data regarding the doses of opioids and benzodiazepines administered were gathered. Linear mixed model was used for analysis. The pain and anxiety experienced by patients in the ICU were significantly correlated. Pain had significant main effects on the dose of opioids administered. No significant effects of anxiety on the daily dose of anxiolytics or opioids given were detected. Due to their closely linked relationship, pain and anxiety, can affect one another, and one can influence the other to appear more severe. In addition, anxiety can be underestimated in ICU patients. The present study suggests the need for precise evaluation and a comprehensive approach to the management of pain and anxiety. In addition, this study implies that management of anxiety may affect pain reduction, given the close correlation between the two. Copyright © 2018 Elsevier Inc. All rights reserved.

Fundamental Flaws of Hormesis for Public Health Decisions

PubMed Central

Thayer, Kristina A.; Melnick, Ronald; Burns, Kathy; Davis, Devra; Huff, James

2005-01-01

Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to promote the notion that while high-level exposures to toxic chemicals could be detrimental to human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive, generalizable phenomenon and argue that the default assumption for risk assessments should be that toxic chemicals induce stimulatory (i.e., “beneficial”) effects at low exposures. In many cases, nonmonotonic dose–response curves are called hormetic responses even in the absence of any mechanistic characterization of that response. Use of the term “hormesis,” with its associated descriptors, distracts from the broader and more important questions regarding the frequency and interpretation of nonmonotonic dose responses in biological systems. A better understanding of the biological basis and consequences of nonmonotonic dose–response curves is warranted for evaluating human health risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological processes. Even if certain low-dose effects were sometimes considered beneficial, this should not influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures. In this commentary we evaluate the hormesis hypothesis and potential adverse consequences of incorporating low-dose beneficial effects into public health decisions. PMID:16203233

Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis

PubMed Central

She, Guorong; Zhou, Ziqi; Zha, Zhengang; Wang, Fei; Pan, Xiaoting

2017-01-01

Subchondral bone reabsorption and remodeling are responsible for the initiation and progression of osteoarthritis (OA). Zoledronic acid (ZOL), a third-generation bisphosphonate (BIS), is an inhibitor of bone reabsorption. However, the intervention effect of ZOL on OA has not been fully characterized and remains to be directly demonstrated in animal experiments. The present study examined the microscopic and macroscopic changes in the anterior cruciate ligament transection (ACLT) model of OA in rabbits and evaluated the effects of ZOL on cartilage degeneration and subchondral bone loss. A total of 32 New Zealand white rabbits were randomly divided into four groups: High-, medium- and low-dose ZOL groups, which received an intravenous injection of 250, 50 and 10 µg/kg ZOL, respectively, after modeling, as well as an untreated group. The bone mineral density (BMD) of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative measurement of cartilage was performed by a specialized magnetic resonance imaging (MRI) technique, including three-dimensional fat-suppressed spoil gradient-recalled sequence and T2 mapping. The rabbits were sacrificed by air embolism after anesthesia and both knee joints were harvested and evaluated by general and histological observation. Toluidine blue and hematoxylin and eosin staining were used to assess histological changes in the articular cartilage. Quantitative analysis of cartilage histopathology was performed according to the Mankin scoring system. The BMD of ACLT joints dropped after modeling, which was effectively suppressed by ZOL at the high and medium dose but not the low dose. MRI scans demonstrated that in the untreated group, articular cartilages on ACLT knees were thinner than those on normal knees. The high dose of ZOL preserved the cartilage tissue thickness more efficiently than the medium and low doses. Observation of specimens and pathological slices revealed that the articular cartilage degeneration in the high-dose ZOL group was lightest, while that in the medium- and low-dose ZOL group was moderate, and the untreated group exhibited the most severe defect. The untreated group had the highest Mankin score, whereas the high-dose ZOL group had the lowest score. In conclusion, ZOL increased the subchondral bone density, improved the microstructure and reduced the degeneration of articular cartilage in OA according to morphological as well as quantitative observation. ZOL exerted significant chondroprotective effects in a dose-dependent manner. A favorable chondroprotective effect was induced at the dose of 250 µg/kg. ZOL may represent a novel promising drug to complement the treatment of OA. PMID:29201194

Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

DTIC Science & Technology

2013-05-14

enzymes . At sufficiently high doses of glutamate, this process culminates in excitogenic cell death [1]. Treatments to mitigate neuronal damage during...To evaluate the potential for therapeutic screening, we assessed the effect of several small molecule antagonists on excitotoxicity in a moderate...C. Current clamp recordings showing repeated overshooting action potentials are evoked by injection of a 75 pA current. D. Voltage-clamp recordings

What is actually measured in process evaluations for worksite health promotion programs: a systematic review

PubMed Central

2013-01-01

Background Numerous worksite health promotion program (WHPPs) have been implemented the past years to improve employees’ health and lifestyle (i.e., physical activity, nutrition, smoking, alcohol use and relaxation). Research primarily focused on the effectiveness of these WHPPs. Whereas process evaluations provide essential information necessary to improve large scale implementation across other settings. Therefore, this review aims to: (1) further our understanding of the quality of process evaluations alongside effect evaluations for WHPPs, (2) identify barriers/facilitators affecting implementation, and (3) explore the relationship between effectiveness and the implementation process. Methods Pubmed, EMBASE, PsycINFO, and Cochrane (controlled trials) were searched from 2000 to July 2012 for peer-reviewed (randomized) controlled trials published in English reporting on both the effectiveness and the implementation process of a WHPP focusing on physical activity, smoking cessation, alcohol use, healthy diet and/or relaxation at work, targeting employees aged 18-65 years. Results Of the 307 effect evaluations identified, twenty-two (7.2%) published an additional process evaluation and were included in this review. The results showed that eight of those studies based their process evaluation on a theoretical framework. The methodological quality of nine process evaluations was good. The most frequently reported process components were dose delivered and dose received. Over 50 different implementation barriers/facilitators were identified. The most frequently reported facilitator was strong management support. Lack of resources was the most frequently reported barrier. Seven studies examined the link between implementation and effectiveness. In general a positive association was found between fidelity, dose and the primary outcome of the program. Conclusions Process evaluations are not systematically performed alongside effectiveness studies for WHPPs. The quality of the process evaluations is mostly poor to average, resulting in a lack of systematically measured barriers/facilitators. The narrow focus on implementation makes it difficult to explore the relationship between effectiveness and implementation. Furthermore, the operationalisation of process components varied between studies, indicating a need for consensus about defining and operationalising process components. PMID:24341605

Evaluating health risks from occupational exposure to pesticides and the regulatory response.

PubMed Central

Woodruff, T J; Kyle, A D; Bois, F Y

1994-01-01

In this study, we used measurements of occupational exposures to pesticides in agriculture to evaluate health risks and analyzed how the federal regulatory program is addressing these risks. Dose estimates developed by the State of California from measured occupational exposures to 41 pesticides were compared to standard indices of acute toxicity (LD50) and chronic effects (reference dose). Lifetime cancer risks were estimated using cancer potencies. Estimated absorbed daily doses for mixers, loaders, and applicators of pesticides ranged from less than 0.0001% to 48% of the estimated human LD50 values, and doses for 10 of 40 pesticides exceeded 1% of the estimated human LD50 values. Estimated lifetime absorbed daily doses ranged from 0.1% to 114,000% of the reference doses developed by the U.S. Environmental Protection Agency, and doses for 13 of 25 pesticides were above them. Lifetime cancer risks ranged from 1 per million to 1700 per million, and estimates for 12 of 13 pesticides were above 1 per million. Similar results were obtained for field workers and flaggers. For the pesticides examined, exposures pose greater risks of chronic effects than acute effects. Exposure reduction measures, including use of closed mixing systems and personal protective equipment, significantly reduced exposures. Proposed regulations rely primarily on requirements for personal protective equipment and use restrictions to protect workers. Chronic health risks are not considered in setting these requirements. Reviews of pesticides by the federal pesticide regulatory program have had little effect on occupational risks. Policy strategies that offer immediate protection for workers and that are not dependent on extensive review of individual pesticides should be pursued. Images Figure 1. PMID:7713022

A geometric model for evaluating the effects of inter-fraction rectal motion during prostate radiotherapy

NASA Astrophysics Data System (ADS)

Pavel-Mititean, Luciana M.; Rowbottom, Carl G.; Hector, Charlotte L.; Partridge, Mike; Bortfeld, Thomas; Schlegel, Wolfgang

2004-06-01

A geometric model is presented which allows calculation of the dosimetric consequences of rectal motion in prostate radiotherapy. Variations in the position of the rectum are measured by repeat CT scanning during the courses of treatment of five patients. Dose distributions are calculated by applying the same conformal treatment plan to each imaged fraction and rectal dose-surface histograms produced. The 2D model allows isotropic expansion and contraction in the plane of each CT slice. By summing the dose to specific volume elements tracked by the model, composite dose distributions are produced that explicitly include measured inter-fraction motion for each patient. These are then used to estimate effective dose-surface histograms (DSHs) for the entire treatment. Results are presented showing the magnitudes of the measured target and rectal motion and showing the effects of this motion on the integral dose to the rectum. The possibility of using such information to calculate normal tissue complication probabilities (NTCP) is demonstrated and discussed.

Effective dose rate coefficients for exposure to contaminated soil

DOE PAGES

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.; ...

2017-05-10

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

Effective dose rate coefficients for exposure to contaminated soil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veinot, Kenneth G.; Eckerman, Keith F.; Bellamy, Michael B.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose ratemore » calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. As a result, the coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.« less

[Effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice].

PubMed

Xiao, Yan; Wei, Pin-Kang; Li, Jun; Shi, Jun; Yu, Zhi-Hong; Lin, Hui-Ming

2006-07-01

To evaluate the effects of Rhizoma kaempferiae volatile oil on tumor growth and cell cycle of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice. One hundred and five nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were randomly divided into seven groups: untreated group, normal saline-treated group, dissolvant-treated group, cyclophosphamide (CTX)-treated group and high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups. Corresponding interventions were implemented in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM). The ultrastructure of MKN-45 gastric cancer cells was observed by a transmission electron microscope. In the high-, medium-, and low-dose Rhizoma kaempferiae volatile oil-treated groups, the growth inhibition rates of gastric cancer were 57.2%, 28.0% and 5.0% respectively, and the gastric cancer cells were arrested at G(0)/G(1) phase. This antitumor effect was dose-dependent. The apoptotic cells occurred more frequently in the high-dose Rhizoma kaempferiae volatile oil-treated group and the CTX-treated group than those in the medium- and low-dose Rhizoma kaempferiae volatile oil-treated groups. The Rhizoma kaempferiae volatile oil is an effective composition for growth inhibition of gastric cancer, and its mechanism may be related to regulating the cell cycle and inducing apoptosis.

Synergism between tramadol and parecoxib in the orofacial formalin test.

PubMed

Isiordia-Espinoza, Mario Alberto; Zapata-Morales, Juan Ramón; Castañeda-Santana, Demian Ismael; de la Rosa-Coronado, Maximiliano; Aragon-Martinez, Othoniel Hugo

2015-05-01

The aim of this study was to evaluate the interaction between tramadol and parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min before formalin (2.5%) injection into the upper lip to characterize the dose-response curve of each individual drug in the orofacial pain test in mice. Once the dose-response curve of each drug was obtained, an experimental effective dose 50 (ED50 ) value was determined for each drug. The tramadol-parecoxib combination was evaluated in four different groups of animals. The isobolographic analysis and the interaction index were used to evaluate the nature of interaction between both drugs. The isobologram and the interaction index showed increased in the antinociceptive effect of the combination. The tramadol-parecoxib combination produces a synergism in the second phase of the orofacial formalin test. © 2015 Wiley Periodicals, Inc.

Cone beam computed tomography radiation dose and image quality assessments.

PubMed

Lofthag-Hansen, Sara

2010-01-01

Diagnostic radiology has undergone profound changes in the last 30 years. New technologies are available to the dental field, cone beam computed tomography (CBCT) as one of the most important. CBCT is a catch-all term for a technology comprising a variety of machines differing in many respects: patient positioning, volume size (FOV), radiation quality, image capturing and reconstruction, image resolution and radiation dose. When new technology is introduced one must make sure that diagnostic accuracy is better or at least as good as the one it can be expected to replace. The CBCT brand tested was two versions of Accuitomo (Morita, Japan): 3D Accuitomo with an image intensifier as detector, FOV 3 cm x 4 cm and 3D Accuitomo FPD with a flat panel detector, FOVs 4 cm x 4 cm and 6 cm x 6 cm. The 3D Accuitomo was compared with intra-oral radiography for endodontic diagnosis in 35 patients with 46 teeth analyzed, of which 41 were endodontically treated. Three observers assessed the images by consensus. The result showed that CBCT imaging was superior with a higher number of teeth diagnosed with periapical lesions (42 vs 32 teeth). When evaluating 3D Accuitomo examinations in the posterior mandible in 30 patients, visibility of marginal bone crest and mandibular canal, important anatomic structures for implant planning, was high with good observer agreement among seven observers. Radiographic techniques have to be evaluated concerning radiation dose, which requires well-defined and easy-to-use methods. Two methods: CT dose index (CTDI), prevailing method for CT units, and dose-area product (DAP) were evaluated for calculating effective dose (E) for both units. An asymmetric dose distribution was revealed when a clinical situation was simulated. Hence, the CTDI method was not applicable for these units with small FOVs. Based on DAP values from 90 patient examinations effective dose was estimated for three diagnostic tasks: implant planning in posterior mandible and examinations of impacted lower third molars and retained upper cuspids. It varied between 11-77 microSv. Radiation dose should be evaluated together with image quality. Images of a skull phantom were obtained with both units varying tube voltage, tube current, degree of rotation and FOVs. Seven observers assessed subjective image quality using a six-point rating scale for two diagnostic tasks: periapical diagnosis and implant planning in the posterior part of the jaws. Intra-observer agreement was good and inter-observer agreement moderate. Periapical diagnosis was found to, regardless of jaw, require higher exposure parameters compared to implant planning. Implant planning in the lower jaw required higher exposure parameters compared to upper jaw. Substantial dose reduction could be made without loss of diagnostic information by using a rotation of 180 degrees, in particular implant planning in upper jaw. CBCT with small FOVs was found to be well-suited for periapical diagnosis and implant planning. The CTDI method is not applicable estimating effective dose for these units. Based on DAP values effective dose varied between 11-77 microSv (ICRP 60, 1991) in a retrospectively selected patient material. Adaptation of exposure parameters to diagnostic task can give substantial dose reduction.

Estimation of the influence of radical effect in the proton beams using a combined approach with physical data and gel data

NASA Astrophysics Data System (ADS)

Haneda, K.

2016-04-01

The purpose of this study was to estimate an impact on radical effect in the proton beams using a combined approach with physical data and gel data. The study used two dosimeters: ionization chambers and polymer gel dosimeters. Polymer gel dosimeters have specific advantages when compared to other dosimeters. They can measure chemical reaction and they are at the same time a phantom that can map in three dimensions continuously and easily. First, a depth-dose curve for a 210 MeV proton beam measured using an ionization chamber and a gel dosimeter. Second, the spatial distribution of the physical dose was calculated by Monte Carlo code system PHITS: To verify of the accuracy of Monte Carlo calculation, and the calculation results were compared with experimental data of the ionization chamber. Last, to evaluate of the rate of the radical effect against the physical dose. The simulation results were compared with the measured depth-dose distribution and showed good agreement. The spatial distribution of a gel dose with threshold LET value of proton beam was calculated by the same simulation code. Then, the relative distribution of the radical effect was calculated from the physical dose and gel dose. The relative distribution of the radical effect was calculated at each depth as the quotient of relative dose obtained using physical and gel dose. The agreement between the relative distributions of the gel dosimeter and Radical effect was good at the proton beams.

Evaluation of lens absorbed dose with Cone Beam IGRT procedures.

PubMed

Palomo, R; Pujades, M C; Gimeno-Olmos, J; Carmona, V; Lliso, F; Candela-Juan, C; Vijande, J; Ballester, F; Perez-Calatayud, J

2015-12-01

The purpose of this work is to evaluate the absorbed dose to the eye lenses due to the cone beam computed tomography (CBCT) system used to accurately position the patient during head-and-neck image guided procedures. The on-board imaging (OBI) systems (v.1.5) of Clinac iX and TrueBeam (Varian) accelerators were used to evaluate the imparted dose to the eye lenses and some additional points of the head. All CBCT scans were acquired with the Standard-Dose Head protocol from Varian. Doses were measured using thermoluminescence dosimeters (TLDs) placed in an anthropomorphic phantom. TLDs were calibrated at the beam quality used to reduce their energy dependence. Average dose to the lens due to the OBI systems of the Clinac iX and the TrueBeam were 0.71  ±  0.07 mGy/CBCT and 0.70  ±  0.08 mGy/CBCT, respectively. The extra absorbed dose received by the eye lenses due to one CBCT acquisition with the studied protocol is far below the 500 mGy threshold established by ICRP for cataract formation (ICRP 2011 Statement on Tissue Reactions). However, the incremental effect of several CBCT acquisitions during the whole treatment should be taken into account.

Dosimetric Evaluation of Intensity Modulated Radiotherapy and 4-Field 3-D Conformal Radiotherapy in Prostate Cancer Treatment

PubMed Central

Uysal, Bora; Beyzadeoğlu, Murat; Sager, Ömer; Dinçoğlan, Ferrat; Demiral, Selçuk; Gamsız, Hakan; Sürenkök, Serdar; Oysul, Kaan

2013-01-01

Objective: The purpose of this dosimetric study is the targeted dose homogeneity and critical organ dose comparison of 7-field Intensity Modulated Radiotherapy (IMRT) and 3-D 4-field conformal radiotherapy. Study Design: Cross sectional study. Material and Methods: Twenty patients with low and moderate risk prostate cancer treated at Gülhane Military Medical School Radiation Oncology Department between January 2009 and December 2009 are included in this study. Two seperate dosimetric plans both for 7-field IMRT and 3D-CRT have been generated for each patient to comparatively evaluate the dosimetric status of both techniques and all the patients received 7-field IMRT. Results: Dose-comparative evaluation of two techniques revealed the superiority of IMRT technique with statistically significantly lower femoral head doses along with reduced critical organ dose-volume parameters of bladder V60 (the volume receiving 60 Gy) and rectal V40 (the volume receiving 40 Gy) and V60. Conclusion: It can be concluded that IMRT is an effective definitive management tool for prostate cancer with improved critical organ sparing and excellent dose homogenization in target organs of prostate and seminal vesicles. PMID:25207069

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

PubMed

Collery, Philippe; Santoni, François; Ciccolini, Joseph; Tran, Thi Ngoc Nga; Mohsen, Ahmed; Desmaele, Didier

2016-11-01

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD 10 ). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study.

PubMed

Kim, Soo Hyun; Jung, Seung Eun; Oh, Sang Hoon; Park, Kyu Nam; Youn, Chun Song

2011-11-03

Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies.

PubMed

Temple, Anthony R; Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K

2017-01-01

Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours.

Commercial scale irradiation for insect disinfestation preserves peach quality

NASA Astrophysics Data System (ADS)

McDonald, Heather; McCulloch, Mary; Caporaso, Fred; Winborne, Ian; Oubichon, Michon; Rakovski, Cyril; Prakash, Anuradha

2012-06-01

Irradiation is approved as a generic quarantine treatment by the US Department of Agriculture, Animal and Plant Health Inspection Service. Due to the effectiveness of irradiation in controlling insects on commodities, there is a growing need to understand the effects of low dose irradiation on fruit quality. The goal of this study was to determine the sensitivity of peaches (Prunus persica) to irradiation, and secondly, to determine the effect of commercial scale treatment on shelf-life, overall quality and consumer liking. Six varieties of peaches were irradiated in small batches at 0.29, 0.49, 0.69 and 0.90 kGy to observe the sensitivity of peaches at different dose levels. Changes in quality were evaluated by 8 trained panelists using descriptive analysis. Sensory characteristics (color, smoothness, aroma, touch firmness, mouth firmness, graininess, overall flavor and off-flavor) were evaluated at 2-4 day intervals and untreated samples served as control. To simulate commercial treatment, peaches were irradiated in pallet quantities at a target dose level of 0.4 kGy. The average absorbed dose was 0.66 kGy with an average dose uniformity ratio of 1.57. Commercially treated peaches were evaluated by 40-80 untrained consumers for acceptability routinely throughout the shelf life. Titratable acidity, Brix, texture and weight loss were also monitored for both commercial and small scale irradiated peaches. There was no dose effect on TA, Brix and weight loss due to irradiation. Peaches irradiated at 0.69 and 0.90 kGy were darker in flesh color, more juicy and less firm as determined by the trained panel and analytical pressure tests. Commercial scale irradiation did not adversely affect shelf life but was seen to enhance ripening. This, however, was perceived as a positive change by consumers. Overall, consumers rated the acceptability of irradiated peaches higher than untreated peaches. Statistical analysis was performed using linear mixed models to find determinates of irradiation on peaches.

Aflatoxin effect on erythrocyte profile and histopathology of broilers given different additives

NASA Astrophysics Data System (ADS)

Karimy, M. F.; Sutrisno, B.; Agus, A.; Suryani, A. E.; Istiqomah, L.; Damayanti, E.

2017-12-01

The aim of this study was to evaluate erythrocyte profile and microscopic changes effect of AF induces by low level (57.18 ppb) and chronic exposure (34 days) with administration of additive (Lactobacillus plantarum G7 and methionine). Aflatoxin-contaminated corn was prepared by inoculate Aspergillus flavus FNCC 6002 on corn. Total number of 576 broiler Lohman strain (MB202) unsexed DOC were allocated completely randomized into four treatments and 12 replicates, with 12 broiler chicks each. The treatments as follows: T1 = aflatoxin-contaminated diet, T2 = aflatoxin-contaminated diet + 1% of LAB (w/w), T3 = aflatoxin-contaminated diet + 0.8% of methionine (w/w), and T4 = aflatoxin-contaminated diet + 1% of LAB + 0.8% of methionine (w/w). The effect of treatments was evaluated using ANOVA and the difference among mean treatments were analyzed using DMRT. The result showed that administration of additives had no significant effect (P>0.05) on erythrocyte profile, liver, and bursa of Fabricius. The dose of additive in each treatment (T2, T3, T4) were insufficient to reduce adverse effect of chronic aflatoxicosis. It was concluded that the LAB dose for binding AF (57.18%) should be evaluated and the dose for methionine should be reduced for chronic treatment of aflatoxicosis.

Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2)

PubMed Central

Daoud, Hind M.; Soliman, Eman M.

2015-01-01

Aim: This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Materials and Methods: Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. Results: The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. Conclusion: This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis. PMID:27047027

Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2).

PubMed

Daoud, Hind M; Soliman, Eman M

2015-10-01

This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis.

Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

PubMed

Koffarnus, Mikhail N; Winger, Gail

2015-07-01

The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olson, J.J.; Friedman, R.; Orr, K.

1990-05-01

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose,more » a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.« less

Dosing of Selective Serotonin Reuptake Inhibitors Among Children and Adults Before and After the FDA Black-Box Warning.

PubMed

Bushnell, Greta A; Stürmer, Til; Swanson, Sonja A; White, Alice; Azrael, Deborah; Pate, Virginia; Miller, Matthew

2016-03-01

Prior research evaluated various effects of the 2004 black-box warning by the U.S. Food and Drug Administration (FDA) on the risk of suicidality among children associated with use of antidepressants, but the warning's effect on dosing of antidepressants has not been evaluated. This study estimated whether the initial antidepressant dose prescribed decreased and the proportion of patients who augmented the dose on the second fill increased following the 2004 warning and its 2007 expansion to young adults. The study utilized the LifeLink Health Plan Claims Database. The study cohort consisted of commercially insured children (ages 5-17), young adults (18-24), and adults (25-64) who initiated a selective serotonin reuptake inhibitor (SSRI) (citalopram, fluoxetine, paroxetine, or sertraline) from January 1, 2000, to December 31, 2009. Dose per day was determined by days' supply, strength, and quantity dispensed. Initiation with a low dose and augmentation of >1 mg/day on the second prescription before and after the 2004 warning were considered. Of 51,948 children who initiated an SSRI, 15% initiated with a low dose before the 2004 warning compared with 31% after the warning; there was a smaller change among young adults (6 percentage points) and adults (3 percentage points). The overall increase in dose augmentations among children and young adults was driven by the increase in patients initiating with a low dose. The proportion of commercially insured children initiating an SSRI with a low dose was higher after the 2004 FDA warning on the risk of suicidality among children, suggesting improved prescribing practices surrounding SSRI dosing among children.

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

PubMed

Grant, E J; Ozasa, K; Ban, N; de González, A Berrington; Cologne, J; Cullings, H M; Doi, K; Furukawa, K; Imaoka, T; Kodama, K; Nakamura, N; Niwa, O; Preston, D L; Rajaraman, P; Sadakane, A; Saigusa, S; Sakata, R; Sobue, T; Sugiyama, H; Ullrich, R; Wakeford, R; Yasumura, S; Milder, C M; Shore, R E

2015-05-01

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

Cataract production in mice by heavy charged particles

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Jose, U.; Yang, V. V.; Barker, M. E.

1981-01-01

The cataractogenic effects of heavy charged particles are evaluated in mice in relation to dose and ionization density. The relative biological effectiveness in relation to linear energy transfer for various particles is considered. Results indicated that low single doses (5 to 20 rad) of Fe 56 or Ar 40 particles are cataractogenic at 11 to 18 months after irradiation; onset and density of the opacification are dose related and cataract density (grade) at 9, 11, 13, and 16 months after irradiation shows partial linear energy transfer dependence. The severity of cataracts is reduced significantly when 417 rad of Co 60 gamma radiation is given in 24 weekly 17 rad fractions compared to giving this radiation as a single dose, but cataract severity is not reduced by fractionation of C12 doses over 24 weeks.

SU-E-I-63: Quantitative Evaluation of the Effects of Orthopedic Metal Artifact Reduction (OMAR) Software On CT Images for Radiotherapy Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jani, S

Purpose: CT simulation for patients with metal implants can often be challenging due to artifacts that obscure tumor/target delineation and normal organ definition. Our objective was to evaluate the effectiveness of Orthopedic Metal Artifact Reduction (OMAR), a commercially available software, in reducing metal-induced artifacts and its effect on computed dose during treatment planning. Methods: CT images of water surrounding metallic cylindrical rods made of aluminum, copper and iron were studied in terms of Hounsfield Units (HU) spread. Metal-induced artifacts were characterized in terms of HU/Volume Histogram (HVH) using the Pinnacle treatment planning system. Effects of OMAR on enhancing our abilitymore » to delineate organs on CT and subsequent dose computation were examined in nine (9) patients with hip implants and two (2) patients with breast tissue expanders. Results: Our study characterized water at 1000 HU with a standard deviation (SD) of about 20 HU. The HVHs allowed us to evaluate how the presence of metal changed the HU spread. For example, introducing a 2.54 cm diameter copper rod in water increased the SD in HU of the surrounding water from 20 to 209, representing an increase in artifacts. Subsequent use of OMAR brought the SD down to 78. Aluminum produced least artifacts whereas Iron showed largest amount of artifacts. In general, an increase in kVp and mA during CT scanning showed better effectiveness of OMAR in reducing artifacts. Our dose analysis showed that some isodose contours shifted by several mm with OMAR but infrequently and were nonsignificant in planning process. Computed volumes of various dose levels showed <2% change. Conclusions: In our experience, OMAR software greatly reduced the metal-induced CT artifacts for the majority of patients with implants, thereby improving our ability to delineate tumor and surrounding organs. OMAR had a clinically negligible effect on computed dose within tissues. Partially funded by unrestricted educational grant from Philips.« less

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

PubMed

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P < .0004). Psychoactive and subjective effects were dose-dependent. Measurement of neuropsychological performance proved challenging because of various disabilities in the population studied. Because the 2 active doses did not significantly differ from each other in terms of analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Dose assessment of digital tomosynthesis in pediatric imaging

NASA Astrophysics Data System (ADS)

Gislason, Amber; Elbakri, Idris A.; Reed, Martin

2009-02-01

We investigated the potential for digital tomosynthesis (DT) to reduce pediatric x-ray dose while maintaining image quality. We utilized the DT feature (VolumeRadTM) on the GE DefiniumTM 8000 flat panel system installed in the Winnipeg Children's Hospital. Facial bones, cervical spine, thoracic spine, and knee of children aged 5, 10, and 15 years were represented by acrylic phantoms for DT dose measurements. Effective dose was estimated for DT and for corresponding digital radiography (DR) and computed tomography (CT) patient image sets. Anthropomorphic phantoms of selected body parts were imaged by DR, DT, and CT. Pediatric radiologists rated visualization of selected anatomic features in these images. Dose and image quality comparisons between DR, DT, and CT determined the usefulness of tomosynthesis for pediatric imaging. CT effective dose was highest; total DR effective dose was not always lowest - depending how many projections were in the DR image set. For the cervical spine, DT dose was close to and occasionally lower than DR dose. Expert radiologists rated visibility of the central facial complex in a skull phantom as better than DR and comparable to CT. Digital tomosynthesis has a significantly lower dose than CT. This study has demonstrated DT shows promise to replace CT for some facial bones and spinal diagnoses. Other clinical applications will be evaluated in the future.

Evaluation of dosimetry and image of very low-dose computed tomography attenuation correction for pediatric positron emission tomography/computed tomography: phantom study

NASA Astrophysics Data System (ADS)

Bahn, Y. K.; Park, H. H.; Lee, C. H.; Kim, H. S.; Lyu, K. Y.; Dong, K. R.; Chung, W. K.; Cho, J. H.

2014-04-01

In this study, phantom was used to evaluate attenuation correction computed tomography (CT) dose and image in case of pediatric positron emission tomography (PET)/CT scan. Three PET/CT scanners were used along with acryl phantom in the size for infant and ion-chamber dosimeter. The CT image acquisition conditions were changed from 10 to 20, 40, 80, 100 and 160 mA and from 80 to 100, 120 and 140 kVp, which aimed at evaluating penetrate dose and computed tomography dose indexvolume (CTDIvol) value. And NEMA PET Phantom™ was used to obtain PET image under the same CT conditions in order to evaluate each attenuation-corrected PET image based on standard uptake value (SUV) value and signal-to-noise ratio (SNR). In general, the penetrate dose was reduced by around 92% under the minimum CT conditions (80 kVp and 10 mA) with the decrease in CTDIvol value by around 88%, compared with the pediatric abdomen CT conditions (100 kVp and 100 mA). The PET image with its attenuation corrected according to each CT condition showed no change in SUV value and no influence on the SNR. In conclusion, if the minimum dose CT that is properly applied to body of pediatric patient is corrected for attenuation to ensure that the effective dose is reduced by around 90% or more compared with that for adult patient, this will be useful to reduce radiation exposure level.

A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy volunteers: An open-label, parallel group, randomized clinical study.

PubMed

Chung, Hyewon; Oh, Jaeseong; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Chung, Jae-Yong

2018-01-01

The aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers. A total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration. The PK parameters after the second dose were evaluated through noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2-K, and OCT2 were genotyped, and their effects on PK characteristics were additionally evaluated. The plasma exposure of metformin increased as the metformin dose increased. The mean values for the area under the concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4 and 8808.2 h·μg/L for the low- and high-dose groups, respectively. Non-linear relationships were found between the glucose-lowering effect and PK parameters with a significant inverse trend at high metformin exposure. The PK parameters were comparable among subjects with the genetic polymorphisms. This study showed a non-linear PK-PD relationship on plasma glucose levels after the administration of metformin. The inverse relationship between systemic exposure and the glucose-lowering effect at a high exposure indicates a possible role for the intestines as an action site for metformin. ClinicalTrials.gov NCT02712619.

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

PubMed

Bagatini, Pamela Brambilla; Xavier, Léder Leal; Bertoldi, Karine; Moysés, Felipe; Lovatel, Gisele; Neves, Laura Tartari; Barbosa, Sílvia; Saur, Lisiani; de Senna, Priscylla Nunes; Souto, André Arigony; Siqueira, Ionara Rodrigues; Achaval, Matilde

2017-01-01

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs.

PubMed

Tamura, Jun; Ishizuka, Tomohito; Fukui, Sho; Oyama, Norihiko; Kawase, Kodai; Miyoshi, Kenjiro; Sano, Tadashi; Pasloske, Kirby; Yamashita, Kazuto

2015-03-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs

PubMed Central

TAMURA, Jun; ISHIZUKA, Tomohito; FUKUI, Sho; OYAMA, Norihiko; KAWASE, Kodai; MIYOSHI, Kenjiro; SANO, Tadashi; PASLOSKE, Kirby; YAMASHITA, Kazuto

2014-01-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone. PMID:25428797

A comparison of the dose from natural radionuclides and artificial radionuclides after the Fukushima nuclear accident

PubMed Central

Hosoda, Masahiro; Tokonami, Shinji; Omori, Yasutaka; Ishikawa, Tetsuo; Iwaoka, Kazuki

2016-01-01

Due to the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, the evacuees from Namie Town still cannot reside in the town, and some continue to live in temporary housing units. In this study, the radon activity concentrations were measured at temporary housing facilities, apartments and detached houses in Fukushima Prefecture in order to estimate the annual internal exposure dose of residents. A passive radon–thoron monitor (using a CR-39) and a pulse-type ionization chamber were used to evaluate the radon activity concentration. The average radon activity concentrations at temporary housing units, including a medical clinic, apartments and detached houses, were 5, 7 and 9 Bq m−3, respectively. Assuming the residents lived in these facilities for one year, the average annual effective doses due to indoor radon in each housing type were evaluated as 0.18, 0.22 and 0.29 mSv, respectively. The average effective doses to all residents in Fukushima Prefecture due to natural and artificial sources were estimated using the results of the indoor radon measurements and published data. The average effective dose due to natural sources for the evacuees from Namie Town was estimated to be 1.9 mSv. In comparison, for the first year after the FDNPP accident, the average effective dose for the evacuees due to artificial sources from the accident was 5.0 mSv. Although residents' internal and external exposures due to natural radionuclides cannot be avoided, it might be possible to lower external exposure due to the artificial radionuclides by changing some behaviors of residents. PMID:26838130

[Effectiveness of thalidomide for erythema nodosum leprosum (ENL): retrospective study of 20 Japanese cases in National Sanatrium Oku-Komyoen].

PubMed

Matsuki, Takanobu; Okano, Yoshiko; Aoki, Yoshinori; Ishida, Yutaka; Hatano, Kentaro; Kumano, Kimiko

2014-12-01

Thalidomide is a TNF-alpha inhibitor and has been administrated for erythema nodosum leprosum (ENL, Type II leprosy reaction) which is one of leprosy reactions and can cause serious illness to patients oflepromatous pole among the immune spectrum. Twenty live cases (at May, 2011) were identified to whom thalidomide had been administrated since 1978 for their ENL reactions. Data were collected from their clinical records in order to evaluate the usage and effectiveness of thalidomide in National Sanatorium Oku-Komyoen, Okayama, Setouchi-city, Japan. Individual data includes bacillary index (BI), total dose, average daily dose, maximum daily dose, minimum daily dose, methods of thalidomide administration and change of symptoms of ENL. Results: No adverse effect was found among 20 cases. Average daily dose of 20 cases was 19 mg. Regarding to the maximum daily dose, in 3 cases (15%) more than 100 mg, in 3 cases (15%) 50 mg, and in 14 cases (70%) less than 40 mg was administrated. Dose was gradually tapered in most cases. From clinical records, thalidomide was found effective for ENL in 19 cases and clinicians concerned were trying to adjust the proper dose of the drug carefully depending on the current symptoms, because there was no guideline of thalidomide administration for ENL. This data suggests that even less than 50-100 mg as the initial daily dose was still effective, though 50-100 mg daily dose is recommended in the current guideline of Japan (2011) and more dose had been administrated in USA and India.

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

Effective radiation exposure evaluation during a one year follow-up of urolithiasis patients after extracorporeal shock wave lithotripsy.

PubMed

Kaynar, Mehmet; Tekinarslan, Erdem; Keskin, Suat; Buldu, İbrahim; Sönmez, Mehmet Giray; Karatag, Tuna; Istanbulluoglu, Mustafa Okan

2015-01-01

To determine and evaluate the effective radiation exposure during a one year follow-up of urolithiasis patients following the SWL (extracorporeal shock wave lithotripsy) treatment. Total Effective Radiation Exposure (ERE) doses for each of the 129 patients: 44 kidney stone patients, 41 ureter stone patients, and 44 multiple stone location patients were calculated by adding up the radiation doses of each ionizing radiation session including images (IVU, KUB, CT) throughout a one year follow-up period following the SWL. Total mean ERE values for the kidney stone group was calculated as 15, 91 mSv (5.10-27.60), for the ureter group as 13.32 mSv (5.10-24.70), and in the multiple stone location group as 27.02 mSv (9.41-54.85). There was no statistically significant differences between the kidney and ureter groups in terms of the ERE dose values (p = 0.221) (p >0.05). In the comparison of the kidney and ureter stone groups with the multiple stone location group; however, there was a statistically significant difference (p = 0.000) (p <0.05). ERE doses should be a factor to be considered right at the initiation of any diagnostic and/or therapeutic procedure. Especially in the case of multiple stone locations, due to the high exposure to ionized radiation, different imaging modalities with low dose and/or totally without a dose should be employed in the diagnosis, treatment, and follow-up bearing the aim to optimize diagnosis while minimizing the radiation dose as much as possible.

Effects of luteinizing hormone-releasing hormone and arginine-vasotocin on the sperm-release response of Günther's Toadlet, Pseudophryne guentheri

PubMed Central

2010-01-01

Background Luteinizing hormone-releasing hormone (LHRH) is an exogenous hormone commonly used to induce spermiation in anuran amphibians. Over the past few decades, the LHRH dose administered to individuals and the frequency of injection has been highly variable. The sperm-release responses reported have been correspondingly diverse, highlighting a need to quantify dose-response relationships on a species-specific basis. This study on the Australian anuran Pseudophryne guentheri first evaluated the spermiation response of males administered one of five LHRHa doses, and second, determined whether AVT administered in combination with the optimal LHRHa dose improved sperm-release. Methods Male toadlets were administered a single dose of 0, 1, 2, 4 or 8 micrograms/g body weight of LHRHa. A 4 micrograms/g dose of AVT was administered alone or in combination with 2 micrograms/g LHRHa. Spermiation responses were evaluated at 3, 7 and 12 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Results LHRHa administration was highly effective at inducing spermiation in P. guentheri, with 100% of hormone-treated males producing sperm during the experimental period. The number of sperm released in response to 2 micrograms/g LHRHa was greater than all other doses administered and sperm viability was highest in the 1 microgram/g treatment. The administration of AVT alone or in combination with LHRHa resulted in the release of significantly lower sperm numbers. Conclusion Overall, results from this study suggest that in P. guentheri, LHRHa is effective at inducing spermiation, but that AVT inhibits sperm-release. PMID:21059269

An environmental dose experiment

NASA Astrophysics Data System (ADS)

Peralta, Luis

2017-11-01

Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained.

Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares.

PubMed

Wong, D M; Davis, J L; Alcott, C J; Hepworth-Warren, K L; Galow-Kersh, N L; Rice, S; Coetzee, J F

2015-06-01

The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted. © 2014 John Wiley & Sons Ltd.

Antinociceptive and Anti-Inflammatory Activities of Bridelia retusa Methanolic Fruit Extract in Experimental Animals

PubMed Central

Kumar, Tekeshwar; Jain, Vishal

2014-01-01

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract. PMID:25506619

Comparative analysis of dosimetry parameters for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toohey, R.E.; Stabin, M.G.

For years many have employed the concept of ``total-body dose`` or ``whole-body dose,`` i.e., the total energy deposited in the body divided by the mass of the body, when evaluating the risks of different nuclear medicine procedures. The effective dose equivalent (H{sub E}), first described in ICRP Publication 26, has been accepted by some as a better quantity to use in evaluating the total risk of a procedure, but its use has been criticized by others primarily because the tissue weighting factors were intended for use in the radiation worker, rather than the nuclear medicine patient population. Nevertheless, in ICRPmore » Publication 52, the ICRP has suggested that the H{sub E} may be used in nuclear medicine. The ICRP also has published a compendium of dose estimates, including H{sub E} values, for various nuclear medicine procedures at various ages in ICRP Publication 53. The effective dose (E) of ICRP Publication 60 is perhaps more suitable for use in nuclear medicine, with tissue weighting factors based on the entire population. Other comparisons of H{sub E} and E have been published. The authors have used the program MIRDOSE 3.1 to compute total-body dose, H{sub E}, and E for 62 radiopharmaceutical procedures, based on the best current biokinetic data available.« less

High dose gamma ray exposure effect on the properties of CdSe nanowires

NASA Astrophysics Data System (ADS)

Narula, Chetna; Chauhan, R. P.

2018-03-01

We report high dose gamma-ray (γ-ray) induced modifications incurred by polycrystalline cadmium selenide (CdSe) nanowires of 80 nm diameter. The nanowires have been synthesized using polycarbonate template assisted electro-deposition technique. The samples were irradiated with 60Co γ-radiation at a dose rate of 4.533 kGy/h for different time intervals with doses varying from 0 to 400 kGy. The effects of γ rays on the structural, morphological, optical and electrical properties of nanowires are discussed. XRD patterns of as-synthesized and gamma irradiated CdSe nanowires did not show any phase transformations but the variation in relative intensity was observed. The crystallite size evaluated using Scherrer's formula was found to vary. The optical parameters were obtained using UV-vis spectrometer measurements of absorption. Band gap was found to decrease with γ irradiation up to a dose of 300 kGy after which it was seen to increase. Refractive index and optical dielectric constants were also evaluated. Subjection of γ-radiation also brings about key changes in the electrical properties of CdSe nanowires. The attained data shows that the electrical conductivity varies with absorbed dose. The variations in the properties of CdSe nanowires can be considered as a consequence of ionization process, defect production and its annihilation.

The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs--A Review.

PubMed

Gajęcka, Magdalena; Zielonka, Łukasz; Gajęcki, Maciej

2015-11-19

The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers' interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm.

Anti-inflammatory, analgesic and antipyretic effects of Lepidagathis anobrya Nees (Acanthaceae).

PubMed

Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile

2011-01-01

This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.

A randomized, double-blind, dose-finding, multicenter, phase 2 study of radium chloride (Ra 223) in patients with bone metastases and castration-resistant prostate cancer.

PubMed

Parker, Christopher C; Pascoe, Sarah; Chodacki, Aleš; O'Sullivan, Joe M; Germá, Josep R; O'Bryan-Tear, Charles Gillies; Haider, Trond; Hoskin, Peter

2013-02-01

Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile. To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases. In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n=41), 50 kBq/kg (n=39), or 80 kBq/kg (n=42). The study compared the proportion of patients in each dose group who had a confirmed decrease of ≥ 50% in baseline prostate-specific antigen (PSA) levels. Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups. The study met its primary end point with a statistically significant dose-response relationship in confirmed ≥ 50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p=0.0297). A ≥ 50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p<0.0001). The most common treatment-related AEs (≥ 10%) occurring up to week 24 across all dose groups were diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic events was seen among dose groups. Potential limitations include small patient numbers and differences among dose groups at baseline. Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223 was well tolerated at all doses. ClinicalTrials.gov: NCT00337155. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Measuring radiation dose in computed tomography using elliptic phantom and free-in-air, and evaluating iterative metal artifact reduction algorithm

NASA Astrophysics Data System (ADS)

Morgan, Ashraf

The need for an accurate and reliable way for measuring patient dose in multi-row detector computed tomography (MDCT) has increased significantly. This research was focusing on the possibility of measuring CT dose in air to estimate Computed Tomography Dose Index (CTDI) for routine quality control purposes. New elliptic CTDI phantom that better represent human geometry was manufactured for investigating the effect of the subject shape on measured CTDI. Monte Carlo simulation was utilized in order to determine the dose distribution in comparison to the traditional cylindrical CTDI phantom. This research also investigated the effect of Siemens health care newly developed iMAR (iterative metal artifact reduction) algorithm, arthroplasty phantom was designed and manufactured that purpose. The design of new phantoms was part of the research as they mimic the human geometry more than the existing CTDI phantom. The standard CTDI phantom is a right cylinder that does not adequately represent the geometry of the majority of the patient population. Any dose reduction algorithm that is used during patient scan will not be utilized when scanning the CTDI phantom, so a better-designed phantom will allow the use of dose reduction algorithms when measuring dose, which leads to better dose estimation and/or better understanding of dose delivery. Doses from a standard CTDI phantom and the newly-designed phantoms were compared to doses measured in air. Iterative reconstruction is a promising technique in MDCT dose reduction and artifacts correction. Iterative reconstruction algorithms have been developed to address specific imaging tasks as is the case with Iterative Metal Artifact Reduction or iMAR which was developed by Siemens and is to be in use with the companys future computed tomography platform. The goal of iMAR is to reduce metal artifact when imaging patients with metal implants and recover CT number of tissues adjacent to the implant. This research evaluated iMAR capability of recovering CT numbers and reducing noise. Also, the use of iMAR should allow using lower tube voltage instead of 140 KVp which is used frequently to image patients with shoulder implants. The evaluations of image quality and dose reduction were carried out using an arthroplasty phantom.

Economic evaluation of vaccination programme of mumps vaccine to the birth cohort in Japan.

PubMed

Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

2014-07-16

The most common preventative measure against mumps is vaccination with mumps vaccine. In most parts of the world, mumps vaccine is routinely delivered through live attenuated Measles-Mumps-Rubella (MMR) vaccine. In Japan, receiving mumps vaccine is voluntary and vaccine uptake rate is less than 30%. The introduction of mumps vaccine into routine vaccination schedule has become one of the current topics in health policy and has raised the need to evaluate efficient ways in protecting children from mumps-related diseases in Japan. We conducted a cost-effectiveness analysis with Markov model and calculated incremental cost effectiveness ratios (ICERs) of 11 different programmes; a single-dose programme at 12-16 months and 10 two-dose programmes with second dose uptakes at ages 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11. Our base-case analyse set the cost per shot at ¥6951 (US$72; 1US$=96.8). Results show that single-dose programme dominates status quo. On the other hand, ICERs of all 10 two-dose programmes are under ¥6,300,000 (US$65,082) per QALY from payer's perspective while it ranged from cost-saving to <¥7,000,000 (US$72,314) per QALY from societal perspective. By adopting WHO's classification that an intervention is cost-effective if ICER (in QALY) is between one and three times of GDP as a criterion, either of the vaccination programme is concluded as cost-effective from payer's or societal perspectives. Likewise, to uptake second dose at 3-5 years old is more favourable than an uptake at any other age because of lower incremental cost-effectiveness ratios. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms.

PubMed

Moltzahn, Felix; Haeni, Katharina; Birkhäuser, Frédéric D; Roth, Beat; Thalmann, George N; Zehnder, Pascal

2013-02-01

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only. © 2012 BJU International.

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

1993-01-01

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Assessment of patient dose and radiogenic risks during endoscopic retrograde cholangiopancreatography.

PubMed

Sulieman, A; Elzaki, M; Alkhorayef, M; Babikir, E; Abuzaid, M; Dalton, A; Bradley, D

2016-11-01

Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive technique that has been used for over 30 years in the diagnosis and management of pancreaticobiliary disorders. The objectives of this study were to evaluate the patient entrance surface air kerma doses (ESAK) and estimate the organ and effective doses during ERCP in three hospitals in Khartoum. A total of 55 patients were examined in three hospitals in Khartoum state, Sudan. Calibrated thermoluinescent dosimeters (TLD) were used to measure patients' ESAK. Organ and effective doses were estimated using National Radiological Protection Board (NRPB) software. The overall mean of ESAK for all ERCP procedures was 42.4mGy. The mean patient ESAK in Fedail (A), Soba (B) and Ibn sena (C) hospitals were 26.7mGy, 26.0mGy and 72.4mGy, respectively. The effective doses in three hospitals were 1.60, 1.56 and 2.67mSv in that order and the overall mean effective dose was 1.94mSv. Patient radiation doses vary widely among the hospitals. Patient ESAK is low compared to previous studies in the light of the current practice. Patient dose was decreased significantly in the last two decades. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

PubMed

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-04-21

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

SU-G-BRC-08: Evaluation of Dose Mass Histogram as a More Representative Dose Description Method Than Dose Volume Histogram in Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, J; Eldib, A; Ma, C

2016-06-15

Purpose: Dose-volume-histogram (DVH) is widely used for plan evaluation in radiation treatment. The concept of dose-mass-histogram (DMH) is expected to provide a more representative description as it accounts for heterogeneity in tissue density. This study is intended to assess the difference between DVH and DMH for evaluating treatment planning quality. Methods: 12 lung cancer treatment plans were exported from the treatment planning system. DVHs for the planning target volume (PTV), the normal lung and other structures of interest were calculated. DMHs were calculated in a similar way as DVHs expect that the voxel density converted from the CT number wasmore » used in tallying the dose histogram bins. The equivalent uniform dose (EUD) was calculated based on voxel volume and mass, respectively. The normal tissue complication probability (NTCP) in relation to the EUD was calculated for the normal lung to provide quantitative comparison of DVHs and DMHs for evaluating the radiobiological effect. Results: Large differences were observed between DVHs and DMHs for lungs and PTVs. For PTVs with dense tumor cores, DMHs are higher than DVHs due to larger mass weighing in the high dose conformal core regions. For the normal lungs, DMHs can either be higher or lower than DVHs depending on the target location within the lung. When the target is close to the lower lung, DMHs show higher values than DVHs because the lower lung has higher density than the central portion or the upper lung. DMHs are lower than DVHs for targets in the upper lung. The calculated NTCPs showed a large range of difference between DVHs and DMHs. Conclusion: The heterogeneity of lung can be well considered using DMH for evaluating target coverage and normal lung pneumonitis. Further studies are warranted to quantify the benefits of DMH over DVH for plan quality evaluation.« less

Antinociceptive effects of nalbuphine hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; KuKanich, Butch; Keuler, Nicholas S; Klauer, Julia M; Paul-Murphy, Joanne R

2011-06-01

To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis). 14 healthy adult Hispaniolan Amazon parrots of unknown sex. 3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration. Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively. Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.

Neurogenic Effects of Low-Dose Whole-Body HZE (Fe) Ion and Gamma Irradiation

PubMed Central

Sweet, Tara B.; Hurley, Sean D.; Wu, Michael D.; Olschowka, John A.; Williams, Jacqueline P.; O’Banion, M. Kerry

2017-01-01

Understanding the dose-toxicity profile of radiation is critical when evaluating potential health risks associated with natural and man-made sources in our environment. The purpose of this study was to evaluate the effects of low-dose whole-body high-energy charged (HZE) iron (Fe) ions and low-energy gamma exposure on proliferation and differentiation of adult-born neurons within the dentate gyrus of the hippocampus, cells deemed to play a critical role in memory regulation. To determine the dose-response characteristics of the brain to whole-body Fe-ion vs. gamma-radiation exposure, C57BL/6J mice were irradiated with 1 GeV/n Fe ions or a static 137Cs source (0.662 MeV) at doses ranging from 0 to 300 cGy. The neurogenesis was analyzed at 48 h and one month postirradiation. These experiments revealed that whole-body exposure to either Fe ions or gamma radiation leads to: 1. An acute decrease in cell division within the dentate gyrus of the hippocampus, detected at doses as low as 30 and 100 cGy for Fe ions and gamma radiation, respectively; and 2. A reduction in newly differentiated neurons (DCX immunoreactivity) at one month postirradiation, with significant decreases detected at doses as low as 100 cGy for both Fe ions and gamma rays. The data presented here contribute to our understanding of brain responses to whole-body Fe ions and gamma rays and may help inform health-risk evaluations related to systemic exposure during a medical or radiologic/nuclear event or as a result of prolonged space travel. PMID:27905869

[The effect of bemetil on the production of DNA antibodies in patients with systemic lupus erythematosus].

PubMed

Lisitsyna, T A; Durnev, A D; Ivanova, M M; Speranskiĭ, A I; Seredenin, S B; Nasonova, V A

1999-01-01

The levels of autoantibodies against DNA in blood serum and severity of the disease were evaluated prior to, during, and after 8-week treatment of patients suffering from lupus erythematosus systemicus (LES) with prednisolonum (daily dose of 5-60 mg/kg, 15 patient) and with prednisolonum in combination with cyclophosphane (CP) (a total dose of 2-4 mg/kg per os. 15 patients), or bemithyl doses of 500-750 mg/day per os (15 patients) or bemithyl in combination with CP (the same doses, 16 patients). It was shown that introduction of bemithyl into LES treatment schedule significantly lowered the level of autoantibodies against DNA evaluated in immunoassay and reduced LES severity assessed using standard SLEDAI-1 and ECLAM scales.

Temporal Lobe Reactions After Radiotherapy With Carbon Ions: Incidence and Estimation of the Relative Biological Effectiveness by the Local Effect Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlampp, Ingmar; Karger, Christian P.; Jaekel, Oliver

2011-07-01

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations andmore » magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3--6.6 years). Age and maximum dose applied to at least 1 cm{sup 3} of the temporal lobe (D{sub max,V-1cm}3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm{sup 3} with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D{sub max,V-1cm}3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 {+-} 3.3 Gy equivalents (GyE) and 87.3 {+-} 2.8 GyE, respectively. Conclusions: D{sub max,V-1cm}3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM.« less

Patient-specific radiation dose and cancer risk for pediatric chest CT.

PubMed

Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

2011-06-01

To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Repeated systemic administration of the cinnamon essential oil possesses anti-anxiety and anti-depressant activities in mice.

PubMed

Sohrabi, Reyhaneh; Pazgoohan, Nasim; Seresht, Hasan Rezaei; Amin, Bahareh

2017-06-01

The present study aimed to evaluate the putative antidepressant and anti-anxiety effects of the cinnamon essential oil when administered acute (for 3 doses) and sub-acute (for 14 days) to mice. In an acute experimental study, forced swim test (FST) was conducted to evaluate the antidepressant-like behavior of animals treated with the intraperitoneal (IP) essential oil of cinnamon in triple doses (0.5, 1, and 2 mg/kg). In a sub-acute study (14 days in 24-hr intervals) antidepressant-like effects of essential oil (0.5, 1, and 2 mg/kg) with the same route were assessed in FST and tail suspension test (TST). Anti-anxiety and motor activities were evaluated using elevated plus-maze (EPM) and open field tests, respectively. Determination of different constituents within the sample oil was via gas chromatography-mass spectrometry (GC-MS) analysis. Repetitive administration of cinnamon essential oil (0.5, 1, 2 mg/kg) during 14 days significantly decreased the time of immobility in both FST and TST as compared to the control group. Mice treated with oil at the dose of 2 mg/kg spent a longer time and had more entries into the open arms of EPM as compared with the vehicle-treated ones. According to GC-MS analysis, 46 chemical compounds were identified in the studied cinnamon essential oil with the main constituent being trans-cinnamaldehyde (87.32%). Cinnamon essential oil might be used as an adjunctive therapy in improving symptoms of depressive and anxiety disorders. However, dose-response effects need further evaluation. Trans-cinnamaldehyde might be responsible for the beneficial effect observed.

Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a BCL-2 Inhibitor: Results of a Single- and Multiple-Dose Study.

PubMed

Agarwal, Suresh K; Hu, Beibei; Chien, David; Wong, Shekman L; Salem, Ahmed Hamed

2016-11-01

Venetoclax is a selective, potent, first-in-class B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in a variety of hematological malignancies. A single-dose and multiple-dose rifampin study was conducted to evaluate the effect of CYP3A induction and transporter inhibition on the pharmacokinetics of venetoclax. Subjects received a single dose of venetoclax 200 mg on day 1 of period 1 and days 1 and 14 of period 2, a single dose of rifampin 600 mg on day 1 of period 2, and rifampin 600 mg once daily on days 5 through 17 of period 2. Blood samples were collected up to 96 hours after each venetoclax dose on day 1 of period 1 and days 1 and 14 of period 2. Compared with venetoclax alone, coadministration with a single dose of rifampin increased venetoclax C max and AUC ∞ by 106% (90%CI, 73%-145%) and 78% (90%CI, 50%-111%), respectively, whereas coadministration with multiple doses of rifampin decreased venetoclax C max and AUC ∞ by 42% (90%CI, 31%-52%) and 71% (90%CI, 66%-76%), respectively. It was possible to isolate the net effect of chronic CYP3A induction from acute P-glycoprotein (P-gp) inhibition by comparing venetoclax exposures following coadministration with multiple doses of rifampin versus a single dose of rifampin, which showed that CYP3A induction decreased venetoclax C max and AUC by 72% and 84%, respectively. These results are consistent with venetoclax being a P-gp substrate and indicate that CYP3A plays a major role in venetoclax metabolism. Prescribers should consider agents with little or no CYP3A induction during treatment with venetoclax. © 2016, The American College of Clinical Pharmacology.

Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

PubMed

Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

2011-07-01

Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin bioavailability in the fed state is largely (and probably entirely) due to gastric degradation to DCA. Capsules can provide a useful and elegant dosage form for almost all drugs, but may result in a negative food effect for drugs as acid-labile as azithromycin.

Exploratory Study of 4D Versus 3D Robust Optimization in Intensity-Modulated Proton Therapy for Lung Cancer

PubMed Central

Liu, Wei; Schild, Steven E.; Chang, Joe Y.; Liao, Zhongxing; Chang, Yu-Hui; Wen, Zhifei; Shen, Jiajian; Stoker, Joshua B.; Ding, Xiaoning; Hu, Yanle; Sahoo, Narayan; Herman, Michael G.; Vargas, Carlos; Keole, Sameer; Wong, William; Bues, Martin

2015-01-01

Background To compare the impact of uncertainties and interplay effect on 3D and 4D robustly optimized intensity-modulated proton therapy (IMPT) plans for lung cancer in an exploratory methodology study. Methods IMPT plans were created for 11 non-randomly selected non-small-cell lung cancer (NSCLC) cases: 3D robustly optimized plans on average CTs with internal gross tumor volume density overridden to irradiate internal target volume, and 4D robustly optimized plans on 4D CTs to irradiate clinical target volume (CTV). Regular fractionation (66 Gy[RBE] in 33 fractions) were considered. In 4D optimization, the CTV of individual phases received non-uniform doses to achieve a uniform cumulative dose. The root-mean-square-dose volume histograms (RVH) measured the sensitivity of the dose to uncertainties, and the areas under the RVH curve (AUCs) were used to evaluate plan robustness. Dose evaluation software modeled time-dependent spot delivery to incorporate interplay effect with randomized starting phases of each field per fraction. Dose-volume histogram indices comparing CTV coverage, homogeneity, and normal tissue sparing were evaluated using Wilcoxon signed-rank test. Results 4D robust optimization plans led to smaller AUC for CTV (14.26 vs. 18.61 (p=0.001), better CTV coverage (Gy[RBE]) [D95% CTV: 60.6 vs 55.2 (p=0.001)], and better CTV homogeneity [D5%–D95% CTV: 10.3 vs 17.7 (p=0.002)] in the face of uncertainties. With interplay effect considered, 4D robust optimization produced plans with better target coverage [D95% CTV: 64.5 vs 63.8 (p=0.0068)], comparable target homogeneity, and comparable normal tissue protection. The benefits from 4D robust optimization were most obvious for the 2 typical stage III lung cancer patients. Conclusions Our exploratory methodology study showed that, compared to 3D robust optimization, 4D robust optimization produced significantly more robust and interplay-effect-resistant plans for targets with comparable dose distributions for normal tissues. A further study with a larger and more realistic patient population is warranted to generalize the conclusions. PMID:26725727

Testing equality and interval estimation in binary responses when high dose cannot be used first under a three-period crossover design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2015-01-01

When comparing two doses of a new drug with a placebo, we may consider using a crossover design subject to the condition that the high dose cannot be administered before the low dose. Under a random-effects logistic regression model, we focus our attention on dichotomous responses when the high dose cannot be used first under a three-period crossover trial. We derive asymptotic test procedures for testing equality between treatments. We further derive interval estimators to assess the magnitude of the relative treatment effects. We employ Monte Carlo simulation to evaluate the performance of these test procedures and interval estimators in a variety of situations. We use the data taken as a part of trial comparing two different doses of an analgesic with a placebo for the relief of primary dysmenorrhea to illustrate the use of the proposed test procedures and estimators.

SU-E-J-110: Dosimetric Analysis of Respiratory Motion Based On Four-Dimensional Dose Accumulation in Liver Stereotactic Body Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, S; Kim, D; Kim, T

2015-06-15

Purpose: Respiratory motion in thoracic and abdominal region could lead to significant underdosing of target and increased dose to healthy tissues. The aim of this study is to evaluate the dosimetric effect of respiratory motion in conventional 3D dose by comparing 4D deformable dose in liver stereotactic body radiotherapy (SBRT). Methods: Five patients who had previously treated liver SBRT were included in this study. Four-dimensional computed tomography (4DCT) images with 10 phases for all patients were acquired on multi-slice CT scanner (Siemens, Somatom definition). Conventional 3D planning was performed using the average intensity projection (AIP) images. 4D dose accumulation wasmore » calculated by summation of dose distribution for all phase images of 4DCT using deformable image registration (DIR) . The target volume and normal organs dose were evaluated with the 4D dose and compared with those from 3D dose. And also, Index of achievement (IOA) which assesses the consistency between planned dose and prescription dose was used to compare target dose distribution between 3D and 4D dose. Results: Although the 3D dose calculation considered the moving target coverage, significant differences of various dosimetric parameters between 4D and 3D dose were observed in normal organs and PTV. The conventional 3D dose overestimated dose to PTV, however, there was no significant difference for GTV. The average difference of IOA which become ‘1’ in an ideal case was 3.2% in PTV. The average difference of liver and duodenum was 5% and 16% respectively. Conclusion: 4D dose accumulation which can provide dosimetric effect of respiratory motion has a possibility to predict the more accurate delivered dose to target and normal organs and improve treatment accuracy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid-career Researcher Program (2014R1A2A1A10050270) through the National Research Foundation of Korea funded by the Ministry of Science, ICT&Future Planning (MSIP) of Korea.« less

The preventive effect and duration of action of two doses of inhaled furosemide on exercise-induced asthma in children.

PubMed

Novembre, E; Frongia, G; Lombardi, E; Resti, M; Zammarchi, E; Vierucci, A

1995-12-01

Exercise-induced asthma can be prevented by treatment with inhaled furosemide. In this study we evaluated the effect and duration of action of two doses (15 and 30 mg) of inhaled furosemide in prevention of exercise-induced asthma in children. Ten children with exercise-induced asthma (8 boys and 2 girls, aged 6 to 13 years) were included in the study. Each patient was tested with three treatment regimens (placebo, 15 mg of furosemide, and 30 mg of furosemide) in random order on 3 separate days. Patients performed exercise challenges on a treadmill at 20 minutes and 1, 2, 3, and 6 hours after each treatment. Pulmonary function, urinary output, and fluid intake were monitored. Both doses of furosemide had a significantly greater protective effect than placebo, but there was no significant difference between the two doses of furosemide. The higher dose of furosemide was associated with increased urinary output and had a longer duration of action. A 30 mg dose of furosemide is more effective for treatment of exercise-induced asthma in terms of duration but has a significant diuretic effect.

Patterns of Kratom use and health impact in the US-Results from an online survey.

PubMed

Grundmann, Oliver

2017-07-01

Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact. An anonymous cross-sectional online survey was conducted in October 2016 of 10,000 current Kratom users through available social media and online resources from the American Kratom Association. A total of 8049 respondents completed the survey. Kratom is primarily used by a middle-aged (31-50 years), middle-income ($35,000 and above) population for purposes of self-treating pain (68%) and emotional or mental conditions (66%). Kratom preparations present with a dose-dependent effect with negative effects, which were primarily gastrointestinal related including nausea and constipation, mainly presenting at high (5g or more/dose) and more frequent (22 or more doses/week) dosing. Kratom shows a dose-dependent opioid-like effect providing self-reported perceived beneficial effects in alleviating pain and relieving mood disorders. Kratom was primarily used for self-treatment of pain, mood disorders, and withdrawal symptoms associated with prescription opioid use. Copyright © 2017 Elsevier B.V. All rights reserved.

Different Doses of Tripterygium Glycosides in the Treatment of Diabetic Nephropathy: Effects on Blood Lipids.

PubMed

Wang, Wei

2018-06-07

The aim of this study was to investigate the therapeutic effect of different doses of tripterygium glycosides (TG) in the treatment of diabetic nephropathy (DN). The effect of TG on blood lipids and safety were also evaluated. Sixty patients with type 2 DN were randomly divided into three groups (n=20 per group): low-dose (30 mg/day TG), double-dose (60 mg/day TG) and control (placebo) groups, all three times daily for 6 months. The levels of triglycerides, total cholesterol, urinary protein, plasma albumin and serum tumour necrosis factor (TNF)-α were compared between the three groups. After treatment, urinary protein and TNF-α level significantly decreased in patients in the treatment groups, compared with the control group. This decrease was significantly larger in the double-dose group than in the low-dose group. However, there was no significant decrease in triglycerides and total cholesterol in the two treatment groups. Furthermore, plasma albumin was lower in the treatment groups than in the control group. The double dose of TG has improved clinical efficacy, compared with the low dose, and the same safety profile. © 2018 The Author(s). Published by S. Karger AG, Basel.

SU-E-T-482: In Vivo Dosimetry of An Anthropomorphic Phantom by Using the RADPOS System for Proton Beam Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohno, R; Motegi, K; Hotta, K

Purpose: Delivered doses in an anthropomorphic phantom were evaluated by using the RADPOS system for proton beam therapy. Methods: The RADPOS in vivo dosimetry system combines an electromagnetic positioning sensor with MOSFET dosimetry, allowing simultaneous online measurements of dose and spatial position. Through the RADPOS system, dose evaluation points can be determined. In vivo proton dosimetry was evaluated by using the RADPOS system and anthropomorphic head and neck phantom. MOSFET doses measured at 3D positions obtained with the RADPOS were compared to the treatment plan values that were calculated by a simplified Monte Carlo (SMC) method. Although the MOSFET responsemore » depends strongly on the linear energy transfer (LET) of proton beam, the MOSFET responses to proton beams were corrected with the SMC. Here, the SMC calculated only dose deposition determined by the experimental depth–dose distribution and lateral displacement of protons due to both multiple scattering effect in materials and incident angle. As a Result, the SMC could quickly calculate accurate doses in even heterogeneities. Results: In vivo dosimetry by using the RADPOS, as well as the MOSFET doses agreed in comparison with calculations by the SMC in the range of −3.0% to 8.3%. Most measurement errors occurred because of the uncertainties of dose calculations due to the position error of 1 mm. Conclusion: We evaluated the delivered doses in the anthropomorphic phantom by using the RADPOS system for proton beam therapy. The MOSFET doses agreed in comparison with calculations by the SMC within the measurement error. Therefore, we could successfully control the uncertainties of the measurement positions by using the RADPOS system within 1 mm in in vivo proton dosimetry. We aim for the clinical application of in vivo proton dosimetry with this RADPOS system.« less

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsui, S., E-mail: smatsui@gpi.ac.jp; Mori, Y.; Nonaka, T.

2016-05-15

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films andmore » Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.« less

Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations.

PubMed

Matsui, S; Mori, Y; Nonaka, T; Hattori, T; Kasamatsu, Y; Haraguchi, D; Watanabe, Y; Uchiyama, K; Ishikawa, M

2016-05-01

For evaluation of on-site dosimetry and process design in industrial use of ultra-low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films and Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management.

Effects of infectious virus dose and bloodmeal delivery method on susceptibility of Aedes aegypti and Aedes albopictus to chikungunya virus.

PubMed

Pesko, Kendra; Westbrook, Catherine J; Mores, Christopher N; Lounibos, L Philip; Reiskind, Michael H

2009-03-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory.

Effects of Infectious Virus Dose and Bloodmeal Delivery Method on Susceptibility of Aedes aegypti and Aedes albopictus to Chikungunya Virus

PubMed Central

Pesko, Kendra; Westbrook, Catherine J.; Mores, Christopher N.; Lounibos, L. Philip; Reiskind, Michael H.

2009-01-01

Chikungunya virus (CHIKV) is an arbovirus (genus Alphavirus, family Togaviridae) that has recently caused disease outbreaks in the Indian Ocean basin and southern Europe. These outbreaks could be associated with a possible shift in primary vector from Aedes aegypti to Ae. albopictus. To evaluate vector competence differences in possible CHIKV vectors, we evaluated the dose-dependant susceptibility of Florida strains of Ae. albopictus and Ae. aegypti for infection with a La Réunion island strain of CHIKV. Pledget and water-jacketed membrane feeding systems were also evaluated. We show that both Aedes spp. were susceptible to the highest CHIKV doses, whereas only Ae. albopictus developed disseminated infections after exposure to the two lowest doses. Infection rates for both mosquito species were significantly affected by the bloodmeal delivery method used. This information is important in assessing risk of an outbreak of imported CHIKV in the United States, in determining differences in vectorial capacity of these two vector species, and in evaluating arbovirus delivery methods in the laboratory. PMID:19351094

Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis

PubMed Central

Callera, Glaucia E.; Antunes, Tayze T.; Correa, Jose W.; Moorman, Danielle; Gutsol, Alexey; He, Ying; Cat, Aurelie Nguyen Dinh; Briones, Ana M.; Montezano, Augusto C.; Burns, Kevin D.; Touyz, Rhian M.

2016-01-01

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes. PMID:27612496

SU-E-T-409: Evaluation of Tissue Composition Effect On Dose Distribution in Radiotherapy with 6 MV Photon Beam of a Medical Linac

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghorbani, M; Tabatabaei, Z; Noghreiyan, A Vejdani

Purpose: The aim of this study is to evaluate soft tissue composition effect on dose distribution for various soft tissues and various depths in radiotherapy with 6 MV photon beam of a medical linac. Methods: A phantom and Siemens Primus linear accelerator were simulated using MCNPX Monte Carlo code. In a homogeneous cubic phantom, six types of soft tissue and three types of tissue-equivalent materials were defined separately. The soft tissues were muscle (skeletal), adipose tissue, blood (whole), breast tissue, soft tissue (9-component) and soft tissue (4-component). The tissue-equivalent materials included: water, A-150 tissue-equivalent plastic and perspex. Photon dose relativemore » to dose in 9-component soft tissue at various depths on the beam’s central axis was determined for the 6 MV photon beam. The relative dose was also calculated and compared for various MCNPX tallies including,F8, F6 and,F4. Results: The results of the relative photon dose in various materials relative to dose in 9-component soft tissue and using different tallies are reported in the form of tabulated data. Minor differences between dose distributions in various soft tissues and tissue-equivalent materials were observed. The results from F6 and F4 were practically the same but different with,F8 tally. Conclusion: Based on the calculations performed, the differences in dose distributions in various soft tissues and tissue-equivalent materials are minor but they could be corrected in radiotherapy calculations to upgrade the accuracy of the dosimetric calculations.« less

Comparison of 2 doses of recombinant human thyrotropin for thyroid function testing in healthy and suspected hypothyroid dogs.

PubMed

Boretti, F S; Sieber-Ruckstuhl, N S; Wenger-Riggenbach, B; Gerber, B; Lutz, H; Hofmann-Lehmann, R; Reusch, C E

2009-01-01

Various protocols using different doses of recombinant human thyrotropin (rhTSH) in TSH stimulation testing have been described. However, the influence of TSH dosage on thyroxine (T4) concentration has not yet been evaluated in suspected hypothyroid dogs. To evaluate the effectiveness of 2 doses of rhTSH. Fifteen dogs with clinical signs consistent with hypothyroidism and abnormal stimulation results with 75 microg rhTSH and 18 clinically healthy dogs. All dogs were stimulated with 75 and 150 microg rhTSH IV in a 1st and 2nd stimulation test, respectively. Blood samples were taken before and 6 hours after rhTSH administration for determination of total T4 concentration. Using the higher dose led to a normal test interpretation in 9 of the 15 dogs, in which stimulation had been abnormal using the lower dose. Based on follow-up information, hypothyroidism was excluded in 7 of these 9 dogs. In all 6 dogs with a blunted response to the higher dose, hypothyroidism could be confirmed. Healthy dogs showed significantly higher post-TSH T4 concentrations with the higher compared with the lower dose. Post-TSH T4 concentrations after TSH stimulation were not related to dogs' body weight in either healthy or diseased dogs. TSH dose significantly influenced test interpretation in suspected hypothyroid dogs. Differentiation between primary hypothyroidism and nonthyroidal disease was improved with 150 microg rhTSH. Because this effect was independent of the dogs' body weight, the higher dose is recommended in dogs that have concurrent disease or are receiving medication.

High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens

PubMed Central

Carter, Lawrence P.; Johnson, Matthew W.; Mintzer, Miriam Z.; Klinedinst, Margaret A.; Griffiths, Roland R.

2013-01-01

Rationale Although reports of dextromethorphan (DXM) abuse have increased recently, few studies have examined the effects of high doses of DXM. Objective This study in humans evaluated the effects of supratherapeutic doses of DXM and triazolam. Methods Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg/70kg), and placebo were administered to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Subjective, behavioral, and physiological effects were assessed repeatedly after drug administration for 6 hours. Results Triazolam produced dose-related increases in subject-rated sedation, observer-rated sedation, and behavioral impairment. DXM produced a profile of dose-related physiological and subjective effects differing from triazolam. DXM effects included increases in blood pressure, heart rate, and emesis, increases in observer-rated effects typical of classic hallucinogens (e.g. distance from reality, visual effects with eyes open and closed, joy, anxiety), and participant ratings of stimulation (e.g. jittery, nervous), somatic effects (e.g. tingling, headache), perceptual changes, end-of-session drug liking, and mystical-type experience. After 400 mg/70kg DXM, 11 of 12 participants indicated on a pharmacological class questionnaire that they thought they had received a classic hallucinogen (e.g. psilocybin). Drug effects resolved without significant adverse effects by the end of the session. In a 1-month follow up volunteers attributed increased spirituality and positive changes in attitudes, moods, and behavior to the session experiences. Conclusions High doses of DXM produced effects distinct from triazolam and had characteristics that were similar to the classic hallucinogen psilocybin. PMID:22526529

DIRECT DOSING OF PRE-WEANING RODENTS IN TOXICITY TESTING AND RESEARCH: DELIBERATIONS OF AN ILSI RSI EXPERT WORKING GROUP.

EPA Science Inventory

Laboratory animal studies that are designed to assess the effects of exposure of a test substance during postnatal development are commonly utilized in basic research and to evaluate potential hazard to children for chemical and pharmaceutical regulation. Direct dosing, defined ...

Medical and occupational dose reduction in pediatric barium meal procedures

NASA Astrophysics Data System (ADS)

Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

2017-11-01

Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

PubMed

Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

2015-01-01

Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

Feasibility Study on Applying Radiophotoluminescent Glass Dosimeters for CyberKnife SRS Dose Verification

PubMed Central

Hsu, Shih-Ming; Hung, Chao-Hsiung; Liao, Yi-Jen; Fu, Hsiao-Mei; Tsai, Jo-Ting

2017-01-01

CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%. PMID:28046056

Clinical evaluation of rosoxacin for the treatment of chancroid.

PubMed Central

Haase, D A; Ndinya-Achola, J O; Nash, R A; D'Costa, L J; Hazlett, D; Lubwama, S; Nsanze, H; Ronald, A R

1986-01-01

One hundred seven men with Haemophilus ducreyi-positive chancroid were assigned to receive 300 mg of rosoxacin as a single dose or 150 mg twice daily for 3 days. Ulcers and buboes were followed clinically and bacteriologically for 1 month. Of 40 evaluable males on the 3-day regimen, 38 (95%) were cured, while only 14 of 23 (61%) males on the single-dose regimen were cured; this regimen was discontinued. There was one ulcer relapse at day 21 in both groups; the one relapse in the single-dose group had a persistent culture-positive bubo. Eight of nine (89%) buboes followed to the endpoint on the 3-day rosoxacin regimen were cured, versus three of six (50%) on the single-dose regimen. Adverse effects were mainly related to the central nervous system but were minor and did not require intervention. None of the treatment failures was due to organisms resistant to rosoxacin, and failure of the single-dose regimen presumably was related to duration of tissue levels rather than to drug resistance. Administration of 150 mg of rosoxacin twice daily for 3 days is an effective regimen for the therapy of chancroid and is a reasonable alternative to other short-course regimens. PMID:3489439

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups.

PubMed

Limdi, Nita A; Wadelius, Mia; Cavallari, Larisa; Eriksson, Niclas; Crawford, Dana C; Lee, Ming-Ta M; Chen, Chien-Hsiun; Motsinger-Reif, Alison; Sagreiya, Hersh; Liu, Nianjun; Wu, Alan H B; Gage, Brian F; Jorgensen, Andrea; Pirmohamed, Munir; Shin, Jae-Gook; Suarez-Kurtz, Guilherme; Kimmel, Stephen E; Johnson, Julie A; Klein, Teri E; Wagner, Michael J

2010-05-06

Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compared with algorithms based solely on clinical and demographic factors. However, these algorithms better capture dose variability among whites than Asians or blacks. Herein, we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1 -1639G>A among Asians (n = 1103), blacks (n = 670), and whites (n = 3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 single nucleotide polymorphisms (SNPs) and haplotypes on warfarin dose used both univariate and multi variable linear regression. VKORC1 -1639G>A and 1173C>T individually explained the greatest variance in dose in all 3 racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among whites than blacks and Asians. Differences in the percentage of variance in dose explained by VKORC1 across race were largely accounted for by the frequency of the -1639A (or 1173T) allele. Thus, clinicians should recognize that, although at a population level, the contribution of VKORC1 toward dose requirements is higher in whites than in nonwhites; genotype predicts similar dose requirements across racial groups.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

PubMed

Son, Eun-Wha; Lee, Sung-Ryul; Choi, Hye-Sook; Koo, Hyun-Jung; Huh, Jung-Eun; Kim, Mi-Hyun; Pyo, Suhkneung

2007-06-01

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Effect of electron irradiation and bayberry polyphenols on the quality change of yellowfin tuna fillets during refrigerated storage

NASA Astrophysics Data System (ADS)

Bu, Tingting; Jin, Yang; Li, Xiaohui; Zhang, Jinjie; Xu, Dalun; Yang, Wenge; Lou, Qiaoming

2017-09-01

This study evaluated the synergistic effect of bayberry polyphenols and electron irradiation in controlling the chemical, microbiological and sensory changes of raw yellowfin tuna fillets at 4 °C for 7 days. The results indicated that the initial values of each index were dose-dependent. The dose of 5 kGy notably accelerated adenosine triphosphate degradation and lipid oxidation, while the doses of 1 and 3 kGy had acceptable sensory quality and yielded a shelf-life of 5 days. The addition of bayberry polyphenols had evident effect in inhibiting freshness breakdown, bacteria growth, histamine formation, and discoloration of tuna fillets. Bayberry polyphenols, as an antioxidant, could inhibit lipid oxidation and sensory side-effects made by irradiation up to 3 kGy. The dose of 1-3 kGy coupled with bayberry polyphenols was optimum to preserve tuna fillets which prolonged the shelf-life to 7 days.

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

PubMed

Sun, Bing; Xie, Yuan; Jiang, Jinfa; Wang, Yiping; Xu, Xiaolin; Zhao, Cuimei; Huang, Feifei

2015-04-14

Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

SU-G-BRB-17: Dosimetric Evaluation of the Respiratory Interplay Effect During VMAT Delivery Using IPAGAT Polymer Gel Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, K; Fujimoto, S; Akagi, Y

Purpose: To evaluate the dosimetric impact of the interplay effect between multileaf collimator (MLC) movement and tumor respiratory motion during delivery of volumetric modulate arc therapy (VMAT) by using customized polymer gel dosimeter. Methods: Polyacrylamide-based gel dosimeter contained magnesium chloride as a sensitizer (iPAGAT) was used in this study. An excellent gas barrier PAN (BAREX) techno bottle (φ8 cm, 650 mL) filled with iPAGAT was set to the QUASAR™ respiratory motion phantom, and was moved with motion amplitudes of 1 and 2 cm with a 4 second period during VMAT delivery by the Novalis Tx linear accelerator (Varian/BrainLAB). Two sphericalmore » tumors with a 2 cm diameter (GTV1 and GTV2) were defined, and ITV1 (GTV1+1 cm) and ITV2 (GTV2+2 cm) with expansion in the superior-inferior (S-I) direction were also defined with simulated respiratory motion. PTV margin was 2 mm around the ITV considering the setup uncertainty. Two single arc VMAT plans with 30 Gy at 3 Gy per fraction (GTV: D98>100%, PTV: D95=100%) were generated by the Varian Eclipse treatment planning system. Three-dimensional dose distribution in iPAGAT was read out by the Signa 1.5T MRI system (GE), and was evaluated by dose-volume histogram (DVH) using in-house developed software. Results: According to DVH analysis by iPAGAT, D98 of GTV1 and GTV2 were more than 100% of the prescribed dose. In contrast, D95 of PTV1 and PTV2 were about 85% and 65%, respectively. Furthermore, low-to-intermediate dose was widespread with motion amplitude of 2 cm. Conclusion: DVH analysis using iPAGAT polymer gel dosimeter was performed in this study. As a result, interplay effect was negligible, since dose coverage of GTV was sufficient during VMAT delivery with simulated respiratory motion. However, the dose reduction of PTV and the spread of low-to-intermediate dose compared to the planned dose require scrupulous attention for large tumor respiratory motion.« less

A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.

PubMed

Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A; Zwiebel, James A; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D; Ambinder, Richard F; Herman, James G; Donehower, Ross C; Carducci, Michael A

2009-10-01

This was a phase I trial to determine the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. EBV titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. The three dose regimens of 5-AC and phenylbutyrate were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient showed stable disease for 5 months whereas 26 patients showed progressive disease as the best tumor response. The administration of phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.

Evaluation of Oxalic Acid Treatments against the Mite Varroa destructor and Secondary Effects on Honey Bees Apis mellifera

PubMed Central

Adjlane, Noureddine; Tarek, El-Ounass; Haddad, Nizar

2016-01-01

Background: The Varroa destructor varroasis is a very serious parasite of honeybee Apis mellifera. The objective of this study was to evaluate the effectiveness of Varroa treatment using organic acid (oxalic acid) in Algeria identifying its side effects on bee colonies. Methods: Treatment was conducted in one apiary consisting 30 colonies kept in Langstroth hives kind. Oxalic acid dripped directly on bees 5ml of this solution of oxalic acid per lane occupied by a syringe. Three doses were tested: 4.2, 3.2 and 2.1% oxalic acid is 100, 75 and 50 g of oxalic acid dehydrate in one litter of sugar syrup (1water to1 surge) concentration. Results: The percentage of average efficiency obtained for the first dose was 81%, 72.19% for the second dose, and 65% for third one, while the dose of 100 g oxalic acid causes a weakening of honey bee colonies. Conclusion: The experiments revealed that clear variation in the treatment efficiency among colonies that this might be related to brood presence therefore in order to assure the treatment efficiency oxalic acid should be part of a bigger strategy of Varroa treatment. PMID:28032102

Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department?

PubMed

Motov, Sergey; Rosenbaum, Steven; Vilke, Gary M; Nakajima, Yuko

2016-12-01

Whether acute or chronic, emergency physicians frequently encounter patients reporting pain. It is the responsibility of the emergency physician to assess and evaluate, and if appropriate, safely and effectively reduce pain. Recently, analgesics other than opioids are being considered in an effort to provide safe alternatives for pain management in the emergency department (ED). Opioids have significant adverse effects such as respiratory depression, hypotension, and sedation, to say nothing of their potential for abuse. Although ketamine has long been used in the ED for procedural sedation and rapid sequence intubation, it is used infrequently for analgesia. Recent evidence suggests that ketamine use in subdissociative doses proves to be effective for pain control and serves as a feasible alternative to traditional opioids. This paper evaluates ketamine's analgesic effectiveness and safety in the ED. This is a literature review of randomized controlled trials, systematic reviews, meta-analyses, and observational studies evaluating ketamine for pain control in the ED setting. Based on these search parameters, eight studies were included in the final analysis and graded based on the American Academy of Emergency Medicine Clinical Practice Committee manuscript review process. A total of eight papers were reviewed in detail and graded. Recommendations were given based upon this review process. Subdissociative-dose ketamine (low-dose ketamine) is effective and safe to use alone or in combination with opioid analgesics for the treatment of acute pain in the ED. Its use is associated with higher rates of minor, but well-tolerated adverse side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-specific Radiation Dose and Cancer Risk for Pediatric Chest CT

PubMed Central

Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2011-01-01

Purpose: To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. Materials and Methods: The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0–16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDIvol) or dose–length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Results: Organ dose normalized by tube current–time product or CTDIvol decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current–time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current–time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). Conclusion: The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1 PMID:21467251

Evaluation of the Eclipse eMC algorithm for bolus electron conformal therapy using a standard verification dataset.

PubMed

Carver, Robert L; Sprunger, Conrad P; Hogstrom, Kenneth R; Popple, Richard A; Antolak, John A

2016-05-08

The purpose of this study was to evaluate the accuracy and calculation speed of electron dose distributions calculated by the Eclipse electron Monte Carlo (eMC) algorithm for use with bolus electron conformal therapy (ECT). The recent com-mercial availability of bolus ECT technology requires further validation of the eMC dose calculation algorithm. eMC-calculated electron dose distributions for bolus ECT have been compared to previously measured TLD-dose points throughout patient-based cylindrical phantoms (retromolar trigone and nose), whose axial cross sections were based on the mid-PTV (planning treatment volume) CT anatomy. The phantoms consisted of SR4 muscle substitute, SR4 bone substitute, and air. The treatment plans were imported into the Eclipse treatment planning system, and electron dose distributions calculated using 1% and < 0.2% statistical uncertainties. The accuracy of the dose calculations using moderate smoothing and no smooth-ing were evaluated. Dose differences (eMC-calculated less measured dose) were evaluated in terms of absolute dose difference, where 100% equals the given dose, as well as distance to agreement (DTA). Dose calculations were also evaluated for calculation speed. Results from the eMC for the retromolar trigone phantom using 1% statistical uncertainty without smoothing showed calculated dose at 89% (41/46) of the measured TLD-dose points was within 3% dose difference or 3 mm DTA of the measured value. The average dose difference was -0.21%, and the net standard deviation was 2.32%. Differences as large as 3.7% occurred immediately distal to the mandible bone. Results for the nose phantom, using 1% statistical uncertainty without smoothing, showed calculated dose at 93% (53/57) of the measured TLD-dose points within 3% dose difference or 3 mm DTA. The average dose difference was 1.08%, and the net standard deviation was 3.17%. Differences as large as 10% occurred lateral to the nasal air cavities. Including smoothing had insignificant effects on the accuracy of the retromolar trigone phantom calculations, but reduced the accuracy of the nose phantom calculations in the high-gradient dose areas. Dose calculation times with 1% statistical uncertainty for the retromolar trigone and nose treatment plans were 30 s and 24 s, respectively, using 16 processors (Intel Xeon E5-2690, 2.9 GHz) on a framework agent server (FAS). In comparison, the eMC was significantly more accurate than the pencil beam algorithm (PBA). The eMC has comparable accuracy to the pencil beam redefinition algorithm (PBRA) used for bolus ECT planning and has acceptably low dose calculation times. The eMC accuracy decreased when smoothing was used in high-gradient dose regions. The eMC accuracy was consistent with that previously reported for accuracy of the eMC electron dose algorithm and shows that the algorithm is suitable for clinical implementation of bolus ECT.

The use of low-dose electron-beam irradiation and storage conditions for sprout control and their effects on xanthophyllis, antioxidant capacity, and phenolics in the potato cultivar Atlantic

USDA-ARS?s Scientific Manuscript database

The effects of storage and low-dose electron-beam (e-beam) irradiation on health-promoting compounds were evaluated in the potato cultivar Atlantic. Tubers were either not exposed or subjected to 200 Gy and were either sampled immediately or stored at either 4 degrees C or ambient temperature for 10...

Radiosensitivity study and radiation effects on morphology characterization of grey oyster mushroom Pleurotus sajor-caju

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rashid, Rosnani Abdul; Awang, Mat Rasol; Mohamad, Azhar

2014-09-03

Radiosensitive dosage and morphology characterization of irradiated grey oyster mushroom Pleurotus sajor-caju by gamma rays was investigated due to effects of irradiation. In order to establish the effect, mycelium of P. sajor-caju was irradiated by gamma rays at dose 0.1 to 8.0 kGy with dose rate 0.227 Gy sec{sup −1}. The irradiation of mycelia was carried out at the radiation facility in Malaysian Nuclear Agency. The radiosensitivity study was performed by evaluating the percentage of survival irradiated mycelia. The lethal dose of the mycelium P. sajor-caju was determined at 4.0 kGy and LD{sub 50} to be equal at 2.2 kGy.more » The radiation effects on morphology were evaluated based on growth rate of irradiated mycelia, mycelia types, colonization period on substrate, morphology of fruit bodies and yields. The results shown growth rate of irradiated mycelium was slightly lower than the control and decreased as the dose increased. Irradiation was found can induced the primordia formation on PDA and the BE of irradiated seed is higher than to control. The irradiation is proven to be useful for generating new varieties of mushroom with commercial value to the industry.« less

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

NASA Technical Reports Server (NTRS)

Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

Minimizing dose variation from the interplay effect in stereotactic radiation therapy using volumetric modulated arc therapy for lung cancer.

PubMed

Kubo, Kazuki; Monzen, Hajime; Tamura, Mikoto; Hirata, Makoto; Ishii, Kentaro; Okada, Wataru; Nakahara, Ryuta; Kishimoto, Shun; Kawamorita, Ryu; Nishimura, Yasumasa

2018-03-01

It is important to improve the magnitude of dose variation that is caused by the interplay effect. The aim of this study was to investigate the impact of the number of breaths (NBs) to the dose variation for VMAT-SBRT to lung cancer. Data on respiratory motion and multileaf collimator (MLC) sequence were collected from the cases of 30 patients who underwent radiotherapy with VMAT-SBRT for lung cancer. The NBs in the total irradiation time with VMAT and the maximum craniocaudal amplitude of the target were calculated. The MLC sequence complexity was evaluated using the modulation complexity score for VMAT (MCSv). Static and dynamic measurements were performed using a cylindrical respiratory motion phantom and a micro ionization chamber. The 1 standard deviation which were obtained from 10 dynamic measurements for each patient were defined as dose variation caused by the interplay effect. The dose distributions were also verified with radiochromic film to detect undesired hot and cold dose spot. Dose measurements were also performed with different NBs in the same plan for 16 patients in 30 patients. The correlations between dose variations and parameters assessed for each treatment plan including NBs, MCSv, the MCSv/amplitude quotient (TMMCSv), and the MCSv/amplitude quotient × NBs product (IVS) were evaluated. Dose variation was decreased with increasing NBs, and NBs of >40 times maintained the dose variation within 3% in 15 cases. The correlation between dose variation and IVS which were considered NBs was shown stronger (R 2  = 0.43, P < 0.05) than TMMCSv (R 2  = 0.32, P < 0.05). The NBs is an important factor to reduce the dose variation. The patient who breathes >40 times during irradiation of two partial arcs VMAT (i.e., NBs = 16 breaths per minute) may be suitable for VMAT-SBRT for lung cancer. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21.

PubMed

He, Zhen; Paule, Merle G; Ferguson, Sherry A

2012-01-01

Perinatal treatment with relatively high doses of bisphenol A (BPA) appears to have little effect on volume of the rodent sexually dimorphic nucleus of the preoptic area (SDN-POA). However, doses more relevant to human exposures have not been examined. Here, effects of pre- and post-natal treatment with low BPA doses on SDN-POA volume of postnatal day (PND) 21 Sprague-Dawley rats were evaluated. Pregnant rats were orally gavaged with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE₂) on gestational days 6-21. Beginning on the day after birth, offspring were orally treated with the same dose their dam had received. On PND 21, offspring (n=10-15/sex/group; 1/sex/litter) were perfused and volume evaluation was conducted blind to treatment. SDN-POA outline was delineated using calbindin D28K immunoreactivity. Pairwise comparisons of the significant treatment by sex interaction indicated that neither BPA dose affected female volume. However, females treated with 5.0 or 10.0 μg/kg EE₂ exhibited volumes that were larger than same-sex controls, respectively (p<0.001). Males treated with either BPA dose or 10.0 μg/kg/day EE₂ had larger volumes than same-sex controls (p<0.006). These data indicate that BPA can have sex-specific effects on SDN-POA volume and that these effects manifest as larger volumes in males. Sensitivity of the methodology as well as the treatment paradigm was confirmed by the expected EE₂-induced increase in female volume. These treatment effects might lead to organizational changes within sexually dimorphic neuroendocrine pathways which, if persistent, could theoretically alter adult reproductive physiology and socio-sexual behavior in rats. Published by Elsevier Inc.

Retrospective Study of 122 Dogs That Were Treated with the Antifibrinolytic Drug Aminocaproic Acid: 2010-2012.

PubMed

Davis, Megan; Bracker, Kiko

2016-01-01

Antifibrinolytic drugs are used to promote hemostasis and decrease the need for red blood cell transfusion. Medical records of 122 dogs that were prescribed either oral or intravenous aminocaproic acid between 2010 and 2012 were evaluated retrospectively. Of the 122 dogs, three experienced possible drug-related adverse effects. No significant differences were identified between dogs that experienced adverse effects and those that did not and the possible adverse effects noted were all minor. All dogs that received packed red blood cell transfusions were evaluated for correlations between baseline packed cell volume or dose of red blood cells and aminocaproic acid dose and no correlation was identified. Dogs that received aminocaproic acid as a treatment for active bleeding were divided by cause of hemorrhage into the following groups: neoplastic, non-neoplastic, and unknown. No significant differences in aminocaproic acid dose or the percentage of patients requiring a blood transfusion were identified between groups.

Characterization of a developmental toxicity dose-response model.

PubMed Central

Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

1989-01-01

The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose. PMID:2707204

Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity.

PubMed

Choi, A Young; Cho, Hochan; Kim, Yu Cheol

2018-01-01

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab (IVB) injection with temporal retina-sparing laser (TRSL) photocoagulation for retinopathy of prematurity (ROP). We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-disc-diameter width temporal avascular area anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.

Evaluation and optimisation of current milrinone prescribing for the treatment and prevention of low cardiac output syndrome in paediatric patients after open heart surgery using a physiology-based pharmacokinetic drug-disease model.

PubMed

Vogt, Winnie

2014-01-01

Milrinone is the drug of choice for the treatment and prevention of low cardiac output syndrome (LCOS) in paediatric patients after open heart surgery across Europe. Discrepancies, however, among prescribing guidance, clinical studies and practice pattern require clarification to ensure safe and effective prescribing. However, the clearance prediction equations derived from classical pharmacokinetic modelling provide limited support as they have recently failed a clinical practice evaluation. Therefore, the objective of this study was to evaluate current milrinone dosing using physiology-based pharmacokinetic (PBPK) modelling and simulation to complement the existing pharmacokinetic knowledge and propose optimised dosing regimens as a basis for improving the standard of care for paediatric patients. A PBPK drug-disease model using a population approach was developed in three steps from healthy young adults to adult patients and paediatric patients with and without LCOS after open heart surgery. Pre- and postoperative organ function values from adult and paediatric patients were collected from literature and integrated into a disease model as factorial changes from the reference values in healthy adults aged 20-40 years. The disease model was combined with the PBPK drug model and evaluated against existing pharmacokinetic data. Model robustness was assessed by parametric sensitivity analysis. In the next step, virtual patient populations were created, each with 1,000 subjects reflecting the average adult and paediatric patient characteristics with regard to age, sex, bodyweight and height. They were integrated into the PBPK drug-disease model to evaluate the effectiveness of current milrinone dosing in achieving the therapeutic target range of 100-300 ng/mL milrinone in plasma. Optimised dosing regimens were subsequently developed. The pharmacokinetics of milrinone in healthy young adults as well as adult and paediatric patients were accurately described with an average fold error of 1.1 ± 0.1 (mean ± standard deviation) and mean relative deviation of 1.5 ± 0.3 as measures of bias and precision, respectively. Normalised maximum sensitivity coefficients for model input parameters ranged from -0.84 to 0.71, which indicated model robustness. The evaluation of milrinone dosing across different paediatric age groups showed a non-linear age dependence of total plasma clearance and exposure differences of a factor 1.4 between patients with and without LCOS for a fixed dosing regimen. None of the currently used dosing regimens for milrinone achieved the therapeutic target range across all paediatric age groups and adult patients, so optimised dosing regimens were developed that considered the age-dependent and pathophysiological differences. The PBPK drug-disease model for milrinone in paediatric patients with and without LCOS after open heart surgery highlights that age, disease and surgery differently impact the pharmacokinetics of milrinone, and that current milrinone dosing for LCOS is suboptimal to maintain the therapeutic target range across the entire paediatric age range. Thus, optimised dosing strategies are proposed to ensure safe and effective prescribing.

Contaminants as viral cofactors: assessing indirect population effects

USGS Publications Warehouse

Springman, Katherine R.; Kurath, Gael; Anderson, James J.; Emlen, John M.

2005-01-01

Current toxicological methods often miss contaminant effects, particularly when immune suppression is involved. The failure to recognize and evaluate indirect and sublethal effects severely limits the applicability of those methods at the population level. In this study, the Vitality model is used to evaluate the population level effects of a contaminant exerting only indirect, sublethal effects at the individual level. Juvenile rainbow trout (Oncorhynchus mykiss) were injected with 2.5 or 10.0 mg/kg doses of the model CYP1A inducer, β-naphthoflavone (BNF) as a pre-stressor, then exposed to a challenge dose of 102 or 104 pfu/fish of infectious hematopoietic necrosis virus (IHNV), an important viral pathogen of salmonids in North America. At the end of the 28-d challenge, the mortality data were processed according to the Vitality model which indicated that the correlation between the average rate of vitality loss and the pre-stressor dose was strong:R2 = 0.9944. Average time to death and cumulative mortality were dependent on the BNF dose, while no significant difference between the two viral dosages was shown, implying that the history of the organism at the time of stressor exposure is an important factor in determining the virulence or toxicity of the stressor. The conceptual framework of this model permits a smoother transfer of results to a more complex stratum, namely the population level, which allows the immunosuppressive results generated by doses of a CYP1A inducer that more accurately represent the effects elicited by environmentally-relevant contaminant concentrations to be extrapolated to target populations. The indirect effects of other environmental contaminants with similar biotransformation pathways, such as polycyclic aromatic hydrocarbons (PAH), could be assessed and quantified with this model and the results applied to a more complex biological hierarchy.

Peak skin and eye lens radiation dose from brain perfusion CT based on Monte Carlo simulation.

PubMed

Zhang, Di; Cagnon, Chris H; Villablanca, J Pablo; McCollough, Cynthia H; Cody, Dianna D; Stevens, Donna M; Zankl, Maria; Demarco, John J; Turner, Adam C; Khatonabadi, Maryam; McNitt-Gray, Michael F

2012-02-01

The purpose of our study was to accurately estimate the radiation dose to skin and the eye lens from clinical CT brain perfusion studies, investigate how well scanner output (expressed as volume CT dose index [CTDI(vol)]) matches these estimated doses, and investigate the efficacy of eye lens dose reduction techniques. Peak skin dose and eye lens dose were estimated using Monte Carlo simulation methods on a voxelized patient model and 64-MDCT scanners from four major manufacturers. A range of clinical protocols was evaluated. CTDI(vol) for each scanner was obtained from the scanner console. Dose reduction to the eye lens was evaluated for various gantry tilt angles as well as scan locations. Peak skin dose and eye lens dose ranged from 81 mGy to 348 mGy, depending on the scanner and protocol used. Peak skin dose and eye lens dose were observed to be 66-79% and 59-63%, respectively, of the CTDI(vol) values reported by the scanners. The eye lens dose was significantly reduced when the eye lenses were not directly irradiated. CTDI(vol) should not be interpreted as patient dose; this study has shown it to overestimate dose to the skin or eye lens. These results may be used to provide more accurate estimates of actual dose to ensure that protocols are operated safely below thresholds. Tilting the gantry or moving the scanning region further away from the eyes are effective for reducing lens dose in clinical practice. These actions should be considered when they are consistent with the clinical task and patient anatomy.

Forward treatment planning techniques to reduce the normalization effect in Gamma Knife radiosurgery.

PubMed

Cheng, Hao-Wen; Lo, Wei-Lun; Kuo, Chun-Yuan; Su, Yu-Kai; Tsai, Jo-Ting; Lin, Jia-Wei; Wang, Yu-Jen; Pan, David Hung-Chi

2017-11-01

In Gamma Knife forward treatment planning, normalization effect may be observed when multiple shots are used for treating large lesions. This effect can reduce the proportion of coverage of high-value isodose lines within targets. The aim of this study was to evaluate the performance of forward treatment planning techniques using the Leksell Gamma Knife for the normalization effect reduction. We adjusted the shot positions and weightings to optimize the dose distribution and reduce the overlap of high-value isodose lines from each shot, thereby mitigating the normalization effect during treatment planning. The new collimation system, Leksell Gamma Knife Perfexion, which contains eight movable sectors, provides an additional means to reduce the normalization effect by using composite shots. We propose different techniques in forward treatment planning that can reduce the normalization effect. Reducing the normalization effect increases the coverage proportion of higher isodose lines within targets, making the high-dose region within targets more uniform and increasing the mean dose to targets. Because of the increase in the mean dose to the target after reducing the normalization effect, we can set the prescribed marginal dose at a higher isodose level and reduce the maximum dose, thereby lowering the risk of complications. © 2017 Shuang Ho Hospital-Taipei Medical University. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

The contribution of interventional cardiology procedures to the population radiation dose in a ‘health-care level I’ representative region

PubMed Central

Peruzzo Cornetto, Andrea; Aimonetto, Stefania; Pisano, Francesco; Giudice, Marcello; Sicuro, Marco; Meloni, Teodoro; Tofani, Santi

2016-01-01

This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002–11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm2 were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05–0.27 mSv y−1) and the collective dose (5.8–35 man Sv y−1). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors’ institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10 % of the total dose by medical ionising radiation examination categories. PMID:26012484

Effects of amoxicillin/clavulanic acid on the pharmacokinetics of valproic acid

PubMed Central

Lee, Soo-Yun; Huh, Wooseong; Jung, Jin Ah; Yoo, Hye Min; Ko, Jae-Wook; Kim, Jung-Ryul

2015-01-01

Valproic acid (VPA) is mainly metabolized via glucuronide, which is hydrolyzed by β-glucuronidase and undergoes enterohepatic circulation. Amoxicillin/clavulanic acid (AMC) administration leads to decreased levels of β-glucuronidase-producing bacteria, suggesting that these antibiotics could interrupt enterohepatic circulation and thereby alter the pharmacokinetics of VPA. This study aimed to evaluate the effects of AMC on the pharmacokinetics of VPA. This was an open-label, two-treatment, one-sequence study in 16 healthy volunteers. Two treatments were evaluated; treatment VPA, in which a single dose of VPA 500 mg was administered, and treatment AMC + VPA, in which multiple doses of AMC 500/125 mg were administered three times daily for 7 days and then a single dose of VPA was administered. Blood samples were collected up to 48 hours. Pharmacokinetic parameters were calculated using noncompartmental methods. Fifteen subjects completed the study. Systemic exposures and peak concentrations of VPA were slightly lower with treatment AMC + VPA than with treatment VPA (AUClast, 851.0 h·mg/L vs 889.6 h·mg/L; Cmax, 52.1 mg/L vs 53.0 mg/L). There were no significant between-treatment effects on pharmacokinetics (95% confidence interval [CI]) of AUClast and Cmax (95.7 [85.9–106.5] and 98.3 [91.6–105.6], respectively). Multiple doses of AMC had no significant effects on the pharmacokinetics of VPA; thus, no dose adjustment is necessary. PMID:26309401

Radon measurements and effective dose from radon inhalation estimation in the Neapolitan catacombs.

PubMed

Quarto, M; Pugliese, M; Loffredo, F; Zambella, C; Roca, V

2014-03-01

In this study, the indoor radon activity concentrations have been measured in the Neapolitan catacombs using LR115 detectors. The detectors were exposed for two quarters, one in the warm season and the other in the cold. This has allowed one to evaluate the seasonal variations of concentrations, while the diurnal variations were evaluated performing continuous measurements by a Radim 5 monitor. The authors found that radon concentrations were lower in winter than in summer. Based on their values, taking into consideration the working hours in the catacombs and the equilibrium factor of 0.4, the effective dose to workers was estimated.

SU-E-T-145: Effects of Temporary Tachytherapy Inhibition Magnet On MOSFET Dose Measurements of Cardiovascular Implantable Electronic Devices (CIED) in Radiation Therapy Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

P, Joshi; Salomons, G; Kerr, A

2014-06-01

Purpose: To determine the effects of temporary tachytherapy inhibition magnet on MOSFET dose measurements of cardiovascular implantable electronic devices (CIED) in radiation therapy patients. Methods: Infield and peripheral MOSFET dose measurements with 6MV photon beams were performed to evaluate dose to a CIED in the presence of a doughnut shaped temporary tachytherapy inhibition magnet. Infield measurements were done to quantify the effects of the magnetic field alone and shielding by the magnet. MOSFETs were placed inside a 20×20cm{sup 2} field at a depth of 3cm in the isocentre plane in the presence and absence of the magnet. Peripheral dose measurementsmore » were done to determine the impact of the magnet on dose to the CIED in a clinical setting. These measurements were performed at the centre, under the rim and half way between a 10×10cm{sup 2} field edge and the magnet with MOSFETS placed at the surface, 0.5cm and 1cm depths in the presence and absence of the magnet. Results: Infield measurements showed that effects of magnetic field on the MOSFET readings were within the 2% MOSFET dose measurement uncertainty; a 20% attenuation of dose under the magnet rim was observed. Peripheral dose measurements at the centre of the magnet show an 8% increase in surface dose and a 6% decrease in dose at 1cm depth. Dose under the magnet rim was reduced by approximately 68%, 45% and 25% for MOSFET placed at 0.0, 0.5 and 1.0cm bolus depths, respectively. Conclusions: The magnetic field has an insignificant effect on MOSFET dose measurements. Dose to the central region of CIED represented by centre of the magnet doughnut increases at the surface, and decreases at depths due to low energy scattering contributions from the magnet. Dose under the magnet rim, representing CIED edges, decreased significantly due to shielding.« less

Oxytocin Reduces Ethanol Self-Administration in Mice

PubMed Central

King, Courtney E.; Griffin, William C.; Luderman, Lauryn N.; Kates, Malcolm M.; McGinty, Jacqueline F.; Becker, Howard C.

2017-01-01

Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder. PMID:28212464

Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2015-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:25693791

Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2014-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:24979199

The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease.

PubMed

Kim, Dong Uk; Kim, Young-Ho; Kim, Beom Jin; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul

2009-01-01

Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been widely used in patients with ulcerative colitis (UC) and Crohn's disease (CD). However, some patients cannot tolerate standard doses (2-2.5 mg/kg for AZA or 1-1.5 mg/kg for 6-MP) due to side effects such as leukopenialneutropenia. The aim of this study was to evaluate the efficacy of low dose AZA/6-MP compared to the standard dose. From 1995 to 2005, 122 patients with UC or CD treated with AZA/6-MP at Samsung Medical Center in Korea were enrolled. We divided these patients into 2 groups (standard dose group versus low dose group) according to the maintenance dose. Among the 122 patients, 17 received the standard dose and 105 received a low dose. The mean maintenance doses were 2.25 mg/kg for the standard dose group and 1.35mg/kg for the low dose group. The clinical outcomes of remission induction, maintenance of remission and relapse rate showed no significant difference in comparisons between these two groups. Low dose AZA/6-MP was as effective as the standard dose for remission induction and maintenance of remission in patients with UC and CD. For patients that develop leukopenia/neutropenia during dose escalation, maintenance therapy with low dose AZA/6-MP should be considered.

Determining organ dose conversion coefficients for external neutron irradiation by using a voxel mouse model

PubMed Central

Zhang, Xiaomin; Xie, Xiangdong; Qu, Decheng; Ning, Jing; Zhou, Hongmei; Pan, Jie; Yang, Guoshan

2016-01-01

A set of fluence-to-dose conversion coefficients has been calculated for neutrons with energies <20 MeV using a developed voxel mouse model and Monte Carlo N-particle code (MCNP), for the purpose of neutron radiation effect evaluation. The calculation used 37 monodirectional monoenergetic neutron beams in the energy range 10−9 MeV to 20 MeV, under five different source irradiation configurations: left lateral, right lateral, dorsal–ventral, ventral–dorsal, and isotropic. Neutron fluence-to-dose conversion coefficients for selected organs of the body were presented in the paper, and the effect of irradiation geometry conditions, neutron energy and the organ location on the organ dose was discussed. The results indicated that neutron dose conversion coefficients clearly show sensitivity to irradiation geometry at neutron energy below 1 MeV. PMID:26661852

EFFECTS OF IONIZING RADIATION IN CHIMPANZEES. Final Report, February 28, 1962-October 31, 1962

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riopelle, A.J.; Rogers, C.M.

1963-10-31

Results are reported from studies of the psychological, hematological, and pathological effects of a second dose of radiation to a group of chimpanzees irradiated several years before. The effects of a large dose of radiation to the head alone on previously nonirradiated animals were evaluated in 4 animals. Findings are summarized for each animal. No evidence of damage to neural tissue was seen following exposure to the head to 2000 r gamma radiation. (C.H.)

Contractile effect of the aqueous extract of Psidium guajava leaves on aortic rings in rat.

PubMed

Olatunji-Bello, I I; Odusanya, A J; Raji, I; Ladipo, C O

2007-04-01

Aqueous leaves extract of Psidium guajava significantly and dose-dependently (0.25-2 mg/ml) contracted aorta rings. The effect was evaluated also in presence of nifedipine and phentolamine. The sensitivity of the aortic rings to cumulative doses of P. guajava was significantly enhanced in the presence of phentolamine suggesting that the effect of P. guajava was to a large extent mediated by activation of alpha-adrenoceptor and to a lesser extent by acting via calcium ion channel.

Antidermatophytic activity of pyrazolo[3,4-c]isothiazoles: a preliminary approach on 4-chlorophenyl derivative for evaluation of mutagenic and clastogenic effects on bacteria and human chromosomes in vitro.

PubMed

Rossi, Damiano; Mares, Donatella; Romagnoli, Carlo; Andreotti, Elisa; Manfredini, Stefano; Vicentini, Chiara Beatrice

2011-07-01

The antifungal activity of eight pyrazolo[3,4-c]isothiazole derivatives was evaluated on five dermatophytes: three were of an anthropophilic species (i.e., Epidermophyton floccosum, Trichophyton rubrum, and Trichophyton tonsurans) and two were of a geophilic species (i.e., Microsporum gypseum and Nannizzia cajetani). The new compounds proved to be unlikely effective in inhibiting the growth of the different strains. In general, the fungi parasitic on man were more sensitive than the geophilic species. This fact can be positive for a possible practical-therapeutic utilization of this class of compounds. To verify their possible use against fungi of medical interest, the most interesting substance at low doses, 6-(4-chlorophenyl)-4-methyl-6H-pyrazolo[3,4-c]isothiazol-3-amine, was chosen to perform in vitro genotoxicity tests using the following: Salmonella/microsome test (SAL), sister chromatid excange test (SCE), cytokinesis-blocked micronucleus test (CBMN), and its improvement (Ara-C/CBMN). The compound showed no mutagenic activity at low doses, whereas at the highest dose (100 µg/mL), it caused a generalized cytotoxic effect. The high growth inhibition exerted on fungi at the lowest dose and the concomitant lack of genotoxicity, at least until the dose of 50 µg/mL, might suggest the compound as a safe candidate as an antidermatophytic substance.

The effect of systematic set-up deviations on the absorbed dose distribution for left-sided breast cancer treated with respiratory gating

NASA Astrophysics Data System (ADS)

Edvardsson, A.; Ceberg, S.

2013-06-01

The aim of this study was 1) to investigate interfraction set-up uncertainties for patients treated with respiratory gating for left-sided breast cancer, 2) to investigate the effect of the inter-fraction set-up on the absorbed dose-distribution for the target and organs at risk (OARs) and 3) optimize the set-up correction strategy. By acquiring multiple set-up images the systematic set-up deviation was evaluated. The effect of the systematic set-up deviation on the absorbed dose distribution was evaluated by 1) simulation in the treatment planning system and 2) measurements with a biplanar diode array. The set-up deviations could be decreased using a no action level correction strategy. Not using the clinically implemented adaptive maximum likelihood factor for the gating patients resulted in better set-up. When the uncorrected set-up deviations were simulated the average mean absorbed dose was increased from 1.38 to 2.21 Gy for the heart, 4.17 to 8.86 Gy to the left anterior descending coronary artery and 5.80 to 7.64 Gy to the left lung. Respiratory gating can induce systematic set-up deviations which would result in increased mean absorbed dose to the OARs if not corrected for and should therefore be corrected for by an appropriate correction strategy.

Effect of Jiangzhi tablet on gastrointestinal propulsive function in mice

NASA Astrophysics Data System (ADS)

Wang, Xiangrong; Geng, Xiuli; Zhao, Jingsheng; Fan, Lili; Zhang, Zhengchen

2018-04-01

This paper aims to study the effect of lipid-lowering tablets on gastric emptying and small intestinal propulsion in mice. Mice were randomly divided into control group, Digestant Pill group, Jiangzhi tablet group, middle dose and small dose, the mice gastric emptying phenolsulfonphthalein, gastric residual rate of phenol red indicator to evaluate the gastric emptying rate, residual rate of detection in mouse stomach; small intestine propulsion and selection of carbon ink as the experimental index. Effects were observed to promote the function of normal mice gastric emptying and intestine. The gastric emptying and small intestinal motor function of normal mice were all promoted by each administration group, and the effect was most obvious in small dose group. The effect of reducing blood lipid on gastrointestinal motility of mice ware obviously enhanced.

GDF-15 gene expression alterations in human lymphoblastoid cells and peripheral blood lymphocytes following exposure to ionizing radiation

PubMed Central

Li, Shuang; Zhang, Qing-Zhao; Zhang, De-Qin; Feng, Jiang-Bin; Luo, Qun; Lu, Xue; Wang, Xin-Ru; Li, Kun-Peng; Chen, De-Qing; Mu, Xiao-Feng; Gao, Ling; Liu, Qing-Jie

2017-01-01

The identification of rapid, sensitive and high-throughput biomarkers is imperative in order to identify individuals harmed by radiation accidents, and accurately evaluate the absorbed doses of radiation. DNA microarrays have previously been used to evaluate the alterations in growth/differentiation factor 15 (GDF15) gene expression in AHH-1 human lymphoblastoid cells, following exposure to γ-rays. The present study aimed to characterize the relationship between the dose of ionizing radiation and the produced effects in GDF-15 gene expression in AHH-1 cells and human peripheral blood lymphocytes (HPBLs). GDF-15 mRNA and protein expression levels following exposure to γ-rays and neutron radiation were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis in AHH-1 cells. In addition, alterations in GDF-15 gene expression in HPBLs following ex vivo irradiation were evaluated. The present results demonstrated that GDF-15 mRNA and protein expression levels in AHH-1 cells were significantly upregulated following exposure to γ-ray doses ranging between 1 and 10 Gy, regardless of the dose rate. A total of 48 h following exposure to neutron radiation, a dose-response relationship was identified in AHH-1 cells at γ-ray doses between 0.4 and 1.6 Gy. GDF-15 mRNA levels in HPBLs were significantly upregulated following exposure to γ-ray doses between 1 and 8 Gy, within 4–48 h following irradiation. These results suggested that significant time- and dose-dependent alterations in GDF-15 mRNA and protein expression occur in AHH-1 cells and HPBLs in the early phases following exposure to ionizing radiation. In conclusion, alterations in GDF-15 gene expression may have potential as a biomarker to evaluate radiation exposure. PMID:28440431

Effects of body habitus on internal radiation dose calculations using the 5-year-old anthropomorphic male models.

PubMed

Xie, Tianwu; Kuster, Niels; Zaidi, Habib

2017-07-13

Computational phantoms are commonly used in internal radiation dosimetry to assess the amount and distribution pattern of energy deposited in various parts of the human body from different internal radiation sources. Radiation dose assessments are commonly performed on predetermined reference computational phantoms while the argument for individualized patient-specific radiation dosimetry exists. This study aims to evaluate the influence of body habitus on internal dosimetry and to quantify the uncertainties in dose estimation correlated with the use of fixed reference models. The 5-year-old IT'IS male phantom was modified to match target anthropometric parameters, including body weight, body height and sitting height/stature ratio (SSR), determined from reference databases, thus enabling the creation of 125 5-year-old habitus-dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body morphometries. We evaluated the absorbed fractions and the mean absorbed dose to the target region per unit cumulative activity in the source region (S-values) of F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code and calculated the absorbed dose and effective dose of five 18 F-labelled radiotracers for children of various habitus. For most organs, the S-value of F-18 presents stronger statistical correlations with body weight, standing height and sitting height than BMI and SSR. The self-absorbed fraction and self-absorbed S-values of F-18 and the absorbed dose and effective dose of 18 F-labelled radiotracers present with the strongest statistical correlations with body weight. For 18 F-Amino acids, 18 F-Brain receptor substances, 18 F-FDG, 18 F-L-DOPA and 18 F-FBPA, the mean absolute effective dose differences between phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%, 13.3% and 11.4%, respectively. Total body weight, standing height and sitting height have considerable effects on human internal dosimetry. Radiation dose calculations for individual subjects using the most closely matched habitus-dependent computational phantom should be considered as an alternative to improve the accuracy of the estimates.

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.

PubMed

Vahdat, L; Wong, E T; Wile, M J; Rosenblum, M; Foley, K M; Warrell, R P

1994-11-15

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.

Effects of body habitus on internal radiation dose calculations using the 5-year-old anthropomorphic male models

NASA Astrophysics Data System (ADS)

Xie, Tianwu; Kuster, Niels; Zaidi, Habib

2017-08-01

Computational phantoms are commonly used in internal radiation dosimetry to assess the amount and distribution pattern of energy deposited in various parts of the human body from different internal radiation sources. Radiation dose assessments are commonly performed on predetermined reference computational phantoms while the argument for individualized patient-specific radiation dosimetry exists. This study aims to evaluate the influence of body habitus on internal dosimetry and to quantify the uncertainties in dose estimation correlated with the use of fixed reference models. The 5-year-old IT’IS male phantom was modified to match target anthropometric parameters, including body weight, body height and sitting height/stature ratio (SSR), determined from reference databases, thus enabling the creation of 125 5-year-old habitus-dependent male phantoms with 10th, 25th, 50th, 75th and 90th percentile body morphometries. We evaluated the absorbed fractions and the mean absorbed dose to the target region per unit cumulative activity in the source region (S-values) of F-18 in 46 source regions for the generated 125 anthropomorphic 5-year-old hybrid male phantoms using the Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code and calculated the absorbed dose and effective dose of five 18F-labelled radiotracers for children of various habitus. For most organs, the S-value of F-18 presents stronger statistical correlations with body weight, standing height and sitting height than BMI and SSR. The self-absorbed fraction and self-absorbed S-values of F-18 and the absorbed dose and effective dose of 18F-labelled radiotracers present with the strongest statistical correlations with body weight. For 18F-Amino acids, 18F-Brain receptor substances, 18F-FDG, 18F-L-DOPA and 18F-FBPA, the mean absolute effective dose differences between phantoms of different habitus and fixed reference models are 11.4%, 11.3%, 10.8%, 13.3% and 11.4%, respectively. Total body weight, standing height and sitting height have considerable effects on human internal dosimetry. Radiation dose calculations for individual subjects using the most closely matched habitus-dependent computational phantom should be considered as an alternative to improve the accuracy of the estimates.

Oral dosing in adult zebrafish: proof-of-concept using pharmacokinetics and pharmacological evaluation of carbamazepine.

PubMed

Kulkarni, Pushkar; Chaudhari, Girish Hari; Sripuram, Vijaykumar; Banote, Rakesh Kumar; Kirla, Krishna Tulasi; Sultana, Razia; Rao, Pallavi; Oruganti, Srinivas; Chatti, Kiranam

2014-02-01

We describe a method for obtaining pharmacokinetics (PK) and pharmacology data from adult zebrafish in terms of mg/kg using a novel method of oral administration. Using carbamazepine (CBZ) as a test drug, we employed dried blood spot (DBS) cards to enable drug quantification for PK; and we evaluated the pharmacological anxiolytic effect using novel tank test. The PK study confirmed the presence of CBZ in both blood and brain and the behavioural study showed dose dependent anxiolytic effect. The reproducibility of oral dosing was confirmed by the fact that the results obtained in both the experiments had negligible errors. This report enables a novel approach for optimizing the utility of zebrafish in drug discovery and drug delivery research. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effects of Irradiation Dose on Sterility Induction and Quality Parameters of Drosophila suzukii (Diptera: Drosophilidae).

PubMed

Krüger, Alexandra Peter; Schlesener, Daniele Cristine Hoffmann; Martins, Liliane Nachtigall; Wollmann, Jutiane; Deprá, Maríndia; Garcia, Flávio Roberto Mello

2018-04-02

Drosophila suzukii (Matsumura, 1931) (Diptera: Drosophilidae) is a widely distributed pest of soft-skinned and stone fruits that is controlled mainly with pesticides. An alternative to the chemical control is the sterile insect technique (SIT), an ecologically friendly method of pest management that could be used against D. suzukii. The objective of the present study was to evaluate the effects of gamma radiation on reproductive sterility, ovarian morphometry, and quality parameters of D. suzukii. Full female sterility was achieved at 75 Gy, while an adequate level of male sterility (99.67%) was obtained at 200 Gy. The ovarian size showed an exponential decay in function of irradiation dose increase. There was no significant influence of irradiation dose on the quality parameters evaluated. Our data suggest that gamma radiation can be recommended to be used in an SIT program for D. suzukii.

Evaluation of the effect of low tube voltage on radiation dose and image quality

NASA Astrophysics Data System (ADS)

Norhasrina Nik Din, Nik; Zainon, Rafidah; Rahman, A. T. Abdul

2017-05-01

Number of Computed Tomography (CT) examinations performed worldwide is increasing. In 2010, the FDA issued an initiative to reduce unnecessary radiation exposure from CT imaging. The aim of this study is to evaluate the effect of low tube voltage on radiation dose and image quality using CTDI phantom. The CTDI phantom was scanned with dual energy CT at 80 kV and 120 kV with the tube current from 150 mAs to 350 mAs. Pitch was 1.0 while slice thickness was 1 mm and 5 mm. Results show if mAs was increased, the SNR values also will be increased. The 5 mm slice thickness shows higher SNR value compared to 1 mm slice thickness. As the voltage and tube current increased, the amount of dose absorbed is also increased because current is proportional to photon flux.

Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: part I

NASA Technical Reports Server (NTRS)

Gridley, Daila S.; Pecaut, Michael J.; Dutta-Roy, Radha; Nelson, Gregory A.

2002-01-01

The goal of part I of this study was to evaluate the effects of whole-body proton irradiation on lymphoid organs and specific leukocyte populations. C57BL/6 mice were exposed to the entry region of the proton Bragg curve to total doses of 0.5 gray (Gy), 1.5 Gy, and 3.0 Gy, each delivered at a low dose rate (LDR) of 1 cGy/min and high dose rate (HDR) of 80 cGy/min. Non-irradiated and 3 Gy HDR gamma-irradiated groups were included as controls. At 4 days post-irradiation, highly significant radiation dose-dependent reductions were observed in the mass of both lymphoid organs and the numbers of leukocytes and T (CD3(+)), T helper (CD3(+)/CD4(+)), T cytotoxic (CD3(+)/CD8(+)), and B (CD19(+)) cells in both blood and spleen. A less pronounced dose effect was noted for natural killer (NK1.1(+) NK) cells in spleen. Monocyte, but not granulocyte, counts in blood were highly dose-dependent. The numbers for each population generally tended to be lower with HDR than with LDR radiation; a significant dose rate effect was found in the percentages of T and B cells, monocytes, and granulocytes and in CD4(+):CD8(+) ratios. These data indicate that mononuclear cell response to the entry region of the proton Bragg curve is highly dependent upon the total dose and that dose rate effects are evident with some cell types. Results from gamma- and proton-irradiated groups (both at 3 Gy HDR) were similar, although proton-irradiation gave consistently lower values in some measurements.

Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

PubMed

Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E; Levin, Edward D

2015-03-01

Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. Copyright © 2015 Elsevier Inc. All rights reserved.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats.

PubMed

Harris, Andrew C; Tally, Laura; Muelken, Peter; Banal, Andrew; Schmidt, Clare E; Cao, Qing; LeSage, Mark G

2015-08-01

While nicotine is the primary addictive compound in tobacco, other tobacco constituents including minor alkaloids (e.g., nornicotine, anabasine) may also contribute to tobacco addiction by mimicking or enhancing the effects of nicotine. Further evaluating the behavioral effects of minor alkaloids is essential for understanding their impact on tobacco addiction and informing development of tobacco product standards by the FDA. This study compared the addiction-related effects of nicotine and the minor alkaloids nornicotine, anabasine, myosmine, anatabine, and cotinine on intracranial self-stimulation (ICSS) thresholds in rats. Acute injection of nicotine produced reinforcement-enhancing (ICSS threshold-decreasing) effects at low to moderate doses, and reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high doses. Nornicotine and anabasine produced similar biphasic effects on ICSS thresholds, although with lower potency compared to nicotine. Myosmine only elevated ICSS thresholds at relatively high doses, while anatabine and cotinine did not influence ICSS thresholds at any dose. None of the alkaloids significantly influenced ICSS response latencies, indicating a lack of nonspecific motoric effects. These findings indicate that some minor tobacco alkaloids can either fully (nornicotine, anabasine) or partially (myosmine) mimic nicotine's addiction-related effects on ICSS, albeit at reduced potency. These findings emphasize the need for further study of the abuse potential of minor alkaloids, including evaluation of their effects when combined with nicotine and other tobacco constituents to better simulate tobacco exposure in humans. Such work is essential for informing FDA regulation of tobacco products and could also lead to the development of novel pharmacotherapies for tobacco addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Automation of PCXMC and ImPACT for NASA Astronaut Medical Imaging Dose and Risk Tracking

NASA Technical Reports Server (NTRS)

Bahadori, Amir; Picco, Charles; Flores-McLaughlin, John; Shavers, Mark; Semones, Edward

2011-01-01

To automate astronaut organ and effective dose calculations from occupational X-ray and computed tomography (CT) examinations incorporating PCXMC and ImPACT tools and to estimate the associated lifetime cancer risk per the National Council on Radiation Protection & Measurements (NCRP) using MATLAB(R). Methods: NASA follows guidance from the NCRP on its operational radiation safety program for astronauts. NCRP Report 142 recommends that astronauts be informed of the cancer risks from reported exposures to ionizing radiation from medical imaging. MATLAB(R) code was written to retrieve exam parameters for medical imaging procedures from a NASA database, calculate associated dose and risk, and return results to the database, using the Microsoft .NET Framework. This code interfaces with the PCXMC executable and emulates the ImPACT Excel spreadsheet to calculate organ doses from X-rays and CTs, respectively, eliminating the need to utilize the PCXMC graphical user interface (except for a few special cases) and the ImPACT spreadsheet. Results: Using MATLAB(R) code to interface with PCXMC and replicate ImPACT dose calculation allowed for rapid evaluation of multiple medical imaging exams. The user inputs the exam parameter data into the database and runs the code. Based on the imaging modality and input parameters, the organ doses are calculated. Output files are created for record, and organ doses, effective dose, and cancer risks associated with each exam are written to the database. Annual and post-flight exposure reports, which are used by the flight surgeon to brief the astronaut, are generated from the database. Conclusions: Automating PCXMC and ImPACT for evaluation of NASA astronaut medical imaging radiation procedures allowed for a traceable and rapid method for tracking projected cancer risks associated with over 12,000 exposures. This code will be used to evaluate future medical radiation exposures, and can easily be modified to accommodate changes to the risk calculation procedure.

Immunogenicity and Protective Efficacy in Mice and Hamsters of a β-Propiolactone Inactivated Whole Virus SARS-CoV Vaccine

PubMed Central

Roberts, Anjeanette; Lamirande, Elaine W.; Vogel, Leatrice; Baras, Benoît; Goossens, Geneviève; Knott, Isabelle; Chen, Jun; Ward, Jerrold M.; Vassilev, Ventzislav

2010-01-01

Abstract The immunogenicity and efficacy of β-propiolactone (BPL) inactivated whole virion SARS-CoV (WI-SARS) vaccine was evaluated in BALB/c mice and golden Syrian hamsters. The vaccine preparation was tested with or without adjuvants. Adjuvant Systems AS01B and AS03A were selected and tested for their capacity to elicit high humoral and cellular immune responses to WI-SARS vaccine. We evaluated the effect of vaccine dose and each adjuvant on immunogenicity and efficacy in mice, and the effect of vaccine dose with or without the AS01B adjuvant on the immunogenicity and efficacy in hamsters. Efficacy was evaluated by challenge with wild-type virus at early and late time points (4 and 18 wk post-vaccination). A single dose of vaccine with or without adjuvant was poorly immunogenic in mice; a second dose resulted in a significant boost in antibody levels, even in the absence of adjuvant. The use of adjuvants resulted in higher antibody titers, with the AS01B-adjuvanted vaccine being slightly more immunogenic than the AS03A-adjuvanted vaccine. Two doses of WI-SARS with and without Adjuvant Systems were highly efficacious in mice. In hamsters, two doses of WI-SARS with and without AS01B were immunogenic, and two doses of 2 μg of WI-SARS with and without the adjuvant provided complete protection from early challenge. Although antibody titers had declined in all groups of vaccinated hamsters 18 wk after the second dose, the vaccinated hamsters were still partially protected from wild-type virus challenge. Vaccine with adjuvant provided better protection than non-adjuvanted WI-SARS vaccine at this later time point. Enhanced disease was not observed in the lungs or liver of hamsters following SARS-CoV challenge, regardless of the level of serum neutralizing antibodies. PMID:20883165

Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.

PubMed

Chou, Ting-Chao

2006-09-01

The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

PubMed

Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

2016-08-01

Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cocaine self-administration under variable-dose schedules in squirrel monkeys.

PubMed

Panlilio, Leigh V; Thorndike, Eric B; Schindler, Charles W

2006-06-01

Squirrel monkeys self-administered cocaine under a variable-dose schedule, with the dose varied from injection to injection. As in earlier studies with rats, post-injection pauses varied as a monotonic function of dose, allowing a cocaine dose-effect curve to be obtained during each session. These curves were shifted by pretreatment with dopamine antagonists, demonstrating that this procedure may provide an efficient means of evaluating treatments that affect drug self-administration. However, drug intake eventually became "dysregulated" after extensive training (100-300 sessions), with relatively short pauses following all doses. Dose-sensitivity was restored by adding a 60-s timeout period after each injection, suggesting that dysregulation occurred because the monkeys developed a tendency to self-administer another injection before the previous injection had been adequately distributed. Finally, when the response requirement under the variable-dose schedule was increased from 1 to 10, both the post-injection pause and the rate of responding following the pause ("run rates") were found to vary with dose. The dose-dependency of run rates suggests that post-injection pauses reflect not only motivational factors, such as satiety, but also the direct effects of cocaine on leverpressing.

Effect of americium-241 alpha-particles on the dose-response of chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization.

PubMed

Barquinero, J F; Stephan, G; Schmid, E

2004-02-01

To evaluate by the fluorescent in-situ hybridization (FISH) technique the dose-response and intercellular distribution of alpha-particle-induced chromosome aberrations. In particular, the validity of using the yield of characteristic types of chromosome abnormalities in stable cells as quantitative indicators for retrospective dose reconstruction has been evaluated. Monolayers of human peripheral lymphocytes were exposed at doses from 0.02 to 1 Gy to alpha-particles emitted from a source of americium-241. The most probable energy of the alpha-particles entering the cells was 2.7 MeV. FISH painting was performed using DNA probes for chromosomes 2, 4 and 8 in combination with a pan-centromeric probe. In complete first-division cells, identified by harlequin staining, aberrations involving painted target chromosomal material were recorded as well as aberrations involving only unpainted chromosomal material. In total, the percentage of complex aberrations was about 35% and no dose dependence was observed. When complex-type exchanges were reduced to simple base types, the different cell distributions were clearly over-dispersed, and the linear coefficients of the dose-effect curves for translocations were significantly higher than for dicentrics. For past dose reconstruction, only a few complex aberrations were in stable cells. The linear coefficient obtained for transmissible aberrations in stable cells was more than seven times lower than that obtained in all analysed cells, i.e. including unstable cells. FISH-based analysis of complex rearrangements allows discrimination between partial-body exposures to low-linear energy transfer radiation and high-linear energy transfer exposures. In assessing past or chronic exposure to alpha-particles, the use of a dose-effect curve obtained by FISH-based translocation data, which had not excluded data determined in unstable cells, would underestimate the dose. Insertions are ineffective biomarkers because their frequency is too low.

SU-F-T-93: Breast Surface Dose Enhancement Using a Clinical Prone Breast Board

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guerra, M; Jozsef, G

Purpose: The use of specialized patient set-up devices in radiotherapy, such as prone breast boards, may have unwanted dosimetric effects. The goal of this study was to evaluate the effect of a clinically used prone breast board on skin dose due to buildup. Methods: GafChromic film (EBT3) was used for dose measurements on the surface of a solid water phantom shaped to mimic the curvature of the breast. We investigated two setup scenarios: the medial field border placed at the medial edge of the board and 1 cm contralaterally from that edge. A strip of film was taped to themore » medial surface of the phantom. Gantry angles varied from 10 to 30 degrees below the lateral gantry position, representing anterior oblique fields. The measurements were performed with and without the presence of the board; the ratio of their corresponding doses (dose enhancement) was evaluated. Results: For the cases where the field edge is at the edge of the board, the dose enhancement is negligible for all the tested angles. When the field edge is 1 cm inside the board, the maximum surface dose enhancement varies depending on the gantry angle between 2.2 for 30 degrees and 3.2 for 20 degrees. The length on the film at which the presence of the board is detectable (i.e. where there is dose enhancement) is longer for the shallower angles. Conclusion: Even the low-density, thin carbon fiber board with a thin soft foam pad on the top can produce significant dose enhancement on the skin in prone breast treatment due to loss of buildup. However, it happens only when the patient mid-sternum is over the board, i.e. the medial edge of the field traverses through the board and pad. Even then, the effect occurs only at the field edge, i.e. the penumbral region.« less

Practical aspects and uncertainty analysis of biological effective dose (BED) regarding its three-dimensional calculation in multiphase radiotherapy treatment plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kauweloa, Kevin I., E-mail: Kauweloa@livemail.uthscsa.edu; Gutierrez, Alonso N.; Bergamo, Angelo

2014-07-15

Purpose: There is a growing interest in the radiation oncology community to use the biological effective dose (BED) rather than the physical dose (PD) in treatment plan evaluation and optimization due to its stronger correlation with radiobiological effects. Radiotherapy patients may receive treatments involving a single only phase or multiple phases (e.g., primary and boost). Since most treatment planning systems cannot calculate the analytical BED distribution in multiphase treatments, an approximate multiphase BED expression, which is based on the total physical dose distribution, has been used. The purpose of this paper is to reveal the mathematical properties of the approximatemore » BED formulation, relative to the true BED. Methods: The mathematical properties of the approximate multiphase BED equation are analyzed and evaluated. In order to better understand the accuracy of the approximate multiphase BED equation, the true multiphase BED equation was derived and the mathematical differences between the true and approximate multiphase BED equations were determined. The magnitude of its inaccuracies under common clinical circumstances was also studied. All calculations were performed on a voxel-by-voxel basis using the three-dimensional dose matrices. Results: Results showed that the approximate multiphase BED equation is accurate only when the dose-per-fractions (DPFs) in both the first and second phases are equal, which occur when the dose distribution does not significantly change between the phases. In the case of heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the inaccuracy of the approximate multiphase BED is greater. These characteristics are usually seen in the dose distributions being delivered to organs at risk rather than to targets. Conclusions: The finding of this study indicates that the true multiphase BED equation should be implemented in the treatment planning systems due to the inconsistent accuracy of the approximate multiphase BED equation in most of the clinical situations.« less

Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.

PubMed

Nakamura, Aya; Watanabe, Masami; Sugimoto, Morito; Sako, Tomoko; Mahmood, Sabina; Kaku, Haruki; Nasu, Yasutomo; Ishii, Kazushi; Nagai, Atsushi; Kumon, Hiromi

2013-01-01

Gender identity disorder (GID) is a conflict between a person's actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendoza-Moctezuma, A. I.; Aguilar, J. Garcia; Garcia-Garduno, O. A.

Interventional cardiology procedures are an effective alternative for the reestablishment of correct sanguineous circulation in the heart. However, this kind of procedures exposes to the patients to a relatively high radiation doses. Usually, the surface peak skin dose is evaluated using a visual scale with a comparator strip, nevertheless, even if the comparator strip provides a simple and quick method for estimating the dose it has an uncertainty of {+-}25%. For this reason, a better evaluation method is needed. The objective of our project is to determine the surface peak skin dose of interventional cardiology procedures using GafChromic XR-RV2 filmmore » together with a commercial flatbed scanner in reflection mode. Here we report a protocol to handle GafChromic XR-RV2 film using a commercial flat bed scanner in reflection mode aiming at an uncertainty of {+-}3%.« less

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

PubMed Central

Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

2014-01-01

Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

Experimental and Monte Carlo evaluation of Eclipse treatment planning system for effects on dose distribution of the hip prostheses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Çatlı, Serap, E-mail: serapcatli@hotmail.com; Tanır, Güneş

2013-10-01

The present study aimed to investigate the effects of titanium, titanium alloy, and stainless steel hip prostheses on dose distribution based on the Monte Carlo simulation method, as well as the accuracy of the Eclipse treatment planning system (TPS) at 6 and 18 MV photon energies. In the present study the pencil beam convolution (PBC) method implemented in the Eclipse TPS was compared to the Monte Carlo method and ionization chamber measurements. The present findings show that if high-Z material is used in prosthesis, large dose changes can occur due to scattering. The variance in dose observed in the presentmore » study was dependent on material type, density, and atomic number, as well as photon energy; as photon energy increased back scattering decreased. The dose perturbation effect of hip prostheses was significant and could not be predicted accurately by the PBC method for hip prostheses. The findings show that for accurate dose calculation the Monte Carlo-based TPS should be used in patients with hip prostheses.« less

Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

PubMed

Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

2013-05-20

Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

PubMed

Clarke, D O; Hilbish, K G; Waters, D G; Newcomb, D L; Chellman, G J

2015-12-01

The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiotherapy in the management of keloids. Clinical experience with electron beam irradiation and comparison with X-ray therapy.

PubMed

Maarouf, Mohammad; Schleicher, Ursula; Schmachtenberg, Axel; Ammon, Jürgen

2002-06-01

Aim of this study was to evaluate the advantages of electron beam irradiation compared to kilovoltage X-ray therapy in the treatment of keloids. Furthermore, the risk of developing malignancy following keloid radiotherapy was assessed. An automatic water phantom was used to evaluate the dose distribution in tissue. Furthermore, a series of measurements was done on the patients using thermoluminescence dosimeters (TLD) to estimate the doses absorbed by the organs at risk. We also report our clinical experience with electron beam radiation of 134 keloids following surgical excision. Electron beam irradiation offers a high control rate (84%) with minimal side effects for keloids. Electron irradiation provides better dose distribution in tissue, and therefore less radiation burden to the organs at risk. After a mean follow-up period of 7.2 years, no severe side effects or malignancies were observed after keloid radiotherapy. Electron radiation therapy is superior to kilovoltage irradiation for treating keloids due to better dose distribution in tissue. In agreement with the literature, no cases of malignancy were observed after keloid irradiation.

In vivo safety evaluation of UP780, a standardized composition of aloe chromone aloesin formulated with an Aloe vera inner leaf fillet.

PubMed

Yimam, Mesfin; Brownell, Lidia; Jia, Qi

2014-08-01

Safety profiles of the aloe chromone aloesin or Aloe vera inner leaf fillet (Qmatrix) as a well tolerated entity have been reported separately. UP780, a standardized composition of aloe chromone formulated with an Aloe vera inner leaf fillet, has shown a significant beneficial effect in lowering blood glucose and improving insulin resistance in human. Here we evaluate the safety of UP780 after a repeated 14 and 90-day oral administration in CD-1 mice. UP780 was given at doses of 100mg/kg/day, 500mg/kg/day and 1000mg/kg/day to groups of 10 male and 10 female for 90days or administered by oral gavage at a dose of 2g/kg/day to groups of 5 male and 5 female for 14days. Body weight, feed consumption, hematology, clinical chemistry and histopathologic evaluation were performed. UP780 at a dose of 1000mg/kg/day or at 2000mg/kg/day produced no treatment-related toxicity or mortality. Body weight gain or feed consumption was similar between groups. There was no test article-related microscopic change. Spontaneously occurring minor changes in clinical chemistry and hematology were observed. However, these changes were limited to one sex or were not dose correlated. UP780 was well tolerated in this strain. A dose of 2000mg/kg/day was identified as the NOAEL (no-observed-adverse-effect-level). Copyright © 2014 Elsevier Inc. All rights reserved.

Physical and radiological properties of radiochromic gel as of its composition

NASA Astrophysics Data System (ADS)

Lee, Sang Hoon; Kim, Juree; Shim, Su Jung; Chang, Kyung Hwan; Lim, Sangwook; Huh, Hyun Do; Shin, Dong Oh; Cho, Sam Ju

2014-04-01

In the research, we evaluated the use of leuco crystal violet (LCV) gel as a dosimeter for therapeutic radiation by investigating its optical characteristics at various component concentrations. We also investigated the aging effect of the LCV gel at different beam energies, doserates, and dosing times to evaluate the LCV's applicability to radiation therapy. We confirmed that the optimal optical wavelength of the LCV gel dosimeter was 600 nm. The dose sensitivity increased with increasing concentration of LCV; however, the optimal concentration was 1 mM LCV because the transparency of the gel dosimeter is important for use in optical CT scanners. However, the dose sensitivity decreased with increasing concentration of trichloroacetic acid (TAA). Moreover, the transparency of LCV rapidly decreased because of the generation of a white precipitate at TAA concentrations below 25 mM. Thus, an optimal TAA concentration of 30 mM was used in this study. Triton X-100 (8 mM) was identified as the optimal reagent for determining the optimum gel transparency and dose sensitivity. Thus, we present an LCV gel dosimeter composed of 4% gelatin by mass, 1 mM LCV, 30 mM TAA, and 8-mM Triton X-100 for use with an optical CT scanner. We showed good dose linearity up to 30 Gy. There was a little doserate dependency at a beam energy of 6 MV while the doserate dependence was more than 4.2% at a beam energy of 10 MV. To evaluate the energy dependence of the LCV gel dosimeter, we irradiated it at 20 Gy by using 6 MV and 10 MV beams. At the high doserate, the difference in the dose energy dependence was relatively small at approximately 1%, but the difference increased to 4.6% at the low doserate. With respect to the radiation absorbance at a photon energy of 6 MV, the absorbance at an electron energy of 6 MeV decreased by 5.4%, and the absorbances at 9, 12, and 15 MeV increased by 3, 18.7, and 12.2%, respectively. Furthermore, the aging effect was larger in the low-dose group then in the high-dose group. Moreover, we observed that the absorbance between 24 and 48 h after irradiation increased by approximately 5% at 5 Gy. For gel groups tested at high doses, the aging effect was reduced by approximately 1%.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arbique, G; Anderson, J; Guild, J

Purpose: The National Lung Screening Trial mandated manual low dose CT technique factors, where up to a doubling of radiation output could be used over a regular to large patient size range. Recent guidance from the AAPM and ACR for lung cancer CT screening recommends radiation output adjustment for patient size either through AEC or a manual technique chart. This study evaluated the use of AEC for output control and dose reduction. Methods: The study was performed on a multidetector helical CT scanner (Aquillion ONE, Toshiba Medical) equipped with iterative reconstruction (ADIR-3D), AEC was adjusted with a standard deviation (SD)more » image quality noise index. The protocol SD parameter was incrementally increased to reduce patient population dose while image quality was evaluated by radiologist readers scoring the clinical utility of images on a Likert scale. Results: Plots of effective dose vs. body size (water cylinder diameter reported by the scanner) demonstrate monotonic increase in patient dose with increasing patient size. At the initial SD setting of 19 the average CTDIvol for a standard size patient was ∼ 2.0 mGy (1.2 mSv effective dose). This was reduced to ∼1.0 mGy (0.5 mSv) at an SD of 25 with no noticeable reduction in clinical utility of images as demonstrated by Likert scoring. Plots of effective patient diameter and BMI vs body size indicate that these metrics could also be used for manual technique charts. Conclusion: AEC offered consistent and reliable control of radiation output in this study. Dose for a standard size patient was reduced to one-third of the 3 mGy CTDIvol limit required for ACR accreditation of lung cancer CT screening. Gary Arbique: Research Grant, Toshiba America Medical Systems; Cecelia Brewington: Research Grant, Toshiba America Medical Systems; Di Zhang: Employee, Toshiba America Medical Systems.« less

Effective radiation exposure evaluation during a one year follow-up of urolithiasis patients after extracorporeal shock wave lithotripsy

PubMed Central

Tekinarslan, Erdem; Keskin, Suat; Buldu, İbrahim; Sönmez, Mehmet Giray; Karatag, Tuna; Istanbulluoglu, Mustafa Okan

2015-01-01

Introduction To determine and evaluate the effective radiation exposure during a one year follow-up of urolithiasis patients following the SWL (extracorporeal shock wave lithotripsy) treatment. Material and methods Total Effective Radiation Exposure (ERE) doses for each of the 129 patients: 44 kidney stone patients, 41 ureter stone patients, and 44 multiple stone location patients were calculated by adding up the radiation doses of each ionizing radiation session including images (IVU, KUB, CT) throughout a one year follow-up period following the SWL. Results Total mean ERE values for the kidney stone group was calculated as 15, 91 mSv (5.10-27.60), for the ureter group as 13.32 mSv (5.10-24.70), and in the multiple stone location group as 27.02 mSv (9.41-54.85). There was no statistically significant differences between the kidney and ureter groups in terms of the ERE dose values (p = 0.221) (p >0.05). In the comparison of the kidney and ureter stone groups with the multiple stone location group; however, there was a statistically significant difference (p = 0.000) (p <0.05). Conclusions ERE doses should be a factor to be considered right at the initiation of any diagnostic and/or therapeutic procedure. Especially in the case of multiple stone locations, due to the high exposure to ionized radiation, different imaging modalities with low dose and/or totally without a dose should be employed in the diagnosis, treatment, and follow-up bearing the aim to optimize diagnosis while minimizing the radiation dose as much as possible. PMID:26568880

Evaluation of Cameroonian plants towards experimental bone regeneration.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

2012-05-07

Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control. Ethanolic extracts of EM and SA accelerate fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying their traditional use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Evaluation of botulinum toxin type A effectiveness in preventing postoperative intraperitoneal adhesions

PubMed Central

Uysal, Erdal

2017-01-01

Purpose Postoperative intraperitoneal adhesions (PIAs) are one of the most important problems surgeons have to face after laparotomies. In this study, we aimed to evaluate the effectiveness of local application of botulinum toxin type A (BoNT-A) in various dosages on the prevention of intra-abdominal adhesions in rats with experimental intra-abdominal adhesions. Methods Forty Wistar Albino female rats were randomly separated into 4 groups. The 4 groups were determined as follows: Control (group 1, n = 10); Sham (group 2, n = 10); 10-µg/kg low-dose BoNT-A (group 3, n = 10) and 30-µg/kg high-dose BoNT-A (group 4, n = 10). Subserosal injuries were created on the caecum of all rats. Laparotomy was performed on the fifth day. Adhesion scores, histopathological examination, and E-cadherin expression levels were evaluated. Results General adhesion scores for groups 1 and 2 were determined to be significantly high when compared to group 4 (P < 0.001). A significant difference was also determined between groups 3 and 4 in terms of general adhesion scores (P < 0.05). In pair comparisons, a significant decrease in high-dose BoNT-A group (group 4) when compared to groups 1 and 2 in terms of neovascularization, fibroblast density, collagen deposition and inflammatory cell count was determined (P < 0.05). Conclusion A significant decrease was observed only in postoperative PIAs in the high-dose BoNT-A group between all 4 rat-groups with experimentally created postoperative PIAs. In this study, high-dose BoNT-A is determined to be an effective agent in preventing postoperative PIAs. PMID:28706891

Assessment of drug-drug interaction potential between ceritinib and proton pump inhibitors in healthy subjects and in patients with ALK-positive non-small cell lung cancer.

PubMed

Lau, Yvonne Y; Gu, Wen; Lin, Tiffany; Viraswami-Appanna, Kalyanee; Cai, Can; Scott, Jeffrey W; Shi, Michael

2017-06-01

The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (C trough,ss ) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC 0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study. In the healthy subject study, co-administration of a single 750 mg dose of ceritinib with esomeprazole 40 mg for 6 days decreased ceritinib AUC 0-∞ by 76% and C max by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss and ORR regardless of concomitant PPI usage. Based on analysis 2, co-administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients suggested less effect on ceritinib exposure than that observed in healthy subjects as AUC 0-24h decreased by 30% and C max decreased by 25%. No clinically meaningful effect on steady-state exposure was observed after daily dosing. Long-term administration of ceritinib with PPIs does not adversely affect the PK and efficacy of ceritinib in ALK-positive cancer patients.

Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

PubMed

Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

2011-01-01

Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model.

PubMed

Xie, Ling; Zhong, Xiaohong; Liu, Dongbo; Liu, Lin; Xia, Zhilan

2017-12-01

Conventional scientific studies had supported the use of polysaccharides and β-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-β1 (TGF-β1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4 + CD25 + Foxp3 + (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P < 0.01). The application of middle- and high-dose FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid-related orphan receptor gamma t(RORγt) mRNA. High-dose FDPGLM possibly plays a role in ROU by promoting CD4 + CD25 + Foxp3 + Treg and inhibiting T helper cell 17 differentiation. This study also shows that FDPGLM may be potentially used as a complementary and alternative medicine treatment scheme for ROU.

Evaluation of Epidemiology and Animal Data for Risk Assessment: Chlorpyrifos Developmental Neurobehavioral Outcomes

PubMed Central

Li, Abby A.; Lowe, Kimberly A.; McIntosh, Laura J.; Mink, Pamela J.

2012-01-01

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring. PMID:22401178

Long-term effects of in utero and lactational exposure to butyl paraben in female rats.

PubMed

Guerra, Marina Trevizan; Sanabria, Marciana; Cagliarani, Stephannie Vieira; Leite, Gabriel Adan Araújo; Borges, Cibele Dos Santos; De Grava Kempinas, Wilma

2017-03-01

Parabens are used as preservatives in cosmetic, pharmaceutical, and food industries, and are frequently detected as contaminants in human fluids and tissues. The endocrine disrupting effects of parabens in female rodents include uterotrophic response, steroidogenesis impairment, and ovarian disturbances. The objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on female sexual development. Pregnant Wistar rats were treated subcutaneously with either corn oil or BP at doses of 10, 100, or 200 mg/kg, from gestational day (GD) 12 until GD 20 for female foetal gonad evaluation, and from GD 12 until the end of lactation to evaluate sexual parameters on the female offspring. Immature female rats were also used in the uterotrophic assay to evaluate the possible estrogenic action of parabens. Our results revealed that, in this experimental protocol, BP did not show estrogenic activity at the doses used and did not impair sexual development and fertility capacity in the female rats, but impaired sexual behavior. We conclude that brain sexual development may be more sensitive to BP effects and we speculate that doses higher than 100 mg/kg (the male lowest observed adverse effect level (LOAEL) for rodent reproductive parameters) would be necessary to promote damages in the female reproduction, regarding the same protocol of exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 776-788, 2017. © 2016 Wiley Periodicals, Inc.

Guidance on radiation dose limits for the lens of the eye: overview of the recommendations in NCRP Commentary No. 26.

PubMed

Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Donald; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A

2017-10-01

This review summarizes the conclusions and recommendations of the new National Council on Radiation Protection and Measurements (NCRP) Commentary No. 26 guidance on radiation dose limits for the lens of the eye. The NCRP addressed radiation protection principles in respect to the lens of the eye, discussed the current understanding of eye biology and lens effects, reviewed and evaluated epidemiology, and assessed exposed populations with the potential for significant radiation exposures to the lens while suggesting monitoring and protection practices. Radiation-induced damage to the lens of the eye can include the loss of clarity resulting in opacification or clouding several years after exposure. The impact is highly dependent on the type of radiation, how the exposure of the lens was delivered, the genetic susceptibilities of the individual exposed, and the location of the opacity relative to the visual axis of the individual. The preponderance of epidemiological evidence suggests that lens damage could occur at lower doses than previously considered and the NCRP has determined that it is prudent to reduce the recommended annual lens of the eye occupational dose limit from an equivalent dose of 150 mSv to an absorbed dose of 50 mGy. Significant additional research is still needed in the following areas: comprehensive evaluation of the overall effects of ionizing radiation on the eye, dosimetry methodology and dose-sparing optimization techniques, additional high quality epidemiology studies, and a basic understanding of the mechanisms of cataract development.

Sperm quality and fertility of boar seminal doses after 2 days of storage: does the type of extender really matter?

PubMed

Pinart, Elisabeth; Yeste, Marc; Prieto-Martínez, Noelia; Reixach, Josep; Bonet, Sergi

2015-06-01

The present approach was designed to evaluate the extender effects on sperm quality and fertility of short-term refrigerated seminal doses from Landrace boars lodged in husbandry-controlled conditions. For this purpose, we analyzed the sperm quality of seminal doses diluted in short-term (Beltsville Thawing Solution) and extra-long-term (Duragen) extenders from Days 0 to 2 of storage at 17 °C during an 8-month period. Pregnancy rates and litter size were evaluated from double inseminations within an interval of 12 hours (36 and 48 hours of refrigeration) of multiparous females using seminal doses diluted in each extender type. Sperm quality was assessed from the analyses of sperm motility and kinetics, sperm viability, expressed as plasma and acrosome membrane integrity, membrane lipid disorder, intracellular calcium levels, and acrosin activity. Results indicated significant differences between the extenders in the sperm quality of seminal doses. Therefore, the seminal doses diluted in Duragen had higher percentages of progressive motile spermatozoa and membrane-intact spermatozoa than those diluted in Beltsville Thawing Solution throughout all the experimental months. Nevertheless, despite these differences in preserving the sperm quality, pregnancy rates (>90%) and litter sizes (>10 piglets born per litter) were similar between the extenders. Our results had great relevance from a practical point of view because they reported lack of an extender effect on the reproductive performance of seminal doses during short-tem storage. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-F-T-174: Patient-Specific Point Dose Measurement Using Fiber Optic Radiation Sensor Using Cerenkov Radiation for Proton Therapeutic Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, J; National Cancer Center, Goyang-si; Kim, M

Purpose: A fiber-optic radiation sensor using Cerenkov radiation (FOCR) has been widely studied for use as a dosimeter for proton therapeutic beam. We developed the FOCR, and it applied to patient-specific point dose measurement in order to evaluate the effectiveness of the FOCR system for proton therapy QA. Methods: Calibration of FOCR was performed with an ionization chamber whose absolute doses were determined according to the IAEA TRS-398 protocol. To determine the calibration curve, the FOCR was irradiated perpendicularly to the proton beam at the 13 dose levels steps. We selected five actual patient treatment plans performed at proton therapymore » center and compared the resulting FOCR measurements with the ionization chamber measurements. Results: The Cerenkov light yield of the FOCR increases linearly with as the dose measured using the ionization chamber increases from 0 cGy to 500 cGy. The results indicate that the fitting curve is linear, suggesting that dose measurement based on the light yield of the FOCR is possible. The results of proton radiation dose QA performed using the FOCR for 10 proton fields and five patients are good agreement with an ionization chamber. Conclusion: We carried out the patient QA using the FOCR for proton therapeutic beam and evaluated the effectiveness of the FOCR as a proton therapy QA tool. Our results indicate that the FOCR is suitable for use in patient QA of clinical proton beams.« less

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

PubMed

Hung, Ching-Hsia; Shieh, Ja-Ping; Chiu, Chong-Chi; Wang, Jhi-Joung; Chen, Yu-Wen

2018-06-01

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED 50 )), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED 25 , ED 50 and ED 75 ), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Influence of Ultra-Low-Dose and Iterative Reconstructions on the Visualization of Orbital Soft Tissues on Maxillofacial CT.

PubMed

Widmann, G; Juranek, D; Waldenberger, F; Schullian, P; Dennhardt, A; Hoermann, R; Steurer, M; Gassner, E-M; Puelacher, W

2017-08-01

Dose reduction on CT scans for surgical planning and postoperative evaluation of midface and orbital fractures is an important concern. The purpose of this study was to evaluate the variability of various low-dose and iterative reconstruction techniques on the visualization of orbital soft tissues. Contrast-to-noise ratios of the optic nerve and inferior rectus muscle and subjective scores of a human cadaver were calculated from CT with a reference dose protocol (CT dose index volume = 36.69 mGy) and a subsequent series of low-dose protocols (LDPs I-4: CT dose index volume = 4.18, 2.64, 0.99, and 0.53 mGy) with filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR)-50, ASIR-100, and model-based iterative reconstruction. The Dunn Multiple Comparison Test was used to compare each combination of protocols (α = .05). Compared with the reference dose protocol with FBP, the following statistically significant differences in contrast-to-noise ratios were shown (all, P ≤ .012) for the following: 1) optic nerve: LDP-I with FBP; LDP-II with FBP and ASIR-50; LDP-III with FBP, ASIR-50, and ASIR-100; and LDP-IV with FBP, ASIR-50, and ASIR-100; and 2) inferior rectus muscle: LDP-II with FBP, LDP-III with FBP and ASIR-50, and LDP-IV with FBP, ASIR-50, and ASIR-100. Model-based iterative reconstruction showed the best contrast-to-noise ratio in all images and provided similar subjective scores for LDP-II. ASIR-50 had no remarkable effect, and ASIR-100, a small effect on subjective scores. Compared with a reference dose protocol with FBP, model-based iterative reconstruction may show similar diagnostic visibility of orbital soft tissues at a CT dose index volume of 2.64 mGy. Low-dose technology and iterative reconstruction technology may redefine current reference dose levels in maxillofacial CT. © 2017 by American Journal of Neuroradiology.

Single and short-term dosing effects of levocetirizine on adenosine monophosphate bronchoprovocation in atopic asthma

PubMed Central

Lee, Daniel K C; Gray, Robert D; Wilson, Andrew M; Robb, Fiona M; Soutar, Patricia C; Lipworth, Brian J

2004-01-01

Aims Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levocetirizine, given at the usual clinically recommended dose, on the primary outcome of AMP bronchoprovocation. Methods Fifteen atopic asthmatics were randomized in double-blind, cross-over fashion to receive for 1 week either levocetirizine 5 mg or placebo. There was a 1-week washout period prior to each randomized treatment. The provocative concentration of AMP producing a 20% fall in FEV1 (PC20) was measured after each washout at baseline and at 4–6 h following the first and last doses of each randomized treatment. Results Baseline mean ± SEM values after washout prior to each randomized treatment comparing levocetirizine vs placebo were not significantly different for prechallenge FEV1 (% predicted) 83 ± 4 vs 82 ± 4, or AMP PC20 (mg ml−1) 45 ± 24 vs 45 ± 22, respectively. Airway calibre as prechallenge FEV1 for levocetirizine vs placebo was not significantly different following the first dose 86 ± 4 vs 82 ± 4, or the last dose 85 ± 4 vs 83 ± 4, respectively. There were significant improvements (P< 0.05) in AMP PC20 comparing levocetirizine vs placebo following the first dose 123 ± 73 vs 48 ± 24, a 1.4 doubling dilution difference (95% CI 0.8, 1.9), and the last dose 127 ± 74 vs 53 ± 29, a 1.2 doubling dilution difference (95% CI 0.5, 2.0). AMP PC20 was also improved (P< 0.05) by the first and last doses of levocetirizine but not placebo, vs respective baseline values, with there being no difference in the degree of protection between first and last doses. Conclusions Single and short-term dosing with levocetirizine conferred similar improvements in bronchial hyper-responsiveness to AMP challenge, which was unrelated to prechallenge airway calibre. Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations. PMID:15206990

Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions

PubMed Central

Shim, Grace; Normil, Marie Delna; Testard, Isabelle; Hempel, William M.; Ricoul, Michelle; Sabatier, Laure

2016-01-01

Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)-induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere/centromere-fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR-induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term “relative dose effect” (RDE). This ratio is advantageous, as it allows for simple comparison of dose–response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2–15 Gy), to represent hypo- and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy. PMID:27379201

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

PubMed

Wu, Benjamin M; Sabarinath, Sreedharan N; Rand, Kenneth; Johnson, Judith; Derendorf, Hartmut

2011-06-01

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 μg/mL pre dose to 4 μg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

PubMed Central

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-01-01

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats. PMID:28430136

SU-E-T-378: Evaluation of An Analytical Model for the Inter-Seed Attenuation Effect in 103-Pd Multi-Seed Implant Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safigholi, H; Soliman, A; Song, W

Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summedmore » using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.« less

Patient- and cohort-specific dose and risk estimation for abdominopelvic CT: a study based on 100 patients

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Samei, Ehsan

2012-03-01

The purpose of this work was twofold: (a) to estimate patient- and cohort-specific radiation dose and cancer risk index for abdominopelvic computer tomography (CT) scans; (b) to evaluate the effects of patient anatomical characteristics (size, age, and gender) and CT scanner model on dose and risk conversion coefficients. The study included 100 patient models (42 pediatric models, 58 adult models) and multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which DLP-normalized-effective dose (k factor) and DLP-normalized-risk index values (q factor) were derived. The k factor showed exponential decrease with increasing patient size. For a given gender, q factor showed exponential decrease with both increasing patient size and patient age. The discrepancies in k and q factors across scanners were on average 8% and 15%, respectively. This study demonstrates the feasibility of estimating patient-specific organ dose and cohort-specific effective dose and risk index in abdominopelvic CT requiring only the knowledge of patient size, gender, and age.

Modulatory effects of naringin on hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetes in rats.

PubMed

Pari, Leelavinothan; Chandramohan, Ramasamy

2017-07-01

We evaluated the modulatory effects of naringin on altered hepatic key enzymes of carbohydrate metabolism in high-fat diet/low-dose streptozotocin-induced diabetic rats. Oral treatment of naringin at a doses of 20, 40 and 80 mg/kg body weight to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, blood glycosylated hemoglobin and increase in the levels of plasma insulin and blood hemoglobin. The altered activities of the hepatic key enzymes of carbohydrate metabolism such as hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase, glycogen phosphorylase and glycogen content of diabetic rats were significantly reverted to near normal levels by the treatment of naringin in a dose-dependent manner. Naringin at a dose of 80 mg/kg body weight showed the highest significant effect than the other two doses (20 and 40 mg/kg). Further, immunohistochemical observation of pancreas revealed that naringin-treated diabetic rats showed the increased number of insulin immunoreactive β-cells, which confirmed the biochemical findings. These findings revealed that naringin has potential antihyperglycemic activity in high-fat diet/low-dose streptozotocin-induced diabetic rats.

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

NASA Technical Reports Server (NTRS)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing radiation.

Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent values of the effective dose for external photons

NASA Astrophysics Data System (ADS)

Lee, Choonsik; Lee, Choonik; Han, Eun Young; Bolch, Wesley E.

2007-01-01

The effective dose recommended by the International Commission on Radiological Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding tissue weighting factors, wT. ICRP is in the process of revising its 1990 recommendations on the effective dose where new values of organs and tissue weighting factors have been proposed and published in draft form for consultation by the radiological protection community. In its 5 June 2006 draft recommendations, new organs and tissues have been introduced in the effective dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL) phantom series (e.g., salivary glands). Recently, the investigators at University of Florida have updated the series of ORNL phantoms by implementing new organ models and adopting organ-specific elemental composition and densities. In this study, the effective dose changes caused by the transition from the current recommendation of ICRP Publication 60 to the 2006 draft recommendations were investigated for external photon irradiation across the range of ICRP reference ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left-lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ-absorbed doses were calculated by implementing the revised ORNL phantoms in the Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were calculated under the 1990 and draft 2006 evaluation schemes of the ICRP. Effective doses calculated under the 2006 draft scheme were slightly higher than estimated under ICRP Publication 60 methods for all irradiation geometries exclusive of the AP geometry where an opposite trend was observed. The effective doses of the adult phantom were more greatly affected by the change in tissue weighting factors than that seen within the paediatric members of the phantom series. Additionally, dose conversion coefficients for newly identified radiosensitive organs—salivary glands, gall bladder, heart and prostate—were reported, as well as the brain, which was originally considered in ICRP Publication 60 as a member of the remainder category of the effective dose.

SU-F-T-380: Comparing the Effect of Respiration On Dose Distribution Between Conventional Tangent Pair and IMRT Techniques for Adjuvant Radiotherapy in Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, M; Ramaseshan, R

2016-06-15

Purpose: In this project, we compared the conventional tangent pair technique to IMRT technique by analyzing the dose distribution. We also investigated the effect of respiration on planning target volume (PTV) dose coverage in both techniques. Methods: In order to implement IMRT technique a template based planning protocol, dose constrains and treatment process was developed. Two open fields with optimized field weights were combined with two beamlet optimization fields in IMRT plans. We compared the dose distribution between standard tangential pair and IMRT. The improvement in dose distribution was measured by parameters such as conformity index, homogeneity index and coveragemore » index. Another end point was the IMRT technique will reduce the planning time for staff. The effect of patient’s respiration on dose distribution was also estimated. The four dimensional computed tomography (4DCT) for different phase of breathing cycle was used to evaluate the effect of respiration on IMRT planned dose distribution. Results: We have accumulated 10 patients that acquired 4DCT and planned by both techniques. Based on the preliminary analysis, the dose distribution in IMRT technique was better than conventional tangent pair technique. Furthermore, the effect of respiration in IMRT plan was not significant as evident from the 95% isodose line coverage of PTV drawn on all phases of 4DCT. Conclusion: Based on the 4DCT images, the breathing effect on dose distribution was smaller than what we expected. We suspect that there are two reasons. First, the PTV movement due to respiration was not significant. It might be because we used a tilted breast board to setup patients. Second, the open fields with optimized field weights in IMRT technique might reduce the breathing effect on dose distribution. A further investigation is necessary.« less

Magnetic-field-induced dose effects in MR-guided radiotherapy systems: dependence on the magnetic field strength.

PubMed

Raaijmakers, A J E; Raaymakers, B W; Lagendijk, J J W

2008-02-21

Several institutes are currently working on the development of a radiotherapy treatment system with online MR imaging (MRI) modality. The main difference between their designs is the magnetic field strength of the MRI system. While we have chosen a 1.5 Tesla (T) magnetic field strength, the Cross Cancer Institute in Edmonton will be using a 0.2 T MRI scanner and the company Viewray aims to use 0.3 T. The magnetic field strength will affect the severity of magnetic field dose effects, such as the electron return effect (ERE): considerable dose increase at tissue air boundaries due to returning electrons. This paper has investigated how the ERE dose increase depends on the magnetic field strength. Therefore, four situations where the ERE occurs have been simulated: ERE at the distal side of the beam, the lateral ERE, ERE in cylindrical air cavities and ERE in the lungs. The magnetic field comparison values were 0.2, 0.75, 1.5 and 3 T. Results show that, in general, magnetic field dose effects are reduced at lower magnetic field strengths. At the distal side, the ERE dose increase is largest for B = 0.75 T and depends on the irradiation field size for B = 0.2 T. The lateral ERE is strongest for B = 3 T but shows no effect for B = 0.2 T. Around cylindrical air cavities, dose inhomogeneities disappear if the radius of the cavity becomes small relative to the in-air radius of the secondary electron trajectories. At larger cavities (r > 1 cm), dose inhomogeneities exist for all magnetic field strengths. In water-lung-water phantoms, the ERE dose increase takes place at the water-lung transition and the dose decreases at the lung-water transition, but these effects are minimal for B = 0.2 T. These results will contribute to evaluating the trade-off between magnetic field dose effects and image quality of MR-guided radiotherapy systems.

Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

PubMed

Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

2015-02-01

The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

Long-term fate of depleted uranium at Aberdeen and Yuma Proving Grounds: Human health and ecological risk assessments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebinger, M.H.; Beckman, R.J.; Myers, O.B.

1996-09-01

The purpose of this study was to evaluate the immediate and long-term consequences of depleted uranium (DU) in the environment at Aberdeen Proving Ground (APG) and Yuma Proving Ground (YPG) for the Test and Evaluation Command (TECOM) of the US Army. Specifically, we examined the potential for adverse radiological and toxicological effects to humans and ecosystems caused by exposure to DU at both installations. We developed contaminant transport models of aquatic and terrestrial ecosystems at APG and terrestrial ecosystems at YPG to assess potential adverse effects from DU exposure. Sensitivity and uncertainty analyses of the initial models showed the portionsmore » of the models that most influenced predicted DU concentrations, and the results of the sensitivity analyses were fundamental tools in designing field sampling campaigns at both installations. Results of uranium (U) isotope analyses of field samples provided data to evaluate the source of U in the environment and the toxicological and radiological doses to different ecosystem components and to humans. Probabilistic doses were estimated from the field data, and DU was identified in several components of the food chain at APG and YPG. Dose estimates from APG data indicated that U or DU uptake was insufficient to cause adverse toxicological or radiological effects. Dose estimates from YPG data indicated that U or DU uptake is insufficient to cause radiological effects in ecosystem components or in humans, but toxicological effects in small mammals (e.g., kangaroo rats and pocket mice) may occur from U or DU ingestion. The results of this study were used to modify environmental radiation monitoring plans at APG and YPG to ensure collection of adequate data for ongoing ecological and human health risk assessments.« less

Dual Therapeutic Effects of C-10068, a Dextromethorphan Derivative, Against Post-Traumatic Nonconvulsive Seizures and Neuroinflammation in a Rat Model of Penetrating Ballistic-Like Brain Injury.

PubMed

Lu, Xi-Chun May; Shear, Deborah A; Graham, Philip B; Bridson, Gary W; Uttamsingh, Vinita; Chen, Zhiyong; Leung, Lai Yee; Tortella, Frank C

2015-10-15

Post-traumatic seizures can exacerbate injurious outcomes of severe brain trauma, yet effective treatments are limited owing to the complexity of the pathology underlying the concomitant occurrence of both events. In this study, we tested C-10068, a novel deuterium-containing analog of (+)-N-methyl-3-ethoxymorphinan, in a rat model of penetrating ballistic-like brain injury (PBBI) and evaluated the effects of C-10068 on PBBI-induced nonconvulsive seizures (NCS), acute neuroinflammation, and neurofunctional outcomes. NCS were detected by electroencephalographic monitoring. Neuroinflammation was evaluated by immunohistochemical markers, for example, glial fibrillary acidic protein and major histocompatibility complex class I, for activation of astrocytes and microglia, respectively. Neurofunction was tested using rotarod and Morris water maze tasks. Three infusion doses of C-10068 (1.0, 2.5, and 5.0 mg/kg/h × 72 h) were tested in the antiseizure study. Neuroinflammation and neurofunction were evaluated in animals treated with 5.0 mg/kg/h × 72 h C-10068. Compared to vehicle treatment, C-10068 dose dependently reduced PBBI-induced NCS incidence (40-50%), frequency (20-70%), and duration (30-82%). The most effective antiseizure dose of C-10068 (5.0 mg/kg/h × 72 h) also significantly attenuated hippocampal astrocyte activation and perilesional microglial reactivity post-PBBI. Within C-10068-treated animals, a positive correlation was observed in reduction in NCS frequency and reduction in hippocampal astrocyte activation. Further, C-10068 treatment significantly attenuated astrocyte activation in seizure-free animals. However, C-10068 failed to improve PBBI-induced motor and cognitive functions with the dosing regimen used in this study. Overall, the results indicating that C-10068 exerts both potent antiseizure and antiinflammatory effects are promising and warrant further investigation.

Dose dependent sun protective effect of topical melatonin: A randomized, placebo-controlled, double-blind study.

PubMed

Scheuer, Cecilie; Pommergaard, Hans-Christian; Rosenberg, Jacob; Gögenur, Ismail

2016-11-01

Ultraviolet radiation (UVR) by sunlight results in an increasing number of skin conditions. Earlier studies have suggested a protective effect of topical treatment with the pineal hormone melatonin. However, this protective effect has never been evaluated in natural sunlight, and the optimal dosing has not been clarified. The aim of this study was to investigate the sun protective effect of topical treatment with three different doses of melatonin (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight. The study was a randomized, placebo-controlled, double-blind study in healthy volunteers. Twenty-three healthy volunteers, 8 male and 15 female, were enrolled. The protective effect of three different doses of melatonin cream (0.5%, 2.5%, 12.5%) against erythema induced by natural sunlight was tested. All participants had their backs exposed to sun from 1:22 PM to 2:02 PM local time and UV-index was 9. Primary outcome was reduction in erythema evaluated by chromatography after sun exposure, when treated with topical melatonin cream (0.5%, 2.5%, 12.5%) versus placebo and no treatment. The erythema reaction was evaluated with chromatography and visual scoring at baseline, one, four, eight and 24h after exposure. Significant difference in erythema formation was found between areas treated with melatonin cream 12.5% and areas receiving placebo or no treatment (repeated measures ANOVA p=0.001). No differences were found between placebo and the 0.5% and 2.5% concentrations. Application of melatonin cream 12.5% protects against natural sunlight induced erythema. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, B; Medin, P

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 ofmore » 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).« less

SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, C; Schultheiss, T

Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

Improving contraceptive choice: fidelity of implementation and the gap between effectiveness and efficacy.

PubMed

Garbers, Samantha; Flandrick, Kathleen; Bermudez, Dayana; Meserve, Allison; Chiasson, Mary Ann

2014-11-01

Interventions to reduce unintended pregnancy through improved contraceptive use are a public health priority. A comprehensive process evaluation of a contraceptive assessment module intervention with demonstrated efficacy was undertaken. The 12-month process evaluation goal was to describe the extent to which the intervention was implemented as intended over time, and to identify programmatic adjustments to improve implementation fidelity. Quantitative and qualitative methods included staff surveys, electronic health record data, usage monitoring, and observations. Fidelity of implementation was low overall (<10% of eligible patients completed the entire module [dose received]). Although a midcourse correction making the module available in clinical areas led to increased dose delivered (23% vs. 30%, chi-square test p = .006), dose received did not increase significantly after this adjustment. Contextual factors including competing organizational and staff priorities and staff buy-in limited the level of implementation and precluded adoption of some strategies such as adjusting patient flow. Using a process evaluation framework enabled the research team to identify and address complexities inherent in effectiveness studies and facilitated the alignment of program and context. © 2014 Society for Public Health Education.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects.

PubMed

Griffiths, Roland R; Johnson, Matthew W; Richards, William A; Richards, Brian D; McCann, Una; Jesse, Robert

2011-12-01

This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions. Participants were 18 adults (17 hallucinogen-naïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up. Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects. Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

The effect of sibutramine, a serotonin-norepinephrine reuptake inhibitor, on platelets and fibrin networks of male Sprague-Dawley rats: a descriptive study.

PubMed

van der Schoor, Ciska; Oberholzer, Hester Magdalena; Bester, Megan Jean; van Rooy, Mia-Jeanne

2014-12-01

Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.

The effect of single and repeated UVB radiation on rabbit cornea.

PubMed

Fris, Miroslav; Tessem, May-Britt; Cejková, Jitka; Midelfart, Anna

2006-12-01

Cumulative effect of ultraviolet radiation (UVR) is an important aspect of UV corneal damage. The purpose of this study was to apply high resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR) spectroscopy to evaluate the effect of single and repeated UV radiation exposure of the same overall dose on the rabbit cornea. Corneal surfaces of 24 normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the first group (UVB1), animals were irradiated with a single dose (3.12 J/cm2; 21 min) of UVB radiation. The animals in the second group (UVB2) were irradiated three times for 7 min every other day (dose of 1.04 J/cm2; days 1, 3, 5) to give the same overall dose (3.12 J/cm2). The third group served as an untreated control group. One day after the last irradiation, the animals were sacrificed, and the corneas were removed and frozen. HR-MAS 1H NMR spectra from intact corneas were obtained. Special grouping patterns among the tissue samples and the relative percentage changes in particular metabolite concentrations were evaluated using modern statistical methods (multivariate analysis, one-way ANOVA). The metabolic profile of both groups of UVB-irradiated samples was significantly different from the control corneas. Substantial decreases in taurine, hypo-taurine and choline-derivatives concentrations and substantial elevation in glucose and betaine levels were observed following the UVR exposure. There was no significant difference between the effect of a single and repeated UVB irradiation of the same overall dose. For the first time, the effects of single and repeated UVR doses on the metabolic profile of the rabbit cornea were analysed and compared. The combination of HR-MAS 1H NMR spectroscopy and modern statistical methods (multivariate analysis, one-way ANOVA) proved suitable to assess the overall view of the metabolic alterations in the rabbit corneal tissue following UVB radiation exposure.

Medical management with diazepam for electrical status epilepticus during slow wave sleep in children.

PubMed

Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman

2014-03-01

Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

PubMed

Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

2006-11-10

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

Committed effective dose determination in southern Brazilian cereal flours.

PubMed

Scheibel, V; Appoloni, C R

2013-01-01

The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in eight commercial samples of South-Brazilian cereal flours (soy, wheat, cornmeal, cassava, rye, oat, barley and rice flours). The radioactivity traces of (228)Th, (228)Ra, (226)Ra, (40)K, (7)Be and (137)Cs were measured by gamma-ray spectrometry employing an HPGe detector of 66 % relative efficiency. The efficiency curve has taken into account the differences in densities and chemical composition between the matrix and the certified sample. The highest concentration levels of (228)Th and (40)K were 3.5±0.4 and 1469±17 Bq kg(-1) for soy flour, respectively, within the 95 % confidence level. The lower limit of detection for (137)Cs ranged from 0.04 to 0.4 Bq kg(-1). The highest committed effective dose was 0.36 μSv.y(-1) for (228)Ra in cassava flour (adults). All committed effective doses determined at the present work were lower than the International Atomic Energy Agency dose limit of 1 mSv.y(-1), to the public exposure.

Sensory evaluation by gamma radiation effect on protein allergen of laying hen eggs

NASA Astrophysics Data System (ADS)

Harder, M. N. C.; Arthur, V.; Perina, V. C. S.; Silva, L. C. A. S.; Bortoleto, G. G.

2012-08-01

Although considered the most complete food and nutritionally shown to be part of a healthy diet, the egg is the source of many eating disorders, especially for infants. Irradiation has been used in studies not only as a means of microbiological control, but also on its structural action in the substances molecules and has been used to reduce the allergenic effects. The aim of this study was to evaluate the sensory effects of Co60 gamma radiation on proteins, enabling the acceptability of allergy food for genetically intolerant people. Eggs commercial fresh and freeze-dried and subjected to gamma irradiation by Co60 source at doses 0 (control), 10 kGy; 20 kGy and 30 kGy and rates of doses of 19.4 kGy/h and 31.8 kGy/h. Acceptability test was used by the hedonic scale, since it is necessary to know the "affective status" of consumers for the product, implying a preference, i.e. the most preferred samples are the most accepted and vice versa. The samples were presented as the habit of consumption (cooked) to a group of 41 adults panelists of both gender, aged from 21 to 40 years, and served under complete block design balanced with respect to the order of presentation. The evaluated attributes was flavor, appearance and overall acceptability. In general, for boiled eggs and freeze-dried, it was observed that the control sample was the most acceptable, followed by the sample irradiated with 10 kGy in both dose rates. In addition, panelists presented in testimony that they found interesting changes due to irradiation; also said they would not buy the product because of the marked change in appearance and smell, which at one point he ended up in disgust and detract from sales of the product, but they would buy irradiated with 10 kGy in both dose rate and dose of 20 kGy at a dose rate of 19.4 kGy/h.

Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Stefano, Eduardo Jose; Vendito Soares, Francisco

2011-07-15

Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Groupmore » 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.« less

Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests.

PubMed

Haj-Mirzaian, Arya; Kordjazy, Nastaran; Haj-Mirzaian, Arvin; Ostadhadi, Sattar; Ghasemi, Mehdi; Amiri, Shayan; Faizi, Mehrdad; Dehpour, AhmadReza

2015-10-01

The antidepressant action of acute nicotine administration in clinical and animal studies is well recognized. But the underlying mechanism for this effect has not been carefully discovered. We attempted to evaluate the possible role of N-Methyl-D-aspartate (NMDA) receptors in the antidepressant-like effect of nicotine. After the assessment of locomotor activity in the open-field test, forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of nicotine in mice. We performed intraperitoneal administration of nicotine at different doses and periods before the tests. To assess the possible involvement of NMDA receptors, non-effective doses of NMDA antagonists and an NMDA agonist were obtained and were administered simultaneously with the non-effective and effective doses of nicotine, respectively. Nicotine (0.2 mg/kg, 30 min before FST/TST) significantly reduced the immobility time of mice similar to fluoxetine (20 mg/kg). Nicotine did not affect the locomotor behavior of mice in open-field test. Co-administration of non-effective doses of NMDA receptor antagonists, ketamine (1 or 0.3 mg/kg), MK-801 (0.05 or 0.005 mg/kg), and magnesium sulfate (10 or 5 mg/kg) with nicotine (0.1 or 0.03 mg/kg) had remarkable synergistic antidepressant effect in both FST and TST. Also, non-effective NMDA (75 or 30 mg/kg) reversed the anti-immobility effect of nicotine (0.2 mg/kg) on mouse FST and TST. Our study has for the first time confirmed that the antidepressant-like effect of nicotine on mice is NMDA-mediated, and nicotine presumably exerts this effect by antagonizing the glutamatergic NMDA receptors.

Evaluating the loudness of phantom auditory perception (tinnitus) in rats.

PubMed

Jastreboff, P J; Brennan, J F

1994-01-01

Using our behavioral paradigm for evaluating tinnitus, the loudness of salicylate-induced tinnitus was evaluated in 144 rats by comparing their behavioral responses induced by different doses of salicylate to those induced by different intensities of a continuous reference tone mimicking tinnitus. Group differences in resistance to extinction were linearly related to salicylate dose and, at moderate intensities, to the reference tone as well. Comparison of regression equations for salicylate versus tone effects permitted estimation of the loudness of salicylate-induced tinnitus. These results extend the animal model of tinnitus and provide evidence that the loudness of phantom auditory perception is expressed through observable behavior, can be evaluated, and its changes detected.

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies.

PubMed

Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

2014-06-01

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

Automated estimation of abdominal effective diameter for body size normalization of CT dose.

PubMed

Cheng, Phillip M

2013-06-01

Most CT dose data aggregation methods do not currently adjust dose values for patient size. This work proposes a simple heuristic for reliably computing an effective diameter of a patient from an abdominal CT image. Evaluation of this method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore scanners demonstrates close correspondence between computed and manually measured patient effective diameters, with a mean absolute error of 1.0 cm (error range +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60 patients on Siemens, General Electric, and Toshiba scanners. A calculated effective diameter in the middle slice of an abdominal CT study was found to be a close approximation of the mean calculated effective diameter for the study, with a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm). Furthermore, the mean absolute error for an adjusted mean volume computed tomography dose index (CTDIvol) using a mid-study calculated effective diameter, versus a mean per-slice adjusted CTDIvol based on the calculated effective diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These results are used to calculate approximate normalized dose length product values in an abdominal CT dose database of 12,506 studies.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

2014-04-01

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons.

PubMed

Kumar, Rajesh; Nyakundi, Ruth; Kariuki, Thomas; Ozwara, Hastings; Nyamongo, Onkoba; Mlambo, Godfree; Ellefsen, Barry; Hannaman, Drew; Kumar, Nirbhay

2013-06-28

Plasmodium falciparum Pfs25 antigen, expressed on the surface of zygotes and ookinetes, is one of the leading targets for the development of a malaria transmission-blocking vaccine (TBV). Our laboratory has been evaluating DNA plasmid based Pfs25 vaccine in mice and non-human primates. Previously, we established that in vivo electroporation (EP) delivery is an effective method to improve the immunogenicity of DNA vaccine encoding Pfs25 in mice. In order to optimize the in vivo EP procedure and test for its efficacy in more clinically relevant larger animal models, we employed in vivo EP to evaluate the immune response and protective efficacy of Pfs25 encoding DNA vaccine in nonhuman primates (olive baboons, Papio anubis). The results showed that at a dose of 2.5mg DNA vaccine, antibody responses were significantly enhanced with EP as compared to without EP resulting in effective transmission blocking efficiency. Similar immunogenicity enhancing effect of EP was also observed with lower doses (0.5mg and 1mg) of DNA plasmids. Further, final boosting with a single dose of recombinant Pfs25 protein resulted in dramatically enhanced antibody titers and significantly increased functional transmission blocking efficiency. Our study suggests priming with DNA vaccine via EP along with protein boost regimen as an effective method to elicit potent immunogenicity of malaria DNA vaccines in nonhuman primates and provides the basis for further evaluation in human volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

TOPIRAMATE’S EFFECTS ON COCAINE-INDUCED SUBJECTIVE MOOD, CRAVING, AND PREFERENCE FOR MONEY OVER DRUG TAKING

PubMed Central

Johnson, Bankole A.; Roache, John D.; Ait-Daoud, Nassima; Gunderson, Erik W.; Haughey, Heather M.; Wang, Xin-Qun; Liu, Lei

2012-01-01

Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine’s abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving, and preference for cocaine over money induced by low and high doses (0.325 and 0.650 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university inpatient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square crossover design in which 3 experimental challenge doses of low-dose cocaine, high-dose cocaine, and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pretreatments separated by a 1-week washout period (2006–2009). After placebo pretreatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine, and monetary value of cocaine in a behavioral preference test of cocaine vs. money choice. Topiramate pretreatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria, and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine’s abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate’s prominent sedative effects. PMID:23039088

Effective dose equivalent on the ninth Shuttle--Mir mission (STS-91)

NASA Technical Reports Server (NTRS)

Yasuda, H.; Badhwar, G. D.; Komiyama, T.; Fujitaka, K.

2000-01-01

Organ and tissue doses and effective dose equivalent were measured using a life-size human phantom on the ninth Shuttle-Mir Mission (STS-91, June 1998), a 9.8-day spaceflight at low-Earth orbit (about 400 km in altitude and 51.65 degrees in inclination). The doses were measured at 59 positions using a combination of thermoluminescent dosimeters of Mg(2)SiO(4):Tb (TDMS) and plastic nuclear track detectors (PNTD). In correcting the change in efficiency of the TDMS, it was assumed that reduction of efficiency is attributed predominantly to HZE particles with energy greater than 100 MeV nucleon(-1). A conservative calibration curve was chosen for determining LET from the PNTD track-formation sensitivities. The organ and tissue absorbed doses during the mission ranged from 1.7 to 2.7 mGy and varied by a factor of 1.6. The dose equivalent ranged from 3.4 to 5.2 mSv and varied by a factor of 1.5 on the basis of the dependence of Q on LET in the 1990 recommendations of the ICRP. The effective quality factor (Q(e)) varied from 1.7 to 2.4. The dose equivalents for several radiation-sensitive organs, such as the stomach, lung, gonad and breast, were not significantly different from the skin dose equivalent (H(skin)). The effective dose equivalent was evaluated as 4.1 mSv, which was about 90% of the H(skin).

Adding Dopamine to Proxymetacaine or Oxybuprocaine Solutions Potentiates and Prolongs the Cutaneous Antinociception in Rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Lin, Heng-Teng; Wang, Jhi-Joung; Hung, Ching-Hsia

2018-05-01

We evaluated the interaction of dopamine-proxymetacaine and dopamine- oxybuprocaine antinociception using isobolograms. This experiment uses subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under the skin of the rat's back, thus simulating infiltration blocks. The dose-related antinociceptive curves of proxymetacaine and oxybuprocaine alone and in combination with dopamine were constructed, and then the antinociceptive interactions between the local anesthetic and dopamine were analyzed using isobolograms. Subcutaneous proxymetacaine, oxybuprocaine, and dopamine produced a sensory block to local skin pinpricks in a dose-dependent fashion. The rank order of potency was proxymetacaine (0.57 [0.52-0.63] μmol/kg) > oxybuprocaine (1.05 [0.96-1.15] μmol/kg) > dopamine (165 [154-177] μmol/kg; P < .01 for each comparison) based on the 50% effective dose values. On the equianesthetic basis (25% effective dose, 50% effective dose, and 75% effective dose), the nociceptive block duration of proxymetacaine or oxybuprocaine was shorter than that of dopamine (P < .01). Oxybuprocaine or proxymetacaine coinjected with dopamine elicited a synergistic antinociceptive effect and extended the duration of action. Oxybuprocaine and proxymetacaine had a higher potency and provoked a shorter duration of sensory block compared with dopamine. The use of dopamine increased the quality and duration of skin antinociception caused by oxybuprocaine and proxymetacaine.

Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures

NASA Astrophysics Data System (ADS)

Mavroidis, Panayiotis; Costa Ferreira, Brigida; Shi, Chengyu; Lind, Bengt K.; Papanikolaou, Nikos

2007-07-01

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose ({\\bar{\\bar{D}}}) is applied together with the complication-free tumour control probability (P+). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using {\\bar{\\bar{D}}} as the common prescription point of the treatment plans and plotting the tissue response probabilities versus {\\bar{\\bar{D}}} for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome (P+ of 62.2% and 46.0%, {\\bar{\\bar{D}}} to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, {\\bar{\\bar{D}}} to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, {\\bar{\\bar{D}}} to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P_ +{-}{\\bar{\\bar{D}}} diagrams to effectively evaluate and compare treatment plans.

A Subanalgesic Dose of Morphine Eliminates Nalbuphine Anti-analgesia in Postoperative Pain

PubMed Central

Gear, Robert W.; Gordon, Newton C.; Hossaini-Zadeh, Mehran; Lee, Janice S.; Miaskowski, Christine; Paul, Steven M.; Levine, Jon D.

2008-01-01

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by co-administration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by co-administering a dose of morphine low enough that it does not produce analgesia. Following extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of two low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low dose morphine may act as an anti-analgesia opioid receptor antagonist. Perspective Previously we reported that the nalbuphine produces both analgesic and anti-analgesic effects, and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism. PMID:18201935

Systematic evaluation of four-dimensional hybrid depth scanning for carbon-ion lung therapy.

PubMed

Mori, Shinichiro; Furukawa, Takuji; Inaniwa, Taku; Zenklusen, Silvan; Nakao, Minoru; Shirai, Toshiyuki; Noda, Koji

2013-03-01

Irradiation of a moving target with a scanning beam requires a comprehensive understanding of organ motion as well as a robust dose error mitigation technique. The authors studied the effects of intrafractional respiratory motion for carbon-ion pencil beam scanning with phase-controlled rescanning on dose distributions for lung tumors. To address density variations, they used 4DCT data. Dose distributions for various rescanning methods, such as simple layer rescanning (LR), volumetric rescanning, and phase-controlled rescanning (PCR), were calculated for a lung phantom and a lung patient studies. To ensure realism, they set the scanning parameters such as scanning velocity and energy variation time to be similar to those used at our institution. Evaluation metrics were determined with regard to clinical relevance, and consisted of (i) phase-controlled rescanning, (ii) sweep direction, (iii) target motion (direction and amplitude), (iv) respiratory cycle, and (v) prescribed dose. Spot weight maps were calculated by using a beam field-specific target volume, which takes account of range variations for respective respiratory phases. To emphasize the impact of intrafractional motion on the dose distribution, respiratory gating was not used. The accumulated dose was calculated by applying a B-spline-based deformable image registration, and the results for phase-controlled layered rescanning (PCRL) and phase-controlled volumetric rescanning (PCRV) were compared. For the phantom study, simple LR was unable to improve the dose distributions for an increased number of rescannings. The phase-controlled technique without rescanning (1×PCRL and 1×PCRV) degraded dose conformity significantly due to a reduced scan velocity. In contrast, 4×PCRL or more significantly and consistently improved dose distribution. PCRV showed interference effects, but in general also improved dose homogeneity with higher numbers of rescannings. Dose distributions with single PCRL∕PCRV with a sweep direction perpendicular to motion direction showed large hot∕cold spots; however, this effect vanished with higher numbers of rescannings for both methods. Similar observations were obtained for the other dose metrics, such as target motion (SI∕AP), amplitude (6-22 mm peak-to-peak) and respiratory period (3.0-5.0 s). For four or more rescannings, both methods showed significantly better results, albeit that volumetric PCR was more affected by interference effects, which lead to severe degradation of a few dose distributions. The clinical example showed the same tendencies as the phantom study. Dose assessment metrics (D95, Dmax∕Dmin, homogeneity index) were improved with an increasing number of PCRL∕PCRV, but with PCRL being more robust. PCRL requires a longer treatment time than PCRV for high numbers of rescannings in the NIRS scanning system but is more robust. Although four or more rescans provided good dose homogeneity and conformity, the authors prefer to use more rescannings for clinical cases to further minimize dose degradation effects due to organ motion.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

PubMed

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marsh, R. M.; Silosky, M., E-mail: michael.silosky@ucdenver.edu

Purpose: The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. Methods: This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position themore » dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. Results: (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R{sup 2} = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o’clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. Conclusions: (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.« less

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits.

PubMed

Marsh, R M; Silosky, M

2015-04-01

The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position the dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R(2) = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o'clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials.

PubMed

Veettil, Sajesh K; Lim, Kean Ghee; Ching, Siew Mooi; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-11-14

Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established. Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA). In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal. Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

Time related neutralization of two doses acetyl salicylic acid.

PubMed

Aguejouf, O; Malfatti, E; Belon, P; Doutremepuich, C

2000-11-15

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis has become an important issue. In fact, hemorrhage complications are often associated with its use. On the other hand, previous studies showed unexpected thrombotic potencies associated with the presence of this drug at ultra low doses (ULD) in the circulation. In this study, we aimed to evaluate the effect of aspirin at ULD, injected 1, 2, or 3 hours after the administration of aspirin at 100 mg/kg, on hemostasis and bleeding in rats. We used an experimental model of thrombosis induced by laser beams to evaluate these effects. Platelet aggregation was determined by Cardinal and Flower method. Results from this investigation demonstrate that the neutralizing effect of aspirin at ULD did not operate significantly 1 hour after the injection of aspirin at 100 mg/kg. This effect was observed 2 and 3 hours after. The use of aspirin at ULD to neutralize the side effects of aspirin at high doses will reduce the hemorrhagic risk during extra corporeal circulation. The therapeutic benefit and safety of aspirin therapy in the treatment of cardiovascular diseases can be obtained.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Heng, E-mail: hengli@mdanderson.org; Zhu, X. Ronald; Zhang, Xiaodong

Purpose: To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials: The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results: Without delivery sequence optimization,more » the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions: Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients' breathing patterns.« less

Optimization of 64-MDCT urography: effect of dual-phase imaging with furosemide on collecting system opacification and radiation dose.

PubMed

Portnoy, Orith; Guranda, Larisa; Apter, Sara; Eiss, David; Amitai, Marianne Michal; Konen, Eli

2011-11-01

The purpose of this study was to compare opacification of the urinary collecting system and radiation dose associated with three-phase 64-MDCT urographic protocols and those associated with a split-bolus dual-phase protocol including furosemide. Images from 150 CT urographic examinations performed with three scanning protocols were retrospectively evaluated. Group A consisted of 50 sequentially registered patients who underwent a three-phase protocol with saline infusion. Group B consisted of 50 sequentially registered patients who underwent a reduced-radiation three-phase protocol with saline. Group C consisted of 50 sequentially registered patients who underwent a dual-phase split-bolus protocol that included a low-dose furosemide injection. Opacification of the urinary collecting system was evaluated with segmental binary scoring. Contrast artifacts were evaluated, and radiation doses were recorded. Results were compared by analysis of variance. A significant reduction in mean effective radiation dose was found between groups A and B (p < 0.001) and between groups B and C (p < 0.001), resulting in 65% reduction between groups A and C (p < 0.001). This reduction did not significantly affect opacification score in any of the 12 urinary segments (p = 0.079). In addition, dense contrast artifacts overlying the renal parenchyma observed with the three-phase protocols (groups A and B) were avoided with the dual-phase protocol (group C) (p < 0.001). A dual-phase protocol with furosemide injection is the preferable technique for CT urography. In comparison with commonly used three-phase protocols, the dual-phase protocol significantly reduces radiation exposure dose without reduction in image quality.

A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

PubMed

Gaudio, Carlo; Petriello, Gennaro; Pelliccia, Francesco; Tanzilli, Alessandra; Bandiera, Alberto; Tanzilli, Gaetano; Barillà, Francesco; Paravati, Vincenzo; Pellegrini, Massimo; Mangieri, Enrico; Barillari, Paolo

2018-05-08

Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.